alliance dissolution system operator's guide · 2008. 1. 29. · corriente alterna protective...

Waters AllianceDissolution System

Operator’s Guide

34 Maple StreetMilford, MA 01757

71500034302, Revision A

NOTICE

The information in this document is subject to change without notice and should not be construed as a commitment by Waters Corporation. Waters Corporation assumes no responsibility for any errors that may appear in this document. This document is believed to be complete and accurate at the time of publication. In no event shall Waters Corporation be liable for incidental or consequential damages in connection with, or arising from, the use of this document.

© 2001 WATERS CORPORATION. PRINTED IN THE UNITED STATES OF AMERICA. ALL RIGHTS RESERVED. THIS DOCUMENT OR PARTS THEREOF MAY NOT BE REPRODUCED IN ANY FORM WITHOUT THE WRITTEN PERMISSION OF THE PUBLISHER.

Alliance, Millennium, and Waters are registered trademarks, and PerformancePLUS, PowerStation, and SAT/IN are trademarks of Waters Corporation.

Acrodisk is a registered trademark of Paul Gelman Laboratory.

PEEK is a trademark of Victrex Corporation.

SR8-Plus and Uni-Probe are trademarks of Hanson Research, Inc.

VanKel is a trademark of VanKel Technology Group.

All other trademarks or registered trademarks are the sole property of their respective owners.

Note: When you use the instrument, follow generally accepted procedures for quality control and methods development.

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If you observe a change in the retention of a particular compound, in the resolution between two compounds, or in peak shape, immediately determine the reason for the changes. Until you determine the cause of a change, do not rely on the separation results.

Note: The Installation Category (Overvoltage Category) for this instrument is Level II. The Level II Category pertains to equipment that receives its electrical power from a local level, such as an electrical wall outlet.

STOPAttention: Changes or modifications to this unit not expressly approved by the party responsible for compliance could void the user’s authority to operate the equipment.

Important : Toute modification sur cette unité n’ayant pas été expressément approuvée par l’autorité responsable de la conformité à la réglementation peut annuler le droit de l’utilisateur à exploiter l’équipement.

Achtung: Jedwede Änderungen oder Modifikationen an dem Gerät ohne die ausdrückliche Genehmigung der für die ordnungsgemäße Funktionstüchtigkeit verantwortlichen Personen kann zum Entzug der Bedienungsbefugnis des Systems führen.

Avvertenza: eventuali modifiche o alterazioni apportate a questa unità e non espressamente approvate da un ente responsabile per la conformità annulleranno l’autorità dell’utente ad operare l’apparecchiatura.

Atención: cualquier cambio o modificación realizado a esta unidad que no haya sido expresamente aprobado por la parte responsable del cumplimiento puede anular la autorización de la que goza el usuario para utilizar el equipo.

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Caution: Use caution when working with any polymer tubing under pressure:• Always wear eye protection when near pressurized polymer tubing.

• Extinguish all nearby flames.

• Do not use Tefzel tubing that has been severely stressed or kinked.

• Do not use Tefzel tubing with tetrahydrofuran (THF) or concentrated nitric or sulfuric acids.

• Be aware that methylene chloride and dimethyl sulfoxide cause Tefzel tubing to swell, which greatly reduces the rupture pressure of the tubing.

Attention : soyez très prudent en travaillant avec des tuyaux de polymères sous pression :

• Portez toujours des lunettes de protection quand vous vous trouvez à proximité de tuyaux de polymères.

• Eteignez toutes les flammes se trouvant à proximité.

• N'utilisez pas de tuyau de Tefzel fortement abîmé ou déformé.

• N'utilisez pas de tuyau de Tefzel avec de l'acide sulfurique ou nitrique, ou du tétrahydrofurane (THT).

• Sachez que le chlorure de méthylène et le sulfoxyde de diméthyle peuvent provoquer le gonflement des tuyaux de Tefzel, diminuant ainsi fortement leur pression de rupture.

Vorsicht: Bei der Arbeit mit Polymerschläuchen unter Druck ist besondere Vorsicht angebracht:

• In der Nähe von unter Druck stehenden Polymerschläuchen stets Schutzbrille tragen.

• Alle offenen Flammen in der Nähe löschen.

• Keine Tefzel-Schläuche verwenden, die stark geknickt oder überbeansprucht sind.

• Tefzel-Schläuche nicht für Tetrahydrofuran (THF) oder konzentrierte Salpeter- oder Schwefelsäure verwenden.

• Durch Methylenchlorid und Dimethylsulfoxid können Tefzel-Schläuche quellen; dadurch wird der Berstdruck des Schlauches erheblich reduziert.

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Precauzione: prestare attenzione durante le operazioni con i tubi di polimero sotto pressione:• Indossare sempre occhiali da lavoro protettivi nei pressi di tubi di

polimero pressurizzati.

• Estinguere ogni fonte di ignizione circostante.

• Non utilizzare tubi Tefzel soggetti a sollecitazioni eccessive o incurvati.

• Non utilizzare tubi Tefzel contenenti tetraidrofurano (THF) o acido solforico o nitrico concentrato.

• Tenere presente che il cloruro di metilene e il dimetilsolfossido provocano rigonfiamento nei tubi Tefzel, che riducono notevolmente il limite di pressione di rottura dei tubi stessi.

Advertencia: manipular con precaución los tubos de polimero bajo presión:• Protegerse siempre los ojos a proximidad de tubos de polimero bajo

presión.

• Apagar todas las llamas que estén a proximidad.

• No utilizar tubos Tefzel que hayan sufrido tensiones extremas o hayan sido doblados.

• No utilizar tubos Tefzel con tetrahidrofurano o ácidos nítrico o sulfúrico concentrados.

• No olvidar que el cloruro de metileno y el óxido de azufre dimetilo inflan los tubos Tefzel lo que reduce en gran medida la presión de ruptura de los tubos.

Caution: The user shall be made aware that if the equipment is used in a manner not specified by the manufacturer, the protection provided by the equipment may be impaired.

Attention : L’utilisateur doit être informé que si le matériel est utilisé d’une façon non spécifiée par le fabricant, la protection assurée par le matériel risque d’être défectueuses.

Vorsicht: Der Benutzer wird darauf aufmerksam gemacht, dass bei unsachgemäßer Verwenddung des Gerätes unter Umständen nicht ordnungsgemäß funktionieren.

Precauzione: l’utente deve essere al corrente del fatto che, se l’apparecchiatura viene usta in un modo specificato dal produttore, la protezione fornita dall’apparecchiatura potrà essere invalidata.

Advertencia: El usuario deberá saber que si el equipo se utiliza de forma distinta a la especificada por el fabricante, las medidas de protección del equipo podrían ser insuficientes.

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Caution: To protect against fire hazard, replace fuses with those of the same type and rating.

Attention : Remplacez toujours les fusibles par d’autres du même type et de la même puissance afin d’éviter tout risque d’incendie.

Vorsicht: Zum Schutz gegen Feuergefahr die Sicherungen nur mit Sicherungen des gleichen Typs und Nennwertes ersetzen.

Precauzione: per una buona protezione contro i rischi di incendio, sostituire i fusibili con altri dello stesso tipo e amperaggio.

Precaución: sustituya los fusibles por otros del mismo tipo y características para evitar el riesgo de incendio.

Caution: To avoid possible electrical shock, power off the instrument and disconnect the power cord before servicing the instrument.

Attention : Afin d’éviter toute possibilité de commotion électrique, mettez hors tension l’instrument et débranchez le cordon d’alimentation de la prise avant d’effectuer la maintenance de l’instrument.

Vorsicht: Zur Vermeidung von Stromschlägen sollte das Gerät vor der Wartung abgeschaltet und vom Netz getrennt werden.

Precauzione: per evitare il rischio di scossa elettrica, spegnere lo strumento e scollegare il cavo di alimentazione prima di svolgere la manutenzione dello strumento.

Precaución: para evitar choques eléctricos, apague el instrumento y desenchufe el cable de alimentación antes de realizar cualquier reparación en el instrumento.

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Commonly Used Symbols

Direct currentCourant continuGleichstromCorrente continuaCorriente continua

Alternating currentCourant alternatifWechselstromCorrente alternataCorriente alterna

Protective conductor terminalBorne du conducteur de protectionSchutzleiteranschlussTerminale di conduttore con protezioneBorne del conductor de tierra

Frame or chassis terminalBorne du cadre ou du châssisRahmen- oder ChassisanschlussTerminale di struttura o telaioBorne de la estructura o del chasis

Caution or refer to manualAttention ou reportez-vous au guideVorsicht, oder lesen Sie das HandbuchPrestare attenzione o fare riferimento alla guidaActúe con precaución o consulte la guía

Caution, hot surface or high temperatureAttention, surface chaude ou température élevéeVorsicht, heiße Oberfläche oder hohe TemperaturPrecauzione, superficie calda o elevata temperaturaPrecaución, superficie caliente o temperatura elevada

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Caution, risk of electric shock (high voltage)Attention, risque de commotion électrique (haute tension)Vorsicht, Elektroschockgefahr (Hochspannung)Precauzione, rischio di scossa elettrica (alta tensione)Precaución, peligro de descarga eléctrica (alta tensión)

Caution, risk of needle-stick punctureAttention, risques de perforation de la taille d’une aiguilleVorsicht, Gefahr einer SpritzenpunktierungPrecauzione, rischio di puntura con agoPrecaución, riesgo de punción con aguja

Caution, ultraviolet lightAttention, rayonnement ultrvioletVorsicht, Ultraviolettes LichtPrecauzione, luce ultraviolettaPrecaución, emisiones de luz ultravioleta

Commonly Used Symbols (Continued)

UV

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Dissolution System Information

Intended Use

The Waters 2695 Dissolution Separations Module can be used for in-vitro diagnostic testing to analyze many compounds, including diagnostic indicators and therapeutically monitored compounds. When you develop methods, follow the “Protocol for the Adoption of Analytical Methods in the Clinical Chemistry Laboratory,” American Journal of Medical Technology, 44, 1, pages 30–37 (1978). This protocol covers good operating procedures and techniques necessary to validate system and method performance.

Biological Hazard

When you analyze physiological fluids, take all necessary precautions and treat all specimens as potentially infectious. Precautions are outlined in “CDC Guidelines on Specimen Handling,” CDC – NIH Manual, 1984.

Calibration

Follow acceptable methods of calibration with pure standards to calibrate methods. Use a minimum of five standards to generate a standard curve. The concentration range should cover the entire range of quality-control samples, typical specimens, and atypical specimens.

Quality Control

Routinely run three quality-control samples. Quality-control samples should represent subnormal, normal, and above-normal levels of a compound. Ensure that quality-control sample results are within an acceptable range, and evaluate precision from day to day and run to run. Data collected when quality-control samples are out of range may not be valid. Do not report this data until you ensure that chromatographic system performance is acceptable.

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Table of Contents

Preface ....................................................................................... 19

Chapter 1 Dissolution System Theory of Operation ......................................... 24

1.1 Dissolution Testing Overview ................................................ 24

1.2 Alliance Dissolution System Description............................... 25

1.2.2 Waters Transfer Module ............................................. 31

1.2.3 Detector ..................................................................... 33

1.2.4 Dissolution Test Station (Bath)................................... 33

1.2.5 Uni-Probe Assembly .................................................. 34

1.2.6 Electric Sampling Probes .......................................... 36

1.3 Principles of Operation.......................................................... 37

Chapter 2 Installing the Dissolution System ..................................................... 41

2.1 Site Selection and Power Requirements............................... 42

2.2 Unpacking and Inspecting..................................................... 44

2.3 Making Electrical Power Connections ................................... 45

2.3.2 Installing the Column Heater ..................................... 47

2.3.3 Connecting the Waters Transfer Module.................... 49

Chapter 3 Making Fluidic Connections ............................................................. 53

3.1 Overview ............................................................................... 54

3.2 Connecting the System Fluidics............................................ 56

10 Table of Contents

3.2.2 Connecting the 2695D Separations Module and the Transfer Module ......................................................... 57

3.2.3 Connecting the Waters Transfer Module and the Dissolution Bath Vessels ........................................... 60

3.2.4 Connecting the Uni-Probes........................................ 63

3.2.5 Connecting Electric Probes ....................................... 66

Chapter 4 Configuring Components ................................................................. 67

4.1 Operating Configurations ...................................................... 69

4.1.2 Connecting Components when the 2695D Separations Module is the System Controller................................ 75

4.1.3 Connecting Components when the Millennium³² Data System is the System Controller ............................... 76

4.1.4 Connecting to Generic Data Systems and to Generic Baths ......................................................................... 77

4.1.5 Using the busSAT/IN Module..................................... 77

4.2 Making RS-232 Serial Port Connections .............................. 78

4.2.2 Connecting Hanson SR8-Plus Baths to the Waters Transfer Module ......................................................... 79

4.2.3 Connecting Printers in the Alliance DissolutionSystem ...................................................................... 80

Chapter 5 Setting Up the Dissolution System .................................................. 81

5.1 Starting Up the Dissolution System ...................................... 81

5.2 Preparing for Dissolution Testing .......................................... 83

5.2.2 Setting Up the Waters Transfer Module ..................... 85

Table of Contents 11

5.2.3 Setting Up the Dissolution Test Bath ......................... 87

5.2.4 Setting Up the Detector ............................................. 88

5.2.5 Setting Up the Millennium³² Software ........................ 89

5.3 Developing a Dissolution Method.......................................... 89

5.3.2 Reviewing and Customizing Your Dissolution Method99

5.3.3 Sample Pooling........................................................ 103

5.3.4 Saving a Dissolution Method as a Sample Set........ 104

Chapter 6 Making a Run ................................................................................ 107

6.1 Running the Dissolution Test............................................... 107

6.1.2 Making a Run Using a Single-Bath System............. 109

6.1.3 Making a Run Using a Dual-Bath System ............... 110

6.1.4 Scanning for Required Vials .................................... 114

6.1.5 Applying Initial Conditions........................................ 116

6.1.6 Printing Dissolution Reports .................................... 117

6.2 Monitoring Dissolution System Status ................................ 119

6.2.2 Customizing the Status Screen Layout.................... 124

Chapter 7 Maintaining the Dissolution System ............................................... 126

7.1 Maintenance Considerations .............................................. 126

7.2 Routine Maintenance Procedures....................................... 127

7.2.2 Replacing Waters Transfer Module Syringes........... 128

7.2.3 Replacing the Transfer Module Fuse ....................... 131

7.2.4 Maintaining Other Parts of the Dissolution System . 132

12 Table of Contents

Chapter 8 Error Messages, Diagnostics, and Troubleshooting ....................... 136

8.1 Startup Diagnostics and Error Messages ........................... 136

8.1.2 Error Log.................................................................. 142

8.2 User-Initiated Diagnostics ................................................... 142

8.2.2 Performing Dissolution Diagnostics ......................... 144

8.2.3 Performing Transfer Module Diagnostics ................. 146

8.3 Troubleshooting................................................................... 147

8.3.2 Hardware Troubleshooting ....................................... 148

8.3.3 General Chromatography Troubleshooting .............. 150

Appendix A Dissolution System Specifications.................................................. 151

Appendix B Spare Parts..................................................................................... 152

Appendix C Solvent Considerations for a Dissolution System ........................... 154

Index ..................................................................................... 155

Table of Contents 13

List of Figures

1-1 Waters Alliance Dissolution System (Dual-Bath), Recommended Layout ............................................................................................ 27

1-2 Waters 2695D Separations Module with Column Heater .............. 281-3 Dissolution Dispenser .................................................................... 291-4 Dissolution Dispenser Needle Location and Fluidic Tubing

Color-Code Diagram...................................................................... 301-5 Waters Transfer Module (Eight-Syringe Model) ............................. 321-6 Uni-Probe with Check Valve Assembly .......................................... 351-7 Uni-Probe (no check valve) Assembly with Integrated Recirculation

Line Port ........................................................................................ 351-8 Uni-Probe (no check valve) Assembly and Discrete Recirculation

Line ................................................................................................ 361-9 Single-probe Configuration ............................................................ 371-10 Alliance Dissolution System Single-Bath Operation ...................... 381-11 Alliance Dissolution System Dual-Bath Operation......................... 39

2-1 Major Steps in Installing the Dissolution System ........................... 412-2 Waters Alliance Dissolution System Rear Panel Electrical

Connections................................................................................... 452-3 Waters 2695D Separations Module Dimensions (Column Heater

Attached) ....................................................................................... 472-4 2695D Separations Module Rear Panel Electrical Connections.... 482-5 Waters Transfer Module Dimensions ............................................. 502-6 Waters Transfer Module Rear Panel and Desktop Power Supply

Module ........................................................................................... 502-7 Waters Transfer Module Rear Panel Electrical Connections ......... 52

3-1 Waters Alliance Dissolution System Single-Bath Installation......... 553-2 Ferrule, Compression Screw, and Union Assembly

(Exploded View)............................................................................. 57

14 List of Figures

3-3 Ferrule, Compression Screw, and Union Assembly (Assembled).. 573-4 Waters 2695D Separations Module Tubing Bundles ..................... 583-5 Waters Transfer Module Rear Panel Fluidic Tubing Bundles ......... 603-6 Connecting the Fluidic Lines to the Uni-Probe with a Check Valve

Assembly ....................................................................................... 643-7 Connecting the Fluidic Lines to the Uni-Probe with Integrated Return

Line ................................................................................................ 643-8 Connecting the Fluidic Lines to the Uni-Probe with Discreet Return

Line ................................................................................................ 65

4-1 Waters 2695D Separations Module Controlling the Alliance Dissolution System and a Waters 486 or 2487 Detector ............... 68

4-2 Millennium³² Software Controlling the Alliance Dissolution System and a Waters 486. 2487, 996 or 2996 PDA Detector .................... 69

4-3 Waters 2695D Separations Module Rear Panel SignalConnections................................................................................... 70

4-4 2695D Separations Module Configuration Screen ........................ 714-5 Dissolution System Configuration Screen ..................................... 724-6 Pill Drop Options Dialog Box ......................................................... 744-7 Pill Drop Options Dialog Box with E-Probe Selected ..................... 754-8 Non-Millennium³² Data System Control of the Detector................. 774-9 Millennium³² Control of the Waters 474 or Other Detector Using the

busSAT/IN Module ......................................................................... 784-10 Waters Transfer Module Rear Panel Electrical Connections ......... 79

5-1 Dissolution System 2595D Main Screen ....................................... 835-2 Uni-Probe Wash Station Set Up to Prime Transfer Module ........... 855-3 Direct Functions Menu Screen ...................................................... 865-4 Set Up Transfer Module Dialog Box ............................................... 875-5 Create New Method Dialog Box..................................................... 905-6 Dissolution Method Name Dialog Box ........................................... 905-7 Dissolution Method Parametric View Screen................................. 915-8 Sample Timing Dialog Box ............................................................ 935-9 Separations Conditions Dialog Box ............................................... 95

List of Figures 15

5-10 Miscellaneous Options Dialog Box ................................................ 965-11 Dissolution Method Document Dialog Box .................................... 995-12 Dissolution Method Functional View Screen ............................... 1005-13 Dissolution Method Injection View Screen................................... 1005-14 Dissolution Method Loading View Screen ................................... 1015-15 Auto Standards Dialog Box.......................................................... 1025-16 Dissolution Method Parametric View with Pooling Enabled......... 1045-17 Dissolution Method Functional View with Pooling Enabled.......... 1045-18 Making a Sample Set from a Dissolution Method........................ 1055-19 Naming the Sample Set............................................................... 106

6-1 Run Samples Screen................................................................... 1086-2 Single-Bath Requirements Screen .............................................. 1096-3 Dual Bath Setup Screen .............................................................. 1116-4 Dual Bath Requirements Screen ................................................. 1126-5 First Drop Dosage Forms Prompt for Dual-Bath System............. 1136-6 Second Drop Dosage Forms Prompt for Dual-Bath System........ 1146-7 Vial Scanning Progress Bar......................................................... 1156-8 Vial Scanning Report Display ...................................................... 1166-9 Example of a Dissolution Test Report.......................................... 1186-10 Status Page for Alliance Dissolution System (Generic Bath)....... 1196-11 Status Page for Alliance Dissolution System

(Hanson SR8-Plus)...................................................................... 1216-12 Prompt to Continue HPLC Processing of Transferred Samples .. 1246-13 Status Page Layout Dialog Box ................................................... 125

7-1 Waters Transfer Module Syringe Assembly ................................. 1297-2 Removing Transfer Module Shoulder Screw................................ 1307-3 Removing Transfer Module Syringe Housing............................... 1317-4 Waters Transfer Module Rear Panel ............................................ 1327-5 Replacing the Filter on the Uni-Probe.......................................... 1337-6 Washing the Dissolution System Using the Uni-Probe Wash

Station.......................................................................................... 134

16 List of Figures

8-1 Diagnostics Screen...................................................................... 1448-2 Dissolution Diagnostics Screen ................................................... 145

List of Figures 17

18 List of Tables

1-1 Transfer Module Valves ................................................................. 32

2-1 Installation Site Requirements ...................................................... 422-2 Waters Transfer Module CPU Function LED Status ................. 51

3-1 Color Codes for Alliance Dissolution System FluidicConnections .................................................................................. 59

3-2 Waters Transfer Module Fluidic Connections ........................... 61

5-1 Alliance Dissolution System Devices Power Switch Locations ..... 825-2 Parametric View Screen Fields................................................ 915-3 Sample Timing Parameters ..................................................... 945-4 Separations Conditions Dialog Box Parameters ...................... 955-5 Miscellaneous Options Dialog Box Parameters ....................... 97

6-1 Method Icons .............................................................................. 1086-2 Dissolution Dispenser and Transfer Module Active States ..... 122

7-1 Routine Maintenance Procedures for the Waters Alliance Dissolution System ........................................................................................ 128

8-1 Dissolution System Error Messages ........................................... 1368-2 General Equipment Troubleshooting...................................... 149

A-1 Alliance Dissolution System Operational Specifications ............. 151

B-1 Waters Alliance Dissolution System Spare Parts List ................. 152

List of Tables

Preface

The Waters Alliance Dissolution System Operator’s Guide describes the procedures for unpacking, installing, operating, maintaining, and troubleshooting the Waters 2695D Separations Module and the Waters Transfer Module. The separations module and the transfer module, together with either one or two dissolution baths and a detector (Waters 486, 2487, 474, or 996/2996 PDA detectors are recommended), make up the Waters Alliance Dissolution System. This guide also describes instrument specifications, spare parts, and dissolution solvent considerations.

Use this guide with the Waters 2695 Separations Module Operator’s Guide, the operator’s guide for the dissolution system detector, and, if you are using Hanson SR8-Plus Dissolution Test Stations, the Hanson SR8-Plus Operational Manual (Hanson part number 73-100-800).

Organization

This guide contains the following:

Chapter 1 summarizes the features of the dissolution system and describes the theory and principles of operation.

Chapter 2 describes how to unpack and install the dissolution system and make power connections.

Chapter 3 describes how to make the fluidic connections between components of the dissolution system.

Chapter 4 describes how to connect the devices in the system to one or two baths, to a detector, and to other instruments and/or data systems.

Chapter 5 describes how to set up each component of the Waters dissolution system and develop a dissolution method.

Chapter 6 describes how to perform a dissolution test using the Alliance Dissolution System.

Chapter 7 describes how to clean and replace various parts of the dissolution system.

Chapter 8 describes error messages and diagnostics unique to the dissolution system.

Appendix A lists operational specifications for the Alliance Dissolution System.

Appendix B lists recommended and optional spare parts for the Alliance Dissolution System.

Appendix C provides information about using solvents with the Alliance Dissolution System.

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Related Documentation

Waters Licenses, Warranties, and Support: Provides software license and warranty information, describes training and extended support, and tells how Waters handles shipments, damages, claims, and returns.

Documentation on the Web

Related product information and documentation can be found on the World Wide Web. Our address is http://www.waters.com.

Online Documentation

Online documentation includes the following:

Millennium32 Help: Describes all Millennium32 windows, menus, menu selections, and dialog boxes for the base software and all the software options. Also includes reference information and procedures for performing all tasks required to use the Millennium32 software. Included as part of the Millennium32 software.

Millennium32 Read Me File: Describes product features and enhancements, helpful tips, installation and/or configuration considerations, and changes since the previous Millennium software version.

Millennium32 LIMS Help: Describes how to use the Millennium32 LIMS Interface to export results and import worklists.

Millennium32 Toolkit Professional Help: Describes how to use the common-object- model, message-based protocol to communicate with the Millennium32 software from a third-party application.

Millennium32 WebServer Help: Describes how to use the Millennium32 WebServer application.

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http://www.waters.com

Printed Documentation

Printed documentation that comprises the base product includes the following:

Millennium32 Read Me First: Describes the Millennium32 software documentation using a flowchart as a reading path.

Millennium32 Software Getting Started Guide: Provides an introduction to the Millennium32 software. Describes the basics of how to use Millennium32 software to acquire data, develop a processing method, review results, and print a report. Also covers basic information for managing projects and configuring systems.

Millennium32 Software Data Acquisition and Processing Theory Guide: Provides theories pertaining to data acquisition, peak detection and integration, and quantitation of sample components.

Millennium32 System Installation and Configuration Guide: Describes Millennium32 software installation, including the stand-alone workstation, PowerStation™ configuration, and client/server system. Discusses how to configure the computer and chromatographic instruments as part of the Millennium32 System. Also covers the installation, configuration, and use of acquisition servers such as the LAC/E32 module, the busLAC/E™ card, and interface cards used to communicate with serial instruments.

Millennium32 System Upgrade and Configuration Guide: Describes how to add hardware and upgrade the Millennium32 software using an import-and-export upgrade method.

Millennium32 Software Release Notes: Contains last-minute information about the product. Also provides supplementary information about specific Millennium32 software releases.

Printed Documentation for Options

Printed documentation that supports software options includes the following:

Millennium32 System Suitability Quick Reference Guide: Describes the basics of the Millennium32 System Suitability software application and describes the equations used by the System Suitability software.

Millennium32 PDA Software Getting Started Guide: Describes the basics of how to use the Millennium32 PDA option software to develop a PDA processing method and to review PDA results.

Millennium32 GPC Software Getting Started Guide: Describes how to use the Millennium32 GPC software option to develop a GPC processing method and to review GPC results.

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Millennium32 GPCV Software Getting Started Guide: Describes how to use the Millennium32 GPCV software option to develop a GPCV processing method and to review GPCV results.

Millennium32 ZQ Mass Detector Software Getting Started Guide: Describes installation, configuration, calibration, and tuning methods, as well as how to operate the ZQ Mass Detector with the Millennium32 software.

Millennium32 Chromatographic Pattern Matching Software Getting Started Guide: Describes how to use the Chromatographic Pattern Matching software option to develop a pattern matching processing method and to review pattern match results.

Millennium32 Dissolution System Software Quick Start Guide: Describes how to operate the Alliance® Dissolution System using Millennium32 software.

Waters Integrity System Getting Started Guide: Describes the features of the Waters Integrity® System and provides step-by-step tutorials that guide a user through the use of the Millennium32 Mass Spectrometry (MS) software option.

Millennium32 Toolkit Programmer’s Reference Guide: Describes how to use the common-object-model, message-based protocol to communicate with the Millennium32 software from a third-party application.

Millennium32 Client/Server System Administrator’s Guide: Describes how to administer Millennium32 software client/server tasks in a client/server system.

Millennium32 WebServer Installation and Configuration Guide: Describes how to install and configure the Millennium32 WebServer application.

Documentation Conventions

The following conventions may be used in this guide:

Convention Usage

Bold Bold indicates user action such as keys to press, menu selections, and commands. For example, “Click Next to go to the next page.”

Italic Italic indicates information that you supply such as variables. It also indicates emphasis and document titles. For example, “Replace file_name with the actual name of your file.”

Courier Courier indicates examples of source code and system output. For example, “The SVRMGR> prompt appears.”

Courier Bold Courier bold indicates characters that you type or keys you press in examples of source code. For example, “At the LSNRCTL> prompt, enter set password oracle to access Oracle.”

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Notes

Notes call out information that is helpful to the operator. For example:

Note: Record your result before you proceed to the next step.

Attentions

Attentions provide information about preventing possible damage to the system or equipment. For example:

Cautions

Cautions provide information essential to the safety of the operator. For example:

Keys The word key refers to a computer key on the keypad or keyboard. Screen keys refer to the keys on the instrument located immedi-ately below the screen. For example, “The A/B screen key on the 2414 Detector displays the selected channel.”

… Three periods indicate that more of the same type of item can optionally follow. For example, “You can store filename1, filename2, … in each folder.”

> A right arrow between menu options indicates you should choose each option in sequence. For example, “Select File > Exit” means you should select File from the menu bar, then select Exit from the File menu.

STOPAttention: To avoid damaging the detector flow cell, do not touch the flow cell window.

Caution: To avoid possible burns, turn off the lamp at least 30 minutes before removing it for replacement or adjustment.

Caution: To avoid possible electrical shock and injury, always turn off the detector and unplug the power cord before performing maintenance procedures.

Caution: To avoid chemical or electrical hazards, always observe safe laboratory practices when operating the system.

Convention Usage

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1
Chapter 1Dissolution System Theory of Operation
Note: To operate the Alliance Dissolution System, you must be familiar with the operation of the Waters 2695 Separations Module. See the Waters 2695 Separations Module Operator’s Guide for operating information.

Refer to Appendix A, Dissolution System Specifications, for system specifications. Refer to Appendix C, Solvent Considerations for a Dissolution System, for information about using solvents in a dissolution system.

If you use the Waters Alliance Dissolution System with the Millennium ³² Dissolution option software, refer to the Millennium³² Dissolution System Software Quick Start Guide and the Dissolution Overview topic in the Millennium³² Help for more information.

1.1 Dissolution Testing Overview

Dissolution testing ensures that pharmaceutical dosage forms dissolve under conditions designed to mimic human ingestion.

A typical dissolution bath apparatus contains either six or eight vessels. A single dosage unit is placed in each vessel and, at the end of a specified time, aliquots from the vessels are analyzed to determine the amount of the active ingredient that has dissolved. When this procedure is performed for only one time point, it is called single-point testing. Testing done at more than one time point is called multi-point testing.

STOPAttention: To maintain the integrity of the sample transfer mechanism, do not attempt to use an eight-needle Waters 2695D Separations Module as a six-needle system, or vice versa. The Waters Transfer Module is configured at manufacture for either six or eight syringes and must be installed with a corresponding six-or eight-needle Dissolution Dispenser within the 2695D Separations Module; otherwise, the warranty is voided.

Dissolution Testing Overview 24

1

1.2 Alliance Dissolution System Description

Overview

The Waters Alliance Dissolution System consists of:

• The Waters 2695D Separations Module, with a six- or eight-needle Dissolution Dispenser

• The Waters Transfer Module, with six or eight syringes

• One or two dissolution test baths (Hanson SR8-Plus™ or other manufacturer’s baths)

• Six or eight Uni-Probes™ (universal sampling probes), one for each dissolution vessel to be sampled

• A Waters 486, 2487, 474, or 996/2996 detector, or a non-Waters detector

• Millennium32 Dissolution Software Option, version 3.2 or higher.

The Waters 2695D Separations Module is a Waters 2695 XE Separations Module outfitted with a six- or eight-needle Dissolution Dispenser and dissolution software.

The Waters Transfer Module removes sample aliquots from the dissolution vessels and transfers them to empty vials loaded in the carousels of the 2695D Separations Module.

Note: The Alliance Dissolution System requires pre-slit septa for the sample vials used in the 2695D Separations Module and opaque sample vial caps for vial scanning.

The Waters Alliance Dissolution System can operate as a single-bath or dual-bath system. For more information, see, Chapter 4, Configuring Components, and Chapter 5, Setting Up the Dissolution System.

Although the dissolution system is optimized for use with one or two Hanson SR8-Plus dissolution baths, it can transfer samples from most commercially available dissolution baths using Uni-Probes (fixed-position universal sampling probes).

Figure 1-1 shows the required equipment layout for a dual-bath Alliance Dissolution System. For a single-bath system, the bath is positioned to the right of the Transfer Module.

During a dissolution test, aliquots of dissolution media (into which dosage forms have been placed and dissolved) are drawn at timed intervals from each dissolution vessel by the Transfer Module syringes and delivered to vials in the carousels of the 2695D Separations Module.

After the samples are delivered to the vials, the 2695D Separations Module injects the samples into the HPLC fluidic path by one of two methods, depending on the system configuration:

25 Dissolution System Theory of Operation

1

• Using the 2695D Separations Module as the system controller

• Using the Millennium³² Dissolution software option to control the system according to user-defined separation methods. For more information, refer to the Dissolution Overview topic in the Millennium³² Help.

The Alliance Dissolution System allows you to collect and process samples concurrently or to collect all samples and then perform HPLC analysis at a later time.

Wetted Surfaces

The wetted surfaces of the dissolution system (the Waters Transfer Module, the Waters 2695D Separations Module Dissolution Dispenser, and the Uni-Probes) are made of:

• Stainless steel

• PTFE

• PEEK™

• PVDF (polyvinylidene fluoride)

• Silicone

• Polycarbonate

• EPDM (ethylene propylene diene monomer)

Recommended Layout

Figure 1-1 shows the recommended bench layout for a dual-bath Alliance Dissolution System. If you have only one bath, Waters recommends that you locate it to the right of the Transfer Module.

Alliance Dissolution System Description 26

1

Figure 1-1 Waters Alliance Dissolution System (Dual-Bath), Recommended Layout

1.2.1 Waters 2695D Separations ModuleThe Waters 2695D Separations Module (Figure 1-2) includes the integrated PerformancePLUS™ vacuum degasser for chromatography, a column heater, optional column switching valve, a sample heater/cooler, and an integral plunger seal wash. The 2695D Separations Module also has a Dissolution Dispenser assembly (with six or eight needles) with associated inlet and outlet tubing (Figure 1-3).

In the Alliance Dissolution System, the 2695D Separations Module operates either as the system controller (stand alone mode) or under the control of the Millennium³² software.

Operator Interface

You can control the Alliance Dissolution System using either of the following interfaces:

• The 2695D Separations Module front panel keypad to program the 2695D Separations Module, the Waters Transfer Module, and the Hanson SR8-Plus test bath(s).

TP01551

Bath B (optional)

Bath A

Solvent Bottle Tray

ColumnHeater

2487Detector

2695DSeparations

Module

TransferModule


1

• The Millennium³² Dissolution software option. For more information on the Millennium³² Dissolution software option, see the Millennium³² Help or the Millennium³² Dissolution System Software Quick Start Guide.

Figure 1-2 Waters 2695D Separations Module with Column Heater

Dissolution Methods

You can create, change, and save dissolution methods (see Section 5.3.1, Developing a New Dissolution Method) using either the 2695D Separations Module for stand-alone operation or the Millennium³² Dissolution software option for remote control (see the Millennium³² Software Getting Started Guide or the Millennium³² Dissolution System Software Quick Start Guide).

You can also import and export dissolution methods as follows:

• For dissolution methods programmed on a 2695D Separations Module, you can use a 3.5-inch diskette to transfer methods to another 2695D Separations Module.

• When the Alliance Dissolution System is under control of the Millennium³² software, you can use the Millennium³² Dissolution software option to import or export dissolution methods with other Millennium³²-controlled dissolution systems.

TP01354

Column

3.5-inch Floppy Disk

Drive

Solvent Bottle Tray

User Interface

TP01354

Heater


1

Note: You can also use the 2695D Separations Module to create, process, analyze, and report non-dissolution sample set methods.

Dissolution Dispenser

The Dissolution Dispenser (Figure 1-3) is a subassembly of the 2695 Separations Module that allows six or eight sample aliquots from a dissolution bath to be delivered at one time to (six or eight) vials in the 2695D Separations Module sample management system. Each of the six or eight needles in the Dissolution Dispenser is connected to one of the six or eight syringes in the Waters Transfer Module through the Transfer Module valves (see Section 3.2.2, Connecting the 2695D Separations Module and the Transfer Module ).

Figure 1-3 Dissolution Dispenser

STOPAttention: To maintain the integrity of the sample transfer mechanism, do not attempt to use an eight-needle Waters 2695D Separations Module as a six-needle system or vice versa.

STOPAttention: To avoid damaging the 2695D Separations Module Dissolution Dispenser, use only pre-slit septa on the vials (see Appendix B, Spare Parts), and do not use low-volume inserts. Use only opaque vial caps to ensure that vial scanning operates properly.

TP01547

Interior View of 2695D Dissolution Dispenser

Assembly (eight-needle configuration)


1

If the 2695D Separations Module has a six-needle Dissolution Dispenser, the system requires a six-syringe Transfer Module; if the 2695D Separations Module has an eight-needle Dissolution Dispenser, the system requires the eight-syringe Transfer Module. You cannot use or adapt the Dissolution Dispenser to dispense a number of samples different from the number for which it is configured.

In the Dissolution Dispenser, six or eight individually mounted needle/seal bodies are arranged in an arc to match the vial spacing in the 2695D Separations Module carousel. Each needle contains two seals, located above and below a needle side port (when in the “up” position). A waste/recirculation tube exits from between the seals, and is directed either to waste or returned to the dissolution vessels. For the six-needle configuration of the 2695D Separations Module, the outer two needle positions are empty (Figure 1-4). The fluidic tubes connected to the needles are color-coded and numbered to facilitate making connections between the Waters 2695D Separations Module, the Waters Transfer Module, and the dissolution bath.

Only a qualified Waters service representative can replace the needles in the Dissolution Dispenser.

Figure 1-4 Dissolution Dispenser Needle Location and Fluidic Tubing Color-Code Diagram

The up or down motion of the needles corresponds to the function of the Dissolution Dispenser. Each needle is connected to:

• A tube from the Transfer Module for dispensing dissolution samples into vials.

• Another tube for removing the dispensed sample to waste or for recirculation of media.

This tubing exits in a bundle through a hole in the 2695D Separations Module rear panel.

The dissolution software in the Waters 2695D Separations Module allows movement of the carousel carrier only when the Dissolution Dispenser is in the home (up) position.

1

2

34

56

1

2

3

45

678

Six-Needle Configuration Eight-Needle Configuration

BlueGreen

Yellow

White

Red

Black

PurpleClear

BlueGreen

Yellow

White

Red

Black


1

Column Heater

The Waters 2695D Separations Module column heater allows you to maintain the column at temperatures between 20 °C (5 °C above ambient) and 60 °C. You can program an alarm to notify you if the temperature varies outside the specified range.

Column Switching

Optional column switching enables the system to switch column flow to one of several columns. This will allow you to run two separate methods sequentially. The column-selection valve is usually mounted in the Column Heater assembly housing and is either factory installed, or installed as an add-on option at a later time. The 2695D Separations Module software detects the presence and type of column selection valve at power on. You can specify column selection using the front panel, through the separations method or a part of the function of the sample set. Refer to the Waters 2695 Separations Module Operator’s Guide for additional information.

PerformancePLUS Vacuum Degasser

The Waters 2695D features the intergrated PerformancePLUS Vacuum Degasser. The design of this internal degasser combines a unique, variable-speed, continuously operating vacuum pump with innovative, high efficiency, low internal volume degasser chambers. This technology dramatically shortens instrument priming and equilibration times, allowing the system to become operational faster from an idle state or following a solvent change. Electronic control strategies are rugged, providing reliable long-term performance needed for continuous operation.

The degasser’s new Zero Hysteresis-Constant Run stepping motor-driven vacuum pump has been specifically designed and developed for membrane degassing of HPLC mobile phases. The continuously running pump cycles between high speeds, to provide rapid vacuum pull-down, while the low speed sustains a consistent vacuum level. This approach enables rapid vacuum equilibration for faster eluent equilibration. The continuous operating mode improves chromatographic performance for many high-sensitivity applications by eliminating the detector baseline drift or cycle that may be caused by pump hysteresis in discontinuous operating modes.

The PerformancePLUS Vacuum Degasser chambers achieve degassing efficiencies comparable to large-volume chambers, but with a fraction of the volume. Reduced from <11 mL to <500 uL, the degasser’s low-volume chambers substantially reduce prime effort, speed up solvent changeover, and increase reliability.

1.2.2 Waters Transfer ModuleThe Waters Transfer Module (Figure 1-5) automates the transfer of sample aliquots from the dissolution bath vessels to the Dissolution Dispenser in the Waters 2695D Separations


1

Module. The Waters Transfer Module has either six or eight syringes (depending on the configuration of the 2695D Separations Module).

The Transfer Module syringes draw samples from the dissolution vessels (at intervals programmed from the 2695D Separations Module front panel or through the Millennium³² Dissolution software) into the Dissolution Dispenser, then to vials in the 2695D Separations Module carousels. The Waters Transfer Module has no display or keypad, but it does have a Power On/Off indicator on the front panel (Figure 1-5).

Figure 1-5 Waters Transfer Module (Eight-Syringe Model)

The 2695D Separations Module then injects the samples onto the column as specified by user-defined separation methods or Millennium³² software instrument methods.

Four 2-way valves (A, B, C, and D) in the Waters Transfer Module open and close according to parameters specified in the dissolution method or Millennium³² sample set. The functions of the valves are indicated in Table 1-1.

Table 1-1 Transfer Module Valves

Valve Function

A Draws from/backflushes to Bath A vessels

B Draws from/backflushes to Bath B vessels

��

��

On/Off Switch

Syringe Assembly(eight-syringe

model)

Power On/Off LED


1

Once you connect the column heater to the 2695D Separations Module and make the necessary fluidic connections, you can place the detector on top of the Waters Transfer Module (see Figure 1-1).

Prime the Waters Transfer Module before each run and wash the syringes after each run. For information on priming and washing the Waters Transfer Module, seeChapter 5, Setting Up the Dissolution System.

Backflushing of the filters in the Uni-Probes and rinsing of the fluidic tubing occurs automatically after each sample is collected.

1.2.3 DetectorThe Alliance Dissolution System can operate with a Waters 486, 2487, 474, or 996/2996 PDA detector. In stand-alone mode, the 2695D Separations Module can control the Waters 486 or 2487 detector using the IEEE-488 interface. The 474 must be connected to a busSAT/IN™ module to communicate with a data system, and the 996/2996 PDA detector must be controlled by the Millennium³² software. The Alliance Dissolution System also supports non-Waters detectors using the busSAT/IN module.

When the detector is controlled by the 2695D Separations Module or a non-Millennium³² data system, you must connect the inject start output on the 2695D Separations Module rear panel to the detector (see the applicable detector operator’s guide) to signal the start of an LC injection.

You can control both the 2695D Separations Module and the detector using the Millennium³² software through a series of IEEE-488 connections. For additional information, see Chapter 4, Configuring Components, and the Waters 2695 Separations Module Operator’s Guide.

1.2.4 Dissolution Test Station (Bath)

C Draws from wash or media replace reservoir

D Dispenses to 2695D Separations Module (when Dissolution Dispenser is down) to waste or back to vessel

STOPAttention: For the Alliance Dissolution System to function properly as a dual-bath system, both baths must be either six-vessel or eight-vessel.

Table 1-1 Transfer Module Valves (Continued)

Valve Function


1

Note: If you use Hanson SR8-Plus dissolution test stations, become familiar with the procedures in the Hanson SR8-Plus Operational Manual. Hanson SR8-Plus calibration procedures are validated by Hanson Research, Inc. If you encounter problems with the Hanson SR8-Plus, contact Hanson Research, Inc.

The 2695D Separations Module controls and monitors one or two Hanson SR8-Plus Dissolution Test Stations (baths). However, the 2695D Separations Module can also be used with most commercially available dissolution test baths in either single or dual-bath operation.

Depending on the configuration, the Waters Transfer Module (Figure 1-5) draws six or eight dissolution samples at a time from each six- or eight-vessel dissolution bath through a Uni-Probe assembly (Figure 1-8).

1.2.5 Uni-Probe AssemblyThe Uni-Probe assembly (Figure 1-8) is a fixed-position universal sampling probe with sample and return tubes, with or without check valves, and a probe adjustment knob. Each Uni-Probe assembly has a fluidic connection to the Waters Transfer Module.

When a Waters Transfer Module syringe draws sample from a dissolution vessel, the check valve in the Uni-Probe allows the liquid to travel up through the sample tube through Valve A (or B if using two baths) and into the Waters Transfer Module syringes. When pressure is applied by the Transfer Module syringes to backflush the filters, the liquid travels back into the dissolution vessel through the return tube (Figure 1-8).

When Valve D is opened, the sample is dispensed to the sample vials according to the selected dissolution method.

Note: Media recirculation applies only to single-bath systems.

STOPAttention: For optimal system performance, use only filters with bidirectional flow capability and a nominal pore size of not less than 1.0 µm (such as the Gelman #4523 Glass Fiber Acrodisk® 1 µm × 25 mm filter). See Appendix B, Spare Parts, for part number information.

STOPAttention: To prevent changes in volume that may affect test results, use only the tubing bundles provided with the Alliance Dissolution System. Waters does not guarantee accurate test results when other tubing is used.

STOPAttention: To avoid damage to the Uni-Probe assembly or the Waters Transfer Module, do not use more than 10% organic in the dissolution vessel media, the replacement media, or the wash solvent.


1

Note: For non-SR8-Plus baths, the Waters Transfer Module can collect and transfer samples from the dissolution vessels to the 2695D Separations Module through Uni-Probes and fluidic connections.

Figure 1-6 Uni-Probe with Check Valve Assembly

Figure 1-7 Uni-Probe (no check valve) Assembly with Integrated Recirculation Line Port

Filter

Check Valve Assembly

Tube HeightAdjustment Knob

Media RecirculationTube

Return(Backflush)

Tube

Sample Tube

Media Level

To Transfer Module

Dissolution VesselCover

Tube HeightAdjustment

Knob

Filter

Media Level

Dissolution Cover

To Transfer Module

Return(Backflush)

Probe

Sample Probe

Integrated Recirculation Line

Recirculation LineConfiguration A

Vessel


1

Figure 1-8 Uni-Probe (no check valve) Assembly and Discrete Recirculation Line

1.2.6 Electric Sampling ProbesThe 2695D Separations Module supports Hanson SR-8 Plus dissolution baths equipped with optional electric sampling probes. The 2695D Separations Module can be configured to electronically synchronize to Hanson SR-8 Plus dissolution baths equipped with optional electric sampling probes.

When configured, the 2695D Separations Module is synchronized using an RS-232 handshake with the Transfer Module. A signal is communicated to the electric probes’ controller to start their task. Once the task is completed, the sampling controller sends a reply signal to the 2695D Separations Module that it has completed the task. Refer to Section 4.1.1, Configuring the 2695D Separations Module, for specific information regarding the 2695D Separations Module menu screen used for synchronization.

Optional Electric Sampling Probes for Hanson SR-8 Plus Baths

Two types of Electric probes are available for use with the Hanson SR-8 Plus dissolution bath. Dual-type probes (similar to Figure 1-8 except top-mounted) that have a return probe, and Single-type probes (Figure 1-9) which do not have a return probe. Single-


Knob

Filter

Media Level

To Transfer Module


Return(Backflush)

Probe

Sample Probe

Recirculation LineRecirculation LineConfiguration B

Dissolution CoverVessel


1

probe tubes have an internal dimension that is twice as large as the dual-probes (1/8-inch verses 1/16-inch.

Figure 1-9 Single-probe Configuration

1.3 Principles of Operation

After you develop your dissolution method using the 2695D (see Section 5.3.1, Developing a New Dissolution Method) or your sample set method using the Millennium32 software, you are ready to run a dissolution test.

If you use the 2695D Separations Module as the system controller, you select the dissolution method to download from the 2695D Separations Module to the Waters Transfer Module and to the Hanson SR8-Plus Dissolution Test Station(s), if installed (Figure 1-10 and Figure 1-11). If you use the Millennium³² software to control the dissolution system, refer to the Millennium³² Software Getting Started Guide and the Millennium³² Dissolution System Software Quick Start Guide for details on creating and using a dissolution-specific sample set method.

The 2695D Separations Module monitors the status of the Waters Transfer Module and the SR8-Plus bath(s) approximately once per second and displays this information on the 2695D Separations Module Status screen.

FilterTo Transfer Module

Sample Probe

Top Mounted E-Probe

Return Goes To Waste, or

Media Level

SR8PLUS

To The Recirculation Tubeon the Cover of the Vessel


1

If you use the SR8-Plus, during development of the dissolution method you enter paddle speed and temperature parameters for downloading to the Hanson SR8-Plus as part of the dissolution method.

If you do not use the SR8-Plus, the 2695D Separations Module has no control of paddle speed and temperature. You can, however, specify this information in the dissolution method to document the paddle speed and bath temperature.

Figure 1-10 Alliance Dissolution System Single-Bath Operation

With either an SR8-Plus or non-SR8-Plus bath, the sampling protocol (dissolution method) is entered at the Waters 2695D Separations Module or with the Millennium32 Dissolution software and the sampling intervals and volumes are downloaded to the Waters Transfer Module.

Bath A Media Replace or Wash

(Optional)

Waters 2695D Separations Module

Waters Transfer Module

Up

DownVialUp

Down

Home

Motor

Syringe

Valves

ABCD

Note: Volume of 1/32-in. ID tubing = 0.0126 mL/in.

Uni-Probe Assembly

(Home)

(Dispense)

38-in. (all four lines)[0.48 mL]

30-i

n.

[0.3

8 m

L]

[0.7 mL with filter]

[0.11 mL]

Unions

Waste

36-in.[0.45 mL]

60-

in.

[0.7

6 m

L]

36-in.[0.45 mL]

Union

60-i

n.

[0.7

6 m

L]

Recirculate to Vesselor Waste

Principles of Operation 38

1

According to the intervals and sample volumes specified in the dissolution method, the Transfer Module draws sample aliquots from the dissolution vessels and transfers them to the sample vials in the 2695D Separations Module.

After the samples have been transferred, the fluidic tubing between the Dissolution Dispenser and the sample vessels is backflushed with either fresh media (media replace) drawn through Valve C of the Transfer Module, or media from the dissolution vessels. You can also program a rinse (minimum 2.5 mL) of the fluidic lines from vessels to waste before each sample is taken.

Figure 1-11 Alliance Dissolution System Dual-Bath Operation

Note: Waters recommends a 7.5-mL rinse to minimize carryover.

Bath A Bath B

Media Replace or Wash

(Optional)

Waste



Up

DownVialUp

Down

Home

Motor

Syringe

Valves

ABCD


Uni-Probe Assembly

(Home)

(Dispense)

Unions


60-i

n.

[0.7

6 m

L]

6 0-i

n.

[0.7

6 m

L]

36

-in.

[0.4

5 m

L]

[0.11 mL]

36-in.[0.45 mL]

Union


60-

in.

[0.7

6 m

L]

60-

in.

[0.7

6 m

L]


1

When the 2695D Separations Module is not accepting samples from the Waters Transfer Module or not installed as part of the system configuration, it can perform sample analysis on previously acquired samples.

When the 2695D Separations Module is in the Controlled by Millennium³² mode, you can acquire, control, process, and analyze dissolution data and manage the results with the Millennium³² Dissolution software option. You can also use the Controlled by Millennium³² mode to run a non-dissolution sample set on the 2695D.

Principles of Operation 40

2

Chapter 2Installing the Dissolution System

This chapter describes how to unpack, install, and make power connections for the components of the Waters Alliance Dissolution System.

Information on making fluidic connections is covered in Chapter 3, Making Fluidic Connections. Information on configuring system components is covered inChapter 4, Configuring Components.

Figure 2-1 shows the major steps in installing the dissolution system.

Figure 2-1 Major Steps in Installing the Dissolution System

Start Installation Procedure

Installation Complete

Unpack and Inspect

Install Waters 2695D Separations Module

Install Column Heater

Install Bath A

Select Appropriate Site

Install Waters Transfer Module

Install Detector

Make Power Connections

Make Fluidic Connections (Chapter 3)

Install Bath B(if used)

Make Connections to Other Devices

(Chapter 4)

Make Signal Connections(Chapter 4)

41

2

Note: See the Waters 2695 Separations Module Operator’s Guide and the operator’s guide for the detector in use for information concerning access to these instruments.

Required Materials

• #2 Phillips screwdriver

• Flat-blade screwdriver

• 5/16-inch open-end wrench

• Waters Alliance Dissolution System Startup Kit

• Waters 2695 Separations Module Startup Kit

• Startup Kit for detector to be used

2.1 Site Selection and Power Requirements

Install the Waters Alliance Dissolution System in an area that meets the requirements listed in Table 2-1. See Figure 1-1 for the preferred installation setup for a dual-bath system. If you have a single bath, position it to the right of the 2695D Separations Module and Transfer Module.

To install the dissolution bath(s), see the installation instructions for the bath you are using.

Position the Waters Transfer Module front panel behind the hinge line of the 2695D column heater door to allow room to open and close the column heater door.

STOPAttention: There is no access to the 2695D Separations Module or the Waters Transfer Module from the top cover or the rear panel. The Waters Transfer Module contains no user-serviceable parts.

Table 2-1 Installation Site Requirements

Parameter Requirement

Operating temperature range 4 to 40 °C (39 to 104 °F)

Relative humidity 20 to 80%, noncondensing

Bench space requirement(for 2695D Separations Module with column heater, Waters Transfer Module, and Waters 2487 detector)

Width: 34.75 in. (88.265 cm)Depth: 25.0 in. (63.50 cm)Height: 22.5 in. (57.15 cm)Level to within ±2.0°

42 Installing the Dissolution System

2

Note: You can locate a Waters 486, 2487, 474, or 996/2996 detector on top of the Waters Transfer Module once you have made all power, signal, and fluidic connections. Make connections to the detector after you place it on top of the Transfer Module.

Fuse Requirements

The 2695D Separations Module does not have accessible external fuses. The power supply is designed with intergrated overvoltage protection circuitry that will shut down in case of an overload. If the 2695D Separations Module should shut itself down, the operator should switch the power off, wait several minutes, and switch the power on. If the 2695D Separations Module fails to restart, set the power switch to Off, disconnect the power connector from the main AC source, and contact your Waters Service representative.

To change a fuse in the:

Clearance At least 6 in. (15.24 cm) at the right side of Bath A and 2 in. (5.08 cm) in the rear for ventilation and wiring

Altitude Up to 6500 ft (2000 m)

Environmental conditions Installation Category IIPollution Degree 2

Power Grounded AC, 100 to 24 0Vac, 50 to 60 Hz

Electromagnetic fields No nearby source of electromagnetic noise, such as arcing relays or electric motors.

STOPAttention: To allow proper functioning of the solvent and waste management system and of the media recirculation and/or replacement system, if applicable, you must mount the dissolution system components on a level surface.

Caution: To avoid electrical shock, power off all instruments in the dissolution system and unplug all power cords before you replace any fuses.

Caution: To reduce the risk of fire hazard, always replace a fuse with the same type and rating.

Table 2-1 Installation Site Requirements (Continued)

Parameter Requirement

Site Selection and Power Requirements 43

2

• Waters Transfer Module, see Chapter 7, Maintaining the Dissolution System, for removal and replacement procedures

• Hanson SR8-Plus, see the Hanson SR8-Plus Operational Manual

• Non-Hanson SR8-Plus test bath, see the manufacturer’s documentation

• Detector, see the detector operator’s guide

2.2 Unpacking and Inspecting

The components of the Alliance Dissolution System are packed and shipped in three or more cartons that contain the following items:

• Waters 2695D Separations Module

• Waters Transfer Module

• Column heater

• Uni-Probe kit (six or eight) including wash station

• Waters 2487 detector, or other Waters detector (optional)

• Alliance Dissolution System Startup Kit, which includes the Waters Alliance Dissolution System Operator’s Guide

• Waters 2695 Separations Module Startup Kit, which includes the Waters 2695 Separations Module Operator’s Guide

• Certificate of structural validation/certificate of compliance

• Power cord

• Release notes

Unpacking and Inspecting

To unpack the Waters Alliance Dissolution System:

1. Unpack the contents of each shipping carton. As you unpack each carton, check that the contents match the packing list.

2. Check that the instrument serial numbers (found inside the syringe panel door of the Waters 2695D Separations Module and on the rear panel of the Waters Transfer Module) correspond to the numbers on the dissolution system validation certificate.

3. Check that the contents of each startup kit matches the startup kit list.

4. Save the shipping cartons for future transport or shipment.

5. If you detect any discrepancy in the contents of the order, contact Waters Technical Service at 800-252-4752, U.S. and Canadian customers only. Other customers, call your local Waters subsidiary or your local Waters Service Representative, or contact Waters corporate headquarters in Milford, Massachusetts (U.S.A.) for assistance.


2

If you detect any damage to the contents of the dissolution system, refer to the guide Waters Licenses, Warranties, and Support.

2.3 Making Electrical Power Connections

Connect the 2695D Separations Module and the Waters Transfer Module according to the instructions in this chapter. Connect the other components of the dissolution system according to the instructions in the individual instrument operator’s or installation guides.

Once you have made the power connections discussed in this section, go toChapter 3, Making Fluidic Connections, and Chapter 4, Configuring Components.

Figure 2-2 shows the rear panel connections for an Alliance Dissolution System that consists of a single Hanson SR8-Plus bath, a Waters 2487 detector, a Waters Transfer Module, a Waters 2695D Separations Module, and a column heater.

Figure 2-2 Waters Alliance Dissolution System Rear Panel Electrical Connections

STOPAttention: Do not power on the 2695D Separations Module until you have completed all fluidic and signal connections (see Chapter 3, Making Fluidic Connections, and Chapter 4, Configuring Components).

Hanson SR8-Plus


Power

Power

Power

Power

COMM

COMM

1 2 3

123

IEEE-488

RS-232B A

IEEE-488


(to Millennium³²)

Waters 2487 Detector

Column Heater

Making Electrical Power Connections 45

2

2.3.1 Connecting the Waters 2695D Separations ModuleThe 2695D Separations Module (Figure 2-3) accepts AC input voltages in two ranges:

• 85 to 132 Vac, 47 to 63 Hz

• 180 to 250 Vac, 47 to 63 Hz

To connect the power supply to the 2695D Separations Module:

1. Check that the Power On/Off switch (located on the upper left-hand side of the 2695D Separations Module) is in the Off (0) position.

2. Connect the power cord to the connector on the rear panel of the 2695D Separations Module (Figure 2-4).

3. Connect the other end of the power cord to a grounded AC power supply.

STOPAttention: The Waters Transfer Module is shipped with a 220 Vac rated power cord terminated with an 110 Vac plug. If you operate your dissolution system with 220 Vac, you must replace the 110 Vac plug with an appropriate rated termination connector, then connect the neutral line to the ground terminal. Waters recommends that only a qualified electrical technician perform this work.


2

Figure 2-3 Waters 2695D Separations Module Dimensions (Column Heater Attached)

2.3.2 Installing the Column Heater

The column heater is mounted on the right side panel of the 2695D Separations Module with three screws. A connector on the rear panel of the 2695D Separations Module separations module (see Figure 2-4) provides power and signal connections from the 2695D Separations Module to the column heater.

Required Materials

• Flat-blade screwdriver

STOPAttention: To avoid possible damage to components, power off the 2695D Separations Module before you connect or disconnect the column heater cable.

Caution: To avoid the risk of injury, do not remove the cover plate on the side of the 2695D Separations Module sample compartment.

TP01354

Column

SampleCompartment

23.0 in.(58.42 cm)

22.5 in.(57.2 cm)

3.5-inch Disk Drive

24.0 in.(60.1 cm)

Solvent Bottle Tray Heater


2

• Screws and retaining washers, three (from 2695 Separations Module Startup Kit)

• Column heater cable

To install the column heater (also refer to the Waters 2695 Separations Module Operator’s Guide, Section 2.6, Making Fluidic Connections):

1. Power off the 2695D Separations Module and unplug the instrument from the AC power source.

2. Install the three screws and retaining washers (from the 2695D Separations Module Startup Kit) on the right side panel.

3. Route the red outlet tubing through the slot located halfway up the front chassis of the Separations Module.

4. Mount the column heater on the right side panel, using the three screws and retaining washers installed in step 2.

5. Connect one end of the column heater cable to the rear of the column heater. Connect the other end of the cable to the connector on the rear panel of the 2695D Separations Module (Figure 2-4).

Figure 2-4 2695D Separations Module Rear Panel Electrical Connections

TP01546

I/O Connectors A and B

Column Heater Connector

Fluidic Connectionsto Transfer Module

Power Connector

B A

B ARS-232

Connectors

IEEE-488Connector


2

2.3.3 Connecting the Waters Transfer Module

To connect the Waters Transfer Module (Figure 2-5) to the 2695D Separations Module, connect an RS-232 serial cable from the 2695D Separations Module RS-232 B connector (see Figure 2-4) to the Waters Transfer Module at COMM 1.

Note: The RS-232 A connector at the 2695D Separations Module cannot be used to connect the Waters Transfer Module.

Communication (Comm) ports 1, 2, and 3 are designed to be used for specific instrumentation, as shown in Figure 2-2.

Desktop Power Supply Module

The Waters Transfer Module is shipped with a separate DC power supply. The Desktop Power Supply Module (Figure 2-6) allows you to connect the Waters Transfer Module to any 100 to 240 Vac power source when used with the proper connector. The input connector for the desktop power supply is located on the rear panel of the Transfer Module.

Connection Procedure

The Desktop Power Supply Module is in the Waters Alliance Dissolution System Startup Kit. To connect the Waters Transfer Module to an electrical power source:

1. Check that the power On/Off switch on the side of the Transfer Module is Off (0) (Figure 2-5).

2. Plug the Desktop Power Supply Module input jack into the receptacle on the rear panel of the Transfer Module (Figure 2-6).

3. Plug the Desktop Power Supply Module power connector into a grounded AC power source.

4. Do not apply power to the Waters Transfer Module until you have completed all fluidic and component connections (see Chapter 3, Making Fluidic Connections, and Chapter 4, Configuring Components).

Caution: Communication ports 1, 2, and 3 on the rear panel of the Waters Transfer Module (Figure 2-2) do not accept telephone-type modular connectors. Do not attempt to plug a modular telephone connector into any receptacle on the Transfer Module.

Caution: To avoid electrical shock or an electrical circuit failure, disconnect the desktop power supply module from the wall power unit before you disconnect it from the Waters Transfer Module.


2

Figure 2-5 Waters Transfer Module Dimensions

Figure 2-6 Waters Transfer Module Rear Panel and Desktop Power Supply Module

��

��

11.25 in.(28.58 cm)

19.25 in. (48.90 cm)

14.25 in.(36.20 cm)

FrontPanel

Power

LEDOn/Off

TP01557

Desktop Power Supply

Waters Transfer ModuleRear Panel

Desktop Power SupplyInput Jack Receptacle

CPU Function LED


2

Transfer Module Status Indicators

The Waters Transfer Module indicates the status of its communications with other equipment in the Alliance Dissolution System using the Power On/Off LED on the Transfer Module front panel (Figure 2-5) and the CPU Function LED on the rear panel (Figure 2-6 and Figure 2-7).

If power to the Transfer Module is On, the green front panel LED is illuminated. If power to the Transfer Module is Off, the green front panel LED is not illuminated.

Table 2-2 describes each condition of the CPU Function LED indicator on the rear panel of the Waters Transfer Module.

Note: After you connect the Waters Transfer Module to the Waters 2695D Separations Module, it may take up to 30 seconds for communication to be established.

Table 2-2 Waters Transfer Module CPU Function LED Status

Transfer Module CPU Function LED

StatusDescription

Steady or blinking green

Power is on and the Waters Transfer Module is communicating with 2695D Separations Module. The LED may blink during startup.

Off Power is switched off.

Red Malfunction, CPU fault (see Table 8-2).


2

Figure 2-7 Waters Transfer Module Rear Panel Electrical Connections

COMM

1 2 3

CP

U F

UN

CT

ION

AUXILIARYI/O

TP01545

3A TT FUSE

To 2695D

To Hanson

RS-232 B

SR8-Plus Bath A

For Future Use

Fuse

Desktop Power SupplyInput Jack


3

Chapter 3Making Fluidic Connections

STOPAttention: To prevent changes in volume that may affect system specifications, use the tubing supplied with your Alliance Dissolution System. Waters cannot guarantee accurate results if other tubing is used.

STOPAttention: To avoid damaging the 2695D Dissolution Dispenser, use only pre-slit vial septa (see Appendix B, Spare Parts), and do not use low-volume inserts. Use only opaque caps to ensure that vial scanning operates properly.

STOPAttention: For the Alliance Dissolution System to function as a dual-bath system, both baths must be either six-vessel or eight-vessel.


STOPAttention: For optimal system performance, use filters with bidirectional flow capability and a nominal pore size of not less than 1.0 µm (such as the Gelman #4523 Glass Fiber Acrodisk 1 µm x 25 mm filter, part number WAT200818).

Caution: To prevent injury, always observe safe laboratory practices when handling solvents, changing tubing, or operating the Alliance Dissolution System. Know the physical and chemical properties of the solvents you use. Refer to the Material Safety Data Sheets for the solvents you use.

53

3

3.1 Overview

Two kinds of tubing are used for fluidic connections in the Waters Alliance Dissolution System:

• Stainless steel – For connections between the column and the detector and between the 2695D Separations Module and the detector or column.

• PTFE – For connections between the 2695D Separations Module and the Waters Transfer Module, between the Transfer Module and the dissolution test bath(s), between the solvent supply and the 2695D Separations Module, and between any instrument and waste, wash, recirculation, or media replace.

For information on making fluidic connections using 1/16-inch OD stainless steel tubing, refer to the following:

• Waters 2695 Separations Module Operator’s Guide, Section 2.5, Making Fluidic Connections.

• Operator’s guide for the detector in your dissolution system

Dissolution Component Connections

The fluidic connections between the dissolution components of the Alliance Dissolution System are between:

• Uni-Probes (and their dissolution vessels) and the Waters Transfer Module

• Waters Transfer Module and media replace or wash, if applicable

• 2695D Dissolution Dispenser and a waste reservoir

• 2695D Separations Module and the Waters Transfer Module

Note: You can place the Waters 486, 2487, 474, or 996/2996 detector on top of the Waters Transfer Module after you make all system power, signal, and fluidic connections.

Chromatography Component Connections

To make the following fluidic connections between chromatographic components of an Alliance Dissolution System, refer to the Waters 2695 Separations Module Operator’s Guide, Section 2.5, Making Fluidic Connections, or other indicated operator’s guide:

• Between the solvent supply and the 2695D Separations Module

• Between the 2695D Separations Module spill tray (or condensation) and waste

• Between the 2695D Separations Module and the column

• Between the column and the detector

• Between the detector and a waste reservoir – see the applicable detector operator’s guide

54 Making Fluidic Connections

3

Fluidic Path Diagram

Note: In the Alliance Dissolution System, six or eight tubing lines per bundle exit from the rear of the Waters Transfer Module, one bundle for each valve in the Transfer Module.

Figure 3-1 shows a view of the fluidic connections between the Waters Transfer Module and a single bath, media replace or wash vessels, and the 2695D Separations Module. Tubing lengths and volumes are indicated. Figure 1-11 provides a similar view of a dual-bath installation.

Figure 3-1 Waters Alliance Dissolution System Single-Bath Installation

Bath A Media Replace or Wash

(Optional)

Recirculate to Vesselor Waste



Up

DownVialUp

Down

Home

Motor

Syringe

Valves

ABCD


Uni-Probe Assembly

(Home)

(Dispense)


30-i

n.

[0.3

8 m

L]


[0.11 mL]

Unions

Waste

36-in.[0.45 mL]

60-

in.

[0.7

6 m

L]

36-in.[0.45 mL]

Union

60-i

n.

[0.7

6 m

L]

Overview 55

3

3.2 Connecting the System Fluidics

3.2.1 Assembling Fluidic Connections

Note: Fluidic tubing connections to dissolution system components need to be only finger-tight; no special tools are required.

Required Materials

• Uni-Probe filters, six or eight for single bath, 12 or 16 for dual bath (in Waters Alliance Dissolution System Startup Kit)

• Tubing, six or eight lengths of 30-inch tubing for single-bath system; six or eight lengths of 60-inch tubing for dual-bath system (in Waters Alliance Dissolution System Startup Kit)

• Fittings, six or eight kits for single-bath system, 12 or 16 for dual-bath system (in Waters Alliance Dissolution System Startup Kit)

To assemble a union fitting for fluidic tubing connections:

1. Slide a compression screw and then a ferrule over one end of a length of Teflon® tubing as shown in Figure 3-2.

Note: Set the tubing end flush with the end of the ferrule.

2. Repeat step 1 for the other end of tubing.

STOPAttention: To prevent damage to the Waters 2695D Separations Module and to the Waters Transfer Module, be sure to use wash solutions that are miscible with the mobile phase and dissolution media you are using. Do not use organic solvents, except methanol (up to 10% organic only).

STOPAttention: To prevent changes in volume that may affect system specifications, use the tubing bundles provided with the Alliance Dissolution System. Waters does not guarantee accurate test results when other tubing is used.

STOPAttention: To prevent damage to the ferrules, do not overtighten the assembly fittings.


3

Figure 3-2 Ferrule, Compression Screw, and Union Assembly (Exploded View)

Figure 3-3 Ferrule, Compression Screw, and Union Assembly (Assembled)

3. Screw a compression screw into one end, then into the other end of the union, alternating until the ferrule ends meet in the middle of the union, as shown in Figure 3-3.

4. Finger-tighten the fittings.

3.2.2 Connecting the 2695D Separations Module and the Transfer Module

When you operate the Alliance Dissolution System as a single-bath system (see Figure 3-1):

• Valves A and D of the Transfer Module are used to transfer samples to the 2695D Separations Module.

• Valve C is used for wash or to replace media.

• Valve B remains closed and no tubing is connected.

TP01548

Tubing

Ferrule

Union

Ferrule Compression Screw

TP01549

Tubing

Ferrules

Union

Compression Screw

Connecting the System Fluidics 57

3

The tubing through which the fluid moves is provided by:

• Two bundles of tubing that extend from an opening in the rear panel of the 2695D Separations Module (Figure 3-4). Each bundle consists of either six or eight tubes, depending on the configuration of your 2695D Separations Module. The bundles are labeled:

– Dispenser Needle Body (Lower) – To be routed to waste or recirculated back to vessel (single-bath only)

– Dispenser Needle Body (Upper) – To be routed to Valve D of the Transfer Module

• Four bundles of tubing that extend from the four openings (labeled “Liquid Interface Connection”) in the rear panel of the Waters Transfer Module (see Figure 3-5).

Figure 3-4 Waters 2695D Separations Module Tubing Bundles

Connecting the 2695D Fluidics in a Single-Bath System

To make fluidic connections between the 2695D Separations Module and the Transfer Module for a single-bath system:

1. Connect the Dispenser Needle Body (Lower) bundle on the 2695D Separations Module as follows:

• If you want to recirculate media back to the dissolution vessel, use 60-inch tubing to connect each tube in the Dispenser Needle Body (Lower) bundle to a 1/4-in.-28 fitting adapter that fits in the Uni-Probe cover (see Section 3.2.4,

TP01546

Tubing Bundles Exiting from Rear

Panel of the 2695D


3

Connecting the Uni-Probes, the “Connecting the Recirculation Fluidic Lines” discussion).

• If you do not want to recirculate media back to the dissolution vessels, connect the 60-inch tubing set (all 6 or 8 lines) to a waste reservoir.

2. Locate the Valve D bundle on the rear of the Waters Transfer Module (see Figure 3-5).

3. Using the color codes provided in Table 3-1 and the labels on the tubing bundles, connect each tube from the Dispenser Needle Body (Upper) bundle on the 2695D Separations Module to the corresponding tube in the Valve D bundle from the Transfer Module.

For example, connect the tube labeled #1 Black from the Dispenser Needle Body (Upper) bundle on the 2695D Separations Module to the tube labeled #1 D (which has a black compression screw) in the Transfer Module Valve D bundle.

4. Ensure all connections are finger-tight.

Connecting the 2695D Fluidics in a Dual-Bath System

To make the fluidic connections between the 2695D Separations Module and the Waters Transfer Module in a dual-bath system (see Figure 1-11):

1. Connect all tubing from the Dispenser Needle Body (Lower) bundle on the 2695D Separations Module to the waste reservoir.

2. Locate the Valve D bundle on the rear of the Waters Transfer Module (see Figure 3-5).

3. Using the color codes provided in Table 3-1 and the labels on the tubing, connect each tube from the Dispenser Needle Body (Upper) bundle to the corresponding tube in the Valve D bundle on the Transfer Module.

Table 3-1 Color Codes for Alliance Dissolution System Fluidic Connections

Syringe Number Fitting Color

1 Black

2 Red

3 White

4 Yellow

5 Green

6 Blue

7a

a. Used only in an 8-needle system

Clear

8a Purple


3

For example, connect the tube labeled #1 Black from the Dispenser Needle Body (Upper) bundle on the 2695D Separations Module to the tube labeled #1 D (which has a black compression screw) in the Transfer Module Valve D bundle.

4. Ensure all connections are finger-tight.

Figure 3-5 Waters Transfer Module Rear Panel Fluidic Tubing Bundles

3.2.3 Connecting the Waters Transfer Module and the Dissolution Bath Vessels

Four tubing bundles labeled A, B, C, and D exit from the Waters Transfer Module rear panel, as shown in Figure 3-5. Each bundle consists of six or eight tubes.

• For a single-bath system, 30 inches of tubing are needed to connect each vessel in the bath to the corresponding valve tube from the Transfer Module.

• For a dual-bath system, 60 inches of tubing are needed to connect each vessel in the two baths to the corresponding valve tube from the Transfer Module.

• Another 60 inches of tubing are needed if you are recirculating media into the vessels (you can specify recirculation for single-bath systems only).

TP01544

COMM

1 2 3

CP

U F

UN

CT

ION

AUXILIARYI/O

3A TT FUSELIQUID

INTERFACECONNECTIONS

A B

C D Tubing Bundles A, B, C, and D

Electrical Connections

LIQUID INTERFACECONNECTIONS


3

• The 30-inch and 60-inch tubing lengths are shipped as part of the Waters Alliance Dissolution System Startup Kit.

The tubing from each bundle in the Waters Transfer Module is connected as shown in Table 3-2.

Connecting the Transfer Module to a Single Bath

Note: The Valve B bundle and its 60-inch tubing extensions are not used in a single-bath operation.

To connect the fluidic tubing from the Waters Transfer Module to the dissolution test bath in a single-bath system:

1. If you have not already done so, connect the tubing from the Waters Transfer Module Valve D bundle to the Dispenser Needle Body (Upper) bundle from the 2695D Separations Module using the color codes provided in Table 3-1.

2. Connect each tube from the Bath A vessels to the corresponding tube in the Waters Transfer Module Valve A bundle according to the color codes provided in Table 3-1 and the labels on the tubing.

STOPAttention: To prevent changes in volume that may affect test results, use only the tubing provided with the Alliance Dissolution System. Do not change the tubing lengths or diameters as shipped. Waters does not guarantee accurate test results when other tubing is used.

Table 3-2 Waters Transfer Module Fluidic Connections

Waters Transfer Module Valve Tubing

Connection

A Bath A vessels

B Bath B vessels (not used in a single-bath system)

C Media replace (if used) or washa

a. May contain HPLC-grade water or clean dissolution media. The automatic rinse that occurs before each sample is removed contains dissolution media with sample.

D Dispenser Needle Body (Upper) bundle from 2695D Separations Module


3

3. Connect each of the six or eight tubes from the Waters Transfer Module Valve C bundle to a 30-inch tubing extension, then to a media replace or wash vessel (which may be in Bath A).

The Bath A tubes may then be connected to Uni-Probes (see Section 3.2.4, Connecting the Uni-Probes).

Connecting the Transfer Module to a Dual Bath

To connect the fluidic tubing from the Waters Transfer Module to the dissolution test baths in a dual-bath system:

1. If you have not already done so, connect the tubing from the Waters Transfer Module Valve D bundle to the Dispenser Needle Body (Upper) bundle from the the 2695D Separations Module.

2. Connect each tube from Bath A to the corresponding tube in the Waters Transfer Module Valve A bundle according to the color codes provided in Table 3-1 and the labels on the tubing.

3. Connect each tube from Bath B to the corresponding tube in the Waters Transfer Module Valve B bundle according to the color codes provided in Table 3-1 and the labels on the tubing.

4. Connect all six or eight tubes from the Waters Transfer Module Valve C bundle to a media replace or wash vessel (which may be in Bath A or Bath B).

The Bath A and Bath B tubes may then be connected to Uni-Probes (see Section 3.2.4, Connecting the Uni-Probes).


3

3.2.4 Connecting the Uni-Probes

The Uni-Probe assembly (Figure 3-6) consists of:

• Sample and return probes with or without a check valve assembly

• Probe adjustment knob

• Vessel cover

• Media recirculation probe

• 1/4–28 recirculation fitting

For the various configurations of Uni-Probes provided by Waters, see Appendix B, Spare Parts.

Uni-Probes can be setup in various configurations to fit your dissolution system needs.

– Figure 3-6 shows the fluidic connection of the Uni-Probe assembly equipped with a check valve.

– Figure 3-7 and Figure 3-8 shows two fluidic connection configurations for Uni-Probes without a check valve assembly.

• Figure 3-7, Configuration A shows the fluidic connection setup for a Uni-Probe with an integrated media recirculation line connection.

• Figure 3-8, Configuration B shows the fluidic connection setup for an Uni-Probe and a discrete media recirculation line connection

STOPAttention: Before you install the Uni-Probes and before you operate the dissolution system for the first time, be sure to prime the fluidic lines with 15 mL of dissolution media.

STOPAttention: To prevent changes in volume that may affect test results, use the tubing provided with the Alliance Dissolution System. Waters does not guarantee accurate test results when other tubing is used.


STOPAttention: Before you connect the Uni-Probe to the Transfer Module fluidic lines, you must install a filter on the Uni-Probe.


3
Figure 3-6 Connecting the Fluidic Lines to the Uni-Probe with a Check Valve Assembly
Figure 3-7 Connecting the Fluidic Lines to the Uni-Probe with Integrated Return Line

Filter1/32-in. ID1/16-in. OD

3.25 in. length

Return Probe

Sample Probe

1/32-in. ID1/16-in OD

1/4-in.-28 fitting

Cover

Male Adapter

To Transfer Module

To Media Recirculation

Media Level

Check Valve Assembly

1/8-in. OD

1/16-in. OD

Probe Height Adjustment Knob


Knob

Filter

Media Level

Dissolution

Cover

To Transfer Module

Sample Probe

Integrated Recirculation Line

Recirculation LineConfiguration A

1/8-in. OD

1/16-in. OD

Return Probe

Vessel


3

Figure 3-8 Connecting the Fluidic Lines to the Uni-Probe with Discreet Return Line

Connecting the Transfer Module and the Uni-Probe Assembly

To connect the tubing from the Uni-Probes to Bath A (and Bath B, if used):

1. Assemble the compression screw and ferrules (Figure 3-2) from the Waters Transfer Module, valve bundle A (and valve bundle B when two baths are used). At the fluidic connection to the Transfer Module, screw first one compression screw, then the other, until the union is finger-tight.

2. Slip the stainless steel male adapter (on the Uni-Probe assembly) into the small length of tubing extending from the Valve A bundle.

Note: Using a small piece of fine sandpaper to grip the tubing avoids damaging or kinking during this procedure.

3. Insert the Uni-Probe assembly with filter and completed fluidic connection into the large hole in the vessel cover, then place the cover and Uni-Probe assembly on top of a dissolution bath vessel.

4. Adjust the depth of the probe in the vessel using the Probe Height Adjustment knob (see Figure 3-6).

Installing a Filter onto a Single- or Uni-Probe Assembly

STOPAttention: To minimize sample carryover, Waters recommends that you change the filter on each Probe assembly at the beginning of each dissolution test.


Knob

Filter

Media Level

Dissolution

Cover

To Transfer Module


Sample Probe

Recirculation Line

Recirculation LineConfiguration B

1/4-in.-28 fitting

1/32-in. ID1/16-in. OD

1/8-in. OD

1/16-in. OD

Return Probe

Vessel


3

Before connecting the fluidic lines from the Transfer Module to the Probe Assembly, install a filter in each Probe Assembly.

To install a filter:

1. Disconnect the Probe from its connection to the Transfer Module.

2. Remove the old filter, then install the new filter onto the Probe assembly, as shown in Figure 3-6 or Figure 3-7.

3. Reassemble the Probe to the Transfer Module.

Connecting the Recirculation Fluidic Lines

Note: The procedure in this section applies to single-bath Uni-probe systems only.

To recirculate media back to the dissolution vessel in a single-bath system:

1. Slip a 1/4–28 fitting and a reverse ferrule onto the end of the waste line.

2. Screw the fitting into the 1/4-28 port on the dissolution vessel cover (see Figure 3-6).

3. Push the waste tubing end through the ferrule, as shown in Figure 3-6.

4. Configure the 2695D Separations Module to recirculate media to vessels (see Section 4.1.1, Configuring the 2695D Separations Module, Figure 4-5.

For Single-bath Systems with Electric Probes

Attach the waste line to the stainless steel male fitting on the electric probe.

3.2.5 Connecting Electric ProbesThe Waters 2695D Separations Module supports the use of dissolution sampling probes (see Chapter 1, Figure 1-9) that are raised and lowered by means of electric motors. For additional information related to installation and fluidic connections, refer to the manufacturer’s information supplied with the electric probes.


STOPAttention: Do not immerse the recirculation tubing in liquid


4

Chapter 4Configuring Components

Depending on which configuration you select for your Alliance Dissolution System, you can use the RS-232 cable, the IEEE-488 cable, the busSAT/IN module, and the Analog I/Ocable to provide electrical signal connections among the system components.

You can set up the Waters Alliance Dissolution System in any one of the following ways:

• With the 2695D Separations Module as the system controller:

– The 2695D Separations Module controls the Waters Transfer Module, the Hanson SR8-Plus bath(s), and a Waters 486 or 2487 detector, with the Millennium³² data system or a non-Waters data system performing data collection (Figure 4-1).

– The 2695D Separations Module controls the Waters Transfer Module and the Hanson SR8-Plus bath(s) only, with the Millennium³² data system or a non-Waters data system controlling the detector and performing only data collection.

– The 2695D Separations Module controls only the Waters Transfer Module and can record limited information from a non-Hanson bath system. Data is collected separately by a Millennium³² or a non-Waters data system.

• With the Millennium³² software (with the dissolution software option installed) as the system controller:

– The Millennium³² software controls the 2695D Separations Module, the Waters Transfer Module, and the Hanson SR8-Plus bath(s) (Figure 4-2).

– The Millennium³² software controls the 2695D Separations Module and the Waters Transfer Module, using a third-party dissolution test bath.

– The Millennium³² software controls the 2695D Separations Module, the Waters Transfer Module, and the Hanson SR8-Plus bath(s), and a Waters 486, 2487, or 996/2996 PDA detector.

– The Millennium³² software controls the 2695D Separations Module, the Waters Transfer Module and the bath(s). Data from a Waters 474 detector is transmitted to the Millennium³² data system through the Waters busSAT/IN module

Refer to the Waters 2695 Separations Module Operator’s Guide, Section 2.7, Signal Connections, for information on the analog and digital signal connections you can make to the terminal strips, RS-232, and IEEE-488 connectors on the rear panel of the 2695D Separations Module.

This section provides information on configuring the 2695D Separations Module and configuring and connecting the other components of your dissolution system.

67

4

Figure 4-1 shows the signal connections in a Waters Alliance Dissolution System with the 2695D Separations Module controlling the Waters Transfer Module, two Hanson SR8-Plus baths, and the Waters 486 or 2487 detector, with the Millennium³² performing data collection.

Figure 4-2 shows the signal connections in a Waters Alliance Dissolution System with the Millennium³² software controlling the 2695D Separations Module, the Waters Transfer Module, the Waters 2487 detector, and two Hanson SR8-Plus baths.

Figure 4-1 Waters 2695D Separations Module Controlling the Alliance Dissolution System and a Waters 486 or 2487 Detector

Note: The RS-232 cable from the 2695D Separations Module to the Waters Transfer Module is a 9-pin to modular custom cable.

2695DSeparations

Module

Waters 486 or 2487 Detector


Hanson SR8-Plus (Bath A)

Hanson SR8-Plus (Bath B)

Optional Hanson Printer

Serial Printer (optional)

RS-232 Cable

RS-232 Cable

Inject Start

(supplied byHanson)

A*

B*

1*

1*

2*

1*

2*

3*

Signal

Note: The * indicates the number or letter of the RS-232

IEEE-488

Millennium³²Data System


3*

RS-232 Cable(supplied by

Hanson)

68 Configuring Components

4

Figure 4-2 Millennium³² Software Controlling the Alliance Dissolution System and a Waters 486. 2487, 996 or 2996 PDA Detector

For details on connecting the Waters 2487 Dual λ Absorbance Detector to the Millennium³² data system, see the Waters 2487 Dual λ Absorbance Detector Operator’s Guide.

For details on connecting the Waters 996/2996 PDA Detector, see the Waters 996 Photodiode Array Detector Operator’s Guide or the Waters 2996 Photodiode Array Detector Operator’s Guide.

4.1 Operating Configurations

In the Alliance Dissolution System, the 2695D Separations Module operates either as the system controller or under the control of the Millennium³² software.

When configured as the system controller, the 2695D Separations Module controls the Waters Transfer Module and one or two Hanson SR8-Plus dissolution test baths, and can

2695DSeparations

Module






Serial Printer (optional)

RS-232 Cable

RS-232 Cables

IEEE-488

(supplied byHanson)

A*

B*

1*

1*

2*

1*

2*

3*

Note: The * indicates the number or letter of the RS-232 port.

Waters 486, 2487, or

996/2996 PDA Detector


3*

Operating Configurations 69

4

also control the Waters 486 or 2487 detectors through the IEEE-488 connector or the signal ports shown in Figure 4-3.

Figure 4-3 Waters 2695D Separations Module Rear Panel Signal Connections

You can control the Alliance Dissolution System and the Waters 486, 2487, and 996/2996 PDA detectors from a Millennium³² data system through an IEEE-488 cable, or you can use the I/O connector on the rear panel of the 2695D Separations Module to input an inject start signal to the detector. You can monitor a Waters 474 detector using the Waters busSAT/IN module, with an inject start input from the 2695D Separations Module to the busSAT/IN module.

Some of the connections you make between components of your dissolution system depend on the type of components that you configure with the system. The following sections describe the types of connections available for most dissolution system configurations.

TP01357A

RS-232 Aux B Connector (to Waters

Transfer Module)

Event and I/O Signal Connections(see the Waters 2695 Separations Module

Operator’s Guide, Section 2.6,Signal Connections)

IEEE-488 Connector (to IEEE-488-Compatible Detector

and/or to busLAC/E modulefor Millennium³² control)


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4.1.1 Configuring the 2695D Separations ModuleBefore you can make signal connections between the components of your dissolution system, you need to configure the 2695D Separations Module.

Procedure

To configure the 2695D Separations Module:

1. From the 2695D Separations Module Main screen, press the Config screen key to display the Configuration screen (Figure 4-4).

Figure 4-4 2695D Separations Module Configuration Screen

2. From the system drop-down list, select the 2695D Separations Module operating configuration:

• System Controller – Specifies the 2695D Separations Module as the system controller.

• Controlled by Millennium32 – Specifies the Millennium³² data system as the system controller. Enter an IEEE-488 address that does not conflict with any other device controlled by the Millennium³² data system.

Note: When the Alliance Dissolution System is under the control of the Millennium³² software, you select the dissolution parameters, such as bath temperature and paddle speed, injection volume, and so on, when you create a dissolution sample set method. For more information, see the Millennium³² Dissolution System Software Quick Start Guide or the “Creating a Sample Set Method in Run Samples Using the Wizard” topic in the Millennium³² Help.


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• No Interaction – Specifies the 2695D as the system controller, with no interaction to the installed detector or the data system.

For information on how to set other configuration parameters in the 2695D Separations Module Configuration screen, see the Waters 2695 Separations Module Operator’s Guide, Section 3.2, Configuring the Separations Module.

3. Press the Dissolution screen key (or the More screen key to access the Dissolution screen key) to display the Dissolution System Configuration screen (Figure 4-5).

Figure 4-5 Dissolution System Configuration Screen

If one or two Hanson SR8-Plus baths are connected and powered on, the 2695D Separations Module recognizes the Waters Transfer Module and one or two Hanson SR8-Plus baths. If you using generic baths (non-Hanson bath systems), the 2695D Separations Module recognizes that no connection is present.

Note: The 2695D Separations Module does not communicate (software protocol) with generic bath systems.

4. Select the type of bath, SR8-Plus or Generic, from the Bath type drop-down list.

5. Select 1 bath or 2 baths from the number of baths field to the right of the Bath type field.

The ID, version number, and device number of the SR8-Plus bath(s) (if selected) are displayed in the dissolution instruments list.


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Note: To set the ID for a Hanson SR8-Plus, refer to the Hanson SR8-Plus Operational Manual. The 2695D Separations Module displays only the first six characters of the SR8-Plus ID.

6. To specify automatic vial scanning before any samples are collected, select the Scan vials before transfer check box.

To disable automatic vial scanning before any samples are collected, deselect the Scan vials before transfer check box.

7. Select the Recirculate media to vessels check box only if all the following conditions exist.

• You have configured your system for single-bath operation.

• You have fluidic tubing installed in your bath to enable this feature (single bath only).

• You plan to route the Dispenser Needle Body (Lower) tubing from the back of the 2695D Separations Module to the dissolution bath vessels (see Section 3.2.4, Connecting the Uni-Probes, the “Connecting the Recirculation Fluidic Lines” discussion).

Deselect the Recirculate media to vessels check box if you are routing the Dispenser Needle Body (Lower) tubing to waste.

In the Syringes field, the number 6 or 8 appears automatically depending on the number of syringes/needles in your dissolution system.

Note: The Waters Transfer Module must be powered on and connected to the 2695D Separations Module for the number of syringes to be displayed on the 2695D Dissolution System Configuration screen.

8. Press the Pill Drop screen key. The Pill Drop Options dialog box appears (Figure 4-6 and Figure 4-7).


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Figure 4-6 Pill Drop Options Dialog Box

Note: The selections in the Pill Drop Options dialog box apply to both stand-alone 2695D control and Millennium³² control of the dissolution system.

For each bath, select one of the following to control the 2695D Separations Module and the Millennium³² software for the pill drop portion of the dissolution test:

Bath Type - Generic or SR-8 with Manual Pill Drop

• User Prompt – Specifies that the dissolution test will begin only when you press OK in the Drop Dosage Form prompt. Refer to Section 6.1, Running the Dissolution Test.

Bath Type - Generic with Automatic Pill Drop

• On – Closes the selected switch at the start of the test (see the Waters 2695 Separations Module Operator’s Guide, Section 2.6.1, the “Event Switches” discussion). Enables you to select Switch 1, 2, 3, or 4.

• Off – Opens the selected switch at the start of the test (see the Waters 2695 Separations Module Operator’s Guide, Section 2.6.1, the “Event Switches” discussion). Enables you to select Switch 1, 2, 3, or 4.

• Toggle – Changes the state of the selected switch at the start of the test (see the Waters 2695 Separations Module Operator’s Guide, Section 2.6.1, the “Event Switches” discussion). Enables you to select Switch 1, 2, 3, or 4.

• Pulse – Closes, then opens the selected switch at the start of the test (see the Waters 2695 Separations Module Operator’s Guide, Section 2.6.1, the “Event


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Switches” discussion). Enables you to select Switch 1, 2, 3, or 4, and enables you to enter a pulse width in minutes.

• Switch 1-4 – Configures the I/O Function on the rear panel of the 2695D Separations Module. Select the appropriate Switch (1,2,3,4) from the drop down dialog box.

– Connect a Start Cable from the appropriate I/O Switch (1,2,3,4) terminals of the 2695D Separations Module to the sensing terminals of the pill drop assembly. Refer to the manufacturer’s instructions for connection to the pill drop assembly.

Hanson SR-8 Bath with Electric Probes and Pill Drop

• E-Probe – Configures the 2695D Separations Module for use with the Hanson SR-8 equipped with optional electric sampling probes. For automatic Pill Drop, select E-Probe from the drop down dialog box (Figure 4-7). This enables the 2695D Separations Module to communicate necessary signals to the electric probes motor controller for automatic pill drop.

Figure 4-7 Pill Drop Options Dialog Box with E-Probe Selected

4.1.2 Connecting Components when the 2695D Separations Module is the System Controller

When the Millennium³² software is not controlling the Alliance Dissolution System, the Waters Transfer Module is under control of the 2695D Separations Module.

• If you use Hanson SR8-Plus test baths, you can use the 2695D Separations Module to:

– Control bath temperature and paddle speed


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– Download other parameters

– Move dissolution samples through the system fluidic path (see Section 3.2, Connecting the System Fluidics)

• If you use generic baths, you can use the 2695D Separations Module only to move dissolution samples through the system fluidic path (see Section 3.2, Connecting the System Fluidics) and you can document bath temperature and paddle speed.

To control the detector from the 2695D Separations Module using the IEEE-488 cable, make the connections shown in Figure 4-1.

For more information on connecting the 2695D Separations Module to a detector using the IEEE-488 cable, see the Waters 2695 Separations Module Operator’s Guide, Section 2.7, Signal Connections, and the operator’s guide for the detector you use.

For information on making the RS-232 connections indicated in Figure 4-1, see Section 4.2, Making RS-232 Serial Port Connections.

For information on connecting the Alliance Dissolution System to the Millennium³² data system, see Section 4.1.3, Connecting Components when the Millennium³² Data System is the System Controller.

For information on controlling the dissolution system with the Millennium³² software, see the Millennium³² Software Getting Started Guide, the Millennium³² Dissolution System Software Quick Start Guide, and the Dissolution Overview topic in the Millennium³² Help.

4.1.3 Connecting Components when the Millennium³² Data System is the System Controller

You can control any system-compatible detector, including the Waters 486, 2487, or 996/2996 PDA detector, using the Millennium³² software.

To control the 2695D Separations Module and the detector and to record the detector’s output using the Millennium³² data system, make the connections shown in Figure 4-2.

To control the Waters 474 or any non-Waters detector, see Section 4.1.5, Using the busSAT/IN Module.

For details on connecting the 2695D Separations Module to a detector using the I/O cable, see the Waters 2695 Separations Module Operator’s Guide, Section 2.7, Signal Connections, and the operator’s guide for the detector you are using.

For information on making the RS-232 connections, see Section 4.2, Making RS-232 Serial Port Connections.


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4.1.4 Connecting to Generic Data Systems and to Generic BathsTo control the detector and record its output with a generic (non-Millennium³²) data system, make the connections shown in Figure 4-8. There is no control communications being exchanged between the 2695D Separations Module and generic baths.

Figure 4-8 Non-Millennium³² Data System Control of the Detector

You can connect the Waters 486 or 2487, or a non-Waters detector to another data system using analog or analog-to-digital signal connections.

For information on connecting a non-Waters detector to the Alliance Dissolution System, see the appropriate instrument operator’s guide.

For information on making Waters 486 or 2487 signal connections, see the Waters 486 Absorbance Detector Operator’s Guide or the Waters 2487 Dual λ Absorbance Detector Operator’s Guide.

For information on connecting the 2695D Separations Module to a detector using the I/O cable, see the Waters 2695 Separations Module Operator’s Guide, Section 2.6.1, Making I/O Signal Connections, and the operator’s guide for the detector you are using.

For information on making RS-232 connections, see Section 4.2, Making RS-232 Serial Port Connections.

4.1.5 Using the busSAT/IN ModuleTo use the Waters 474 detector or a non-Waters detector with the Alliance Dissolution System, you connect the detector using the Waters busSAT/IN module, as shown in Figure 4-9.

2695D Separations

Module


Generic Bath (A)

RS-232 Cable

Other Data System

(Fluidic ConnectionsOnly)

Generic Bath (B)

Waters 486, 2487, or Any Non-Waters

Detector

Inject Start (I/O) Cable

A/D Cable (Analog Signal)


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Figure 4-9 Millennium³² Control of the Waters 474 or Other Detector Using the busSAT/IN Module

For information on connecting the Waters 474 detector to the busSAT/IN Module and to the Millennium³² data system, see the Waters 474 Scanning Fluorescence Detector Operator’s Guide, Section 2.6, Making Connections to Other Devices.

For information on making RS-232 connections, see Section 4.2, Making RS-232 Serial Port Connections.

4.2 Making RS-232 Serial Port Connections

This section covers the procedures for making the RS-232 connections between components of the dissolution system.

Caution: Communication ports 1, 2, and 3 on the rear panel of the Waters Transfer Module (Figure 4-10) do not accept telephone-type modular connectors. Do not attempt to plug a modular telephone connector into any receptacle on the Transfer Module.

Waters busSAT/IN Module

2695D Separations

Module

Waters 474 or Any Non-Waters

Detector





RS-232 Cables (Suppliedby Hanson)

RS-232 Cable


Inject Start (I/O) Cable

Analog Signal Cable

Digital Signal Cable


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4.2.1 Connecting the 2695D Separations Module to the Waters Transfer Module

To connect the 2695D Separations Module to the Waters Transfer Module:

1. Locate the custom serial cable provided in the Waters Alliance Dissolution System Startup Kit (part number 200271886).

2. Connect the 9-pin connector end of the cable to the RS-232 AUX B port connector on the 2695D Separations Module (see Figure 4-3).

Figure 4-10 Waters Transfer Module Rear Panel Electrical Connections

3. Connect the RJ-12 (6-conductor) end of the cable to the COMM port 1 on the rear panel of the Waters Transfer Module (Figure 4-10).

4.2.2 Connecting Hanson SR8-Plus Baths to the Waters Transfer Module

To connect the Transfer Module to a Hanson SR8-Plus dissolution bath:

1. Locate the RS-232 serial cable provided with the Hanson dissolution bath.

2. Connect one end of the modular cable into COMM 2 on the Transfer Module (see Figure 4-10).

3. Connect the other end of the cable to COMM port 1 on Bath A.

4. If a second dissolution bath is to be connected to the system, plug one end of a second cable into COMM port 2 on Bath A.

5. Plug the other end of the cable into COMM port 1 on Bath B.

COMM

1 2 3

CP

U F

UN

CT

ION

AUXILIARYI/O

TP01545

3A TT FUSE

To COMM Port 1on Hanson SR8-Plus

Bath A

To RS-232 AUX Bon 2695D

(For Future Use)

Fuse

Connection toPower Module

Making RS-232 Serial Port Connections 79

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For information on connecting ancillary equipment, such as a printer, to a Hanson SR8-Plus bath, see the Hanson SR8-Plus Operational Manual.

4.2.3 Connecting Printers in the Alliance Dissolution SystemTo obtain printed reports, you must connect a printer to the 2695D Separations Module or to a Hanson bath system, if installed. For printing chromatography test results, you must connect a printer to the Millennium³² data system.

To connect a printer to:

• The 2695D Separations Module, see the Waters 2695 Separations Module Operator’s Guide, Section 2.7, Signal Connections. This connection requires an RS-232 cable.

• The Hanson bath system, see the Hanson SR8-Plus Operational Manual.

• The Millennium³² data system, see the Millennium³² System Installation and Configuration Guide.


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Chapter 5Setting Up the Dissolution System

This chapter covers:

• Starting up the Alliance Dissolution System

• Preparing the dissolution instruments for testing

• Developing dissolution methods

See Chapter 6, Making a Run, for information on making a dissolution run and on monitoring the system status during a run.

Note: To operate the dissolution system, you need to become familiar with the operation of the 2695 Separations Module. For information on the 2695 Separations Module, see the Waters 2695 Separations Module Operator’s Guide.

Before you proceed with the setup procedures in this chapter, you must complete the:

• Electrical power connections described in Section 2.3, Making Electrical Power Connections

• Fluidic connections described in Section 3.2, Connecting the System Fluidics

• Signal connections for your system described in Chapter 4, Configuring Components

5.1 Starting Up the Dissolution System

Starting up your dissolution system involves:

• Powering on each instrument

• Checking startup diagnostics

• Ensuring the 2695D configuration parameters are correct.

Powering On

Power on each instrument in your Alliance Dissolution System by turning the On/Off switch to the On (I) position. The On/Off switches are located as listed in Table 5-1.

Starting Up the Dissolution System 81

5

Table 5-1 Alliance Dissolution System Devices Power Switch Locations

Note: You do not need to power on the Waters Transfer Module or the Hanson SR8-Plus dissolution test bath(s) before you initialize the 2695D.

Startup Diagnostics

During startup, the 2695D firmware:

• Runs the startup diagnostics, which include the startup diagnostics for the 2695 separations module (see the Waters 2695 Separations Module Operator’s Guide, Chapter 3, Preparing the 2695 Separations Module for Operation)

Note: AutoStartPLUS is a preprogrammed startup method that is provided with the 2695D Separations Module beginning with firmware version 1.0. Refer to the Waters 2695 Separations Module Operator’s Guide for details.

• Checks for the presence of the Dissolution Dispenser in the 2695D Separations Module.

• Homes the Dissolution Dispenser (to the top position).

Once homing is successfully completed, the dissolution option is recognized and the 2695D Separations Module’s Main screen (Figure 5-1) is displayed. If homing is not successful, an Error message is displayed (see Table 8-1).

2695D Separations Module Top left side panel

Waters Transfer Module Top right side panel

Hanson SR8-Plus Top right rear side panel. Follow the instructions in the Hanson SR8-Plus Opera-tional Manual.

Waters 486, 2487, 996/2996, or 474 detector See the applicable detector operator’s guide.

Other manufacturers’ baths, detectors, and instruments used with the dissolution system

See the operator’s guide for the equipment you are using.

82 Setting Up the Dissolution System

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Figure 5-1 Dissolution System 2595D Main Screen

Checking the 2695D Configuration

To check which options are installed in the 2695D Separations Module, access the Installed Options dialog box by pressing Config, More, then Options from the 2695D Main screen.

If the 2695D startup diagnostics routine detects the Dissolution Dispenser, the Dissolution check box is selected in the Installed Options dialog box, along with the other options configured with your system (for example, column heater and inline degasser).

Note: The 2695D AutoStartPLUS feature does not function under remote control configurations. When using AutoStartPLUS, the instrument must be configured for standalone operation. Refer to the Waters 2695 Separations Module Operator’s Guide.

5.2 Preparing for Dissolution Testing

STOPAttention: To avoid damaging the 2695D Dissolution Dispenser, use only pre-slit septa on the vials (see Appendix B, Spare Parts), and do not use low-volume inserts. Use only opaque vial caps to ensure that vial scanning operates properly.

Preparing for Dissolution Testing 83

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After you power on the instruments in your dissolution system, you need to set up each instrument. This section describes setting up the:

• Waters 2695D Separations Module

• Waters Transfer Module

• Hanson SR8-Plus or other generic dissolution bath

• Detector

• Millennium³² software (for system control, data processing and analysis, or for data analysis only)

Required Materials

• 2-mL sample vials with pre-slit septa and opaque caps, as needed for your dissolution method(s)

• Fresh mobile phase, 1 L

• HPLC-grade water

• Dissolution media, 15 mL per fluidic line

To perform chromatography associated with dissolution sample analysis, be sure to equilibrate the 2695D with fresh mobile phase (see the Waters 2695 Separations Module Operator’s Guide, Section 4.4, Performing Direct Functions).

Note: Before you operate the dissolution system for the first time, be sure to prime each fluidic line with at least 15 mL of dissolution media to ensure consistent and accurate test results.

5.2.1 Setting Up the 2695D Separations ModuleTo set up the 2695D Separations Module for dissolution testing:

1. Prepare the required number of 2-mL dissolution sample vials by inserting the caps onto vials with pre-slit septa. To facilitate vial scanning, use only opaque caps on the vials in the 2695D sample compartment.

2. Load the assembled vials into the 2695D sample carousel (see the Waters 2695 Separations Module Operator’s Guide, Section 4.2, Loading Sample Vials).

3. Depending on your system configuration:

• Develop one or more dissolution methods using the 2695D front panel interface. For information on developing methods using the 2695D front panel interface, see Section 5.3, Developing a Dissolution Method.

• Develop one or more sample sets for dissolution testing using the Millennium³² Dissolution software option. For information on developing methods using the


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Millennium³² software, see the Millennium³² Software Getting Started Guide and the Millennium³² Dissolution System Software Quick Start Guide.

5.2.2 Setting Up the Waters Transfer ModuleBefore you run a dissolution test, you need to set up the Waters Transfer Module and ensure that the syringes are operating wet and bubble free.

Setting up the Waters Transfer Module involves:

• Priming the syringes and valves at system startup

• Washing the syringes after each run

Priming the Transfer Module

Before you operate the Alliance Dissolution System for the first time, prime the Transfer Module. You can use the Wash Station supplied with the Uni-Probes (Figure 5-2) or separate beakers filled with the media you plan to use in your dissolution testing.

Note: Before you begin priming, flush the Transfer Module several times to waste.

If you use the Uni-Probe wash station to prime the Waters Transfer Module, fill it with at least 2 L of dissolution media, then insert the Uni-Probes, as shown in Figure 5-2.

Figure 5-2 Uni-Probe Wash Station Set Up to Prime Transfer Module

TP01570

Uni-Probes

Dissolution Media

WashStation


5

To prime the Waters Transfer Module:

1. Route the tubes labeled Dispenser Needle Body (Lower) from the 2695D to waste.

2. Ensure the Uni-Probe wash station, beaker, or other appropriate vessel is filled with at least 2 L of the dissolution media you plan to use [fill the wash station with 2 to 3 inches (5.0 to 7.6 cm) of media].

3. If you use the Uni-Probe wash station, connect the Uni-Probes to the Transfer Module by following the color codes provided in Table 3-1.

4. From the 2696D Separations Module Main screen, press Menu/Status to display the Status screen.

5. Press the Direct Functions screen key.

6. Select Set Up Transfer Module from the Direct Functions menu (Figure 5-3), then press OK. The Set Up Transfer Module dialog box is displayed (Figure 5-4).

Note: The bottom portion of the wash station can be placed under the electric probes for washing or priming.

Figure 5-3 Direct Functions Menu Screen


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Figure 5-4 Set Up Transfer Module Dialog Box

7. Enter the priming volume (per syringe) in the Volume field.

8. Press the appropriate screen key:

• Prime Bath A – To prime the fluidics from Bath A to the Transfer Module syringes, then to waste.

• Prime Bath B – To prime the fluidics from Bath B to the Transfer Module syringes, then to waste.

• Prime Line C – To prime the fluidics from wash or media replace to the Waters Transfer Module, then to waste.

The Wash All screen key is used to automatically wash all fluidic lines, syringes, and needles in the system after a run. For more information, see Section 7.2.4, Maintaining Other Parts of the Dissolution System, the “Washing the Transfer Module” discussion.

Note: You can also use the Fill and Dispense diagnostics to prime the Transfer Module syringes before running a dissolution test or to troubleshoot the Dissolution Dispenser or Transfer Module syringes (see Section 8.2.3, Performing Transfer Module Diagnostics, the “Using the Fill and Dispense Diagnostics” discussion).

5.2.3 Setting Up the Dissolution Test BathTo set up the dissolution test bath:

1. Fill the bath with HPLC-grade water according to the instructions in the bath manufacturer’s operator’s guide.


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2. Fill each dissolution vessel to be used for the dissolution test with media (filtered and degassed) according to the dissolution method in use.

3. Install a filter on each probe. Refer to Section 3.2.4.

4. Install one Uni-Probe for each dissolution vessel and connect each Uni-Probe to the Transfer Module syringes (see Figure 1-8 and Section 3.2.4, Connecting the Uni-Probes).

5. Attach each Uni-Probe to its cover assembly (see Section 3.2.4, Connecting the Uni-Probes) and place on top of the dissolution vessel.

6. If you are recirculating media to the dissolution vessels, adjust the height of the recirculation assembly so that the tube is above the media level (see Figure 3-6 and Section 3.2.4, Connecting the Uni-Probes, the “Connecting the Recirculation Fluidic Lines” discussion).

7. To start up and bring the Hanson SR-8 dissolution bath up to temperature:

• Refer to the instructions provided within the Hanson manual.

• Access the Disso Method to set the speed for the dissolution paddles at the 2695D.

• Access the Disso Method to set the temperature of the bath at the 2695D .

If you are using another manufacturer’s bath, set the temperature and paddle speed controls manually, according to the manufacturer’s operating manual.

8. Allow sufficient time for the dissolution medium to reach the required test temperature. This can take up to 2 or more hours.

Note: To prevent bubbles that may cause erroneous dissolution data and to ensure accurate injection volumes, degas the dissolution vessel media. For more information on degassing the dissolution vessel media, see the operator’s guide for the bath(s) you are using.

5.2.4 Setting Up the DetectorFor information on installing, configuring, and setting up your dissolution system detector, refer to the applicable detector operator’s guide. In your dissolution system, perform one of the following:

• Connect the Waters 486 or 2487 detector to the 2695D separations module through the signal ports shown in Figure 4-3 or by using the IEEE-488 interface, the busSAT/IN module, or the I/O connector to input an inject start signal. For more information, see the Waters 486 Absorbance Detector Operator’s Guide or the Waters 2487 Dual λ Absorbance Detector Operator’s Guide.

• Connect the Waters 474 detector or a third-party detector to a data system through the busSAT/IN module (see the Waters 474 Fluorescence Detector Operator’s Guide


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or the operator’s guide for the third-party detector) using the 2695D I/O connectors to input an inject start signal.

• Connect the Waters 996/2996 PDA detector to Millennium³² software using an IEEE-488 cable using the 2695D I/O connectors to input an inject start signal to the 996/2996 (see the Waters 996 PDA Detector Operator’s Guide or the Waters 2996 PDA Detector Operator’s Guide).

5.2.5 Setting Up the Millennium³² Software

Note: To operate the Alliance Dissolution System for dissolution methods development and testing using the Millennium³² software, you must install the Millennium³² Dissolution software option.

To set up the Millennium³² software to acquire, process, review, and report data from the Alliance Dissolution System, refer to the Millennium³² Getting Started Guide, the Millennium³² Dissolution System Software Quick Start Guide, and the Millennium³² Help.

5.3 Developing a Dissolution Method

To operate the dissolution system you need a dissolution method. A dissolution method is a sample set that specifies the parameters for dissolution testing.

The dissolution method is not bath specific. You can use the same dissolution method for both baths in a dual-bath system, or use different methods for each bath. The 2695D or the Millennium³² software automatically calculates minimum time differences between sample transfers to ensure that the methods for the two baths do not overlap.

5.3.1 Developing a New Dissolution MethodYou can develop a new dissolution method for:

• Standalone operation of the 2695D – If you use the 2695D front panel to develop a dissolution method, become familiar with the Waters 2695 Separations Module Operator’s Guide, Section 5.1, Making Automatic Runs in Stand-Alone Mode, and Chapter 6, Creating Methods, Sample Sets, and Sample Templates.

• Remote control (Controlled by Millennium³²) – If you use the Millennium³² software to develop a dissolution method (that is, a sample set method), refer to the Millennium³² Dissolution System Software Quick Start Guide and the Creating a Sample Set Method in Run Samples Using the Wizard topic in the Millennium³² Help.

Note: The 2695D AutoStartPLUS feature does not function under remote control configurations. When using AutoStartPLUS, the instrument must be configured for standalone operation. Refer to the Waters 2695 Separations Module Operator’s Guide.

Developing a Dissolution Method 89

5

To develop a dissolution method for standalone operation of the 2695D:

1. From the Main screen (Figure 5-1), press the Develop Methods screen key, then press New. The Create New Method dialog box is displayed (Figure 5-5).

Figure 5-5 Create New Method Dialog Box

2. Press the Dissolution method screen key. The Dissolution Method Name dialog box is displayed (Figure 5-6).

Figure 5-6 Dissolution Method Name Dialog Box


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3. Enter the name of your dissolution method (for more information, see the Waters 2695 Separations Module Operator’s Guide, Section 3.1, Operating Overview), then press Enter. The Dissolution Method Parametric View is displayed (Figure 5-7).

4. Enter or change the entries in the Parametric View fields according to the information provided in Table 5-2.

Figure 5-7 Dissolution Method Parametric View Screen

Note: If Replace media is selected in the Parametric View (see Figure 5-7), then after each sample is taken, the Alliance Dissolution System replaces the total volume removed from the dissolution vessels with fresh media.

Table 5-2 Parametric View Screen Fields

Field Description Useful Range

Dissolution vessel media Displays a list of media used in the dissolution vessels

Use the Labels screen key to display or add to the list of media names.

Needlesa Displays number of Disso-lution Dispenser needles in the 2695D

Displays 6 or 8. This number must correspond to the number of syringes in the Transfer Module and the number of needles in the Dissolution Dispenser.


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Use vessels Displays the range of vessels to be analyzed

Enter numbers between 1 and 6 or 1 and 8 (depending on the number of needles in the 2695D Dissolution Dispenser)

Transfer ModuleVolume

Displays the volume to be removed from each disso-lution vessel and transfer to a vial at programmed intervals

0.8 to 1.5 mL

Transfer ModuleSample vials

Alpha-numeric listing of sample vials in 2695D

Choices are based on number of vessels and number of programmed samples

Transfer ModuleReplace media

When selected, instructs the Transfer Module to replace all media taken from vessels with fresh media through Valve C

Selected – Activates replace media activity

Not selected – Media is not replaced

Bath ConditionsTemp

Allows you to document the temperature of the dissolu-tion bath(s) or to control Hanson SR8-Plus bath(s)

30 to 40 °C

Bath Conditions(Paddle) Speed

Allows you to document the speed of the paddles in the dissolution bath(s) or to control Hanson SR8-Plus bath(s)

25 to 200 rpm

Pooled SamplesPool vessels

When selected, allows sample pooling from disso-lution vessels

Selected – Activates the other pool fields

Not selected – Entry to other pool fields is disabled

Pooled Samples(Vessel Range)

The range of vessels from which to pool samples for a single injection. Type a decimal point to display a hyphen (e.g., type 2.5 to display 2–5).

Range of vessels as a subset of the number of vessels in the system. For example, in an eight-vessel system, the range may be 1–6.

Table 5-2 Parametric View Screen Fields (Continued)



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5. Press the Sample Timing screen key. The Dissolution Sample Timing Dialog Box is displayed (Figure 5-8). Refer to Table 5-3 for a description of dissolution sample timing parameters.

Note: The time interval between two consecutive samples cannot be less than 2.0 minutes. The first sample can be drawn as early as 1.0 minute.

6. Enter in the Samples time points table the time at which each sample is to be removed.

Figure 5-8 Sample Timing Dialog Box

7. In the Test length field, enter the total time for the test.

Pooled Samplesb

Volume from eachVolume taken from each vial for pooling in the sample loop

1 to 10.0 µL

Pooled SampleDelay (before injection)

Amount of time to wait after drawing pooled sample from all vials before making an injection

0 to 10 min.

a. Defaults to the number of syringes in your system. You can use a different number if you are creating a method for export to another dissolution system.

b. The total pooled sample volume cannot exceed the capacity of the sample loop.

Table 5-2 Parametric View Screen Fields (Continued)


Samples Timing Table


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8. If you are using the Hanson SR8-Plus, in the Infinity test field, enter the time after the total test length during which the paddle runs at 250 rpm.

An infinity test operates the paddle at 250 rpm for a specified period of time following completion of testing at a slower paddle speed. At the end of the 250 rpm period, an additional sample is transferred (even if you are using a generic bath).

9. Select the Collect all samples before any LC check box if you want the 2695D to wait for all samples to be collected before injecting the first sample.

10. Press OK when you complete filling in the fields in the Dissolution Sample Timing dialog box (or press Cancel).

Note: Separation conditions are the injection parameters for each sample in the dissolution method.

11. Press the Separation Conditions screen key to display the Separation Conditions dialog box (Figure 5-9). Table 5-4 describes the parameters, ranges, and limits for the Separation Conditions dialog box.

Table 5-3 Sample Timing Parameters

Parameter Description Useful Range

Samples List of sample time points, up to 20

At least one entry must be present in the Samples timing table. Range = 1.0 to 20.0

Test length Specifies the total time of test, not including optional infinity test

1 to 7200 min.

Infinity test Specifies how long to run the paddles at 250 rpm (paddle control for Hanson SR8-Plus only) after the test length.

2 to 30 min.

Collect all samples before any LC

Specifies whether chromato-graphic analysis is performed between sample collections or after all samples are collected (normally not checked).

Selected – Defers LC until all samples are collected

Not selected – LC is performed between sample collections


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Figure 5-9 Separations Conditions Dialog Box

12. In the Function drop-down list, select Sample or Auto Add (see Table 5-4).

13. In the Separation Method drop-down list, select the separation method.

14. In the Number of Injections field, enter the number of injections per sample.

15. In the Total injection volume field, enter the total volume for each injection.

16. In the Run time field, enter the run time for the chromatographic separation of the collected samples.

17. Select the Use vial ranges check box if you want a sample set with injections expressed in a range of vials instead of vial-by-vial. Deselect the Use vial ranges check box if you want each vial in the carousel to occupy a line in the sample set.

18. Press OK to complete entry of the Separation Conditions (or press Cancel).

Table 5-4 Separations Conditions Di a l o g B o x P a r a m e t e r s


Function If you select Auto Add, you need to specify additional parameters. See the discussion “Auto Add” in the Waters 2695 Separations Module Operator’s Guide, Section 6.3.1, Functions

Sample or Auto Add

Separation method Lists available separation methods

Select from list


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19. Press the Misc Options screen key to display the Miscellaneous Options dialog box (Figure 5-10). Table 5-5 provides the parameters, descriptions, and ranges or limits for the Misc Options dialog box.

Figure 5-10 Miscellaneous Options Dialog Box

20. If you use the Hanson SR8-Plus, select the desired option from the Out of USP tolerance alarm drop-down list.

See the Waters 2695 Separations Module Operator’s Guide, Section 6.2, Setting Separation Module Parameters, and the Hanson SR8-Plus Operational Manual for more information.

21. If you use a printer connected to a Hanson SR8-Plus, enter a number in the Auto print interval field (refer to the Hanson SR8-Plus Operational Manual).

Number of injections Specifies the number of injections per sample, or auto add

1 to 10

Injection volume Specifies the volume for each injection

0 to 100 µL

Run time Specifies the run time for data acquisition following injection

0 to 30 min

Use vial ranges Specifies a range of vials on each line in the sample set instead of individual vials, one per line

N/A

Table 5-4 Separations Conditions Dialog Box Parameters (Continued)



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22. In the Transfer Module Pre-sample rinse field, enter a volume for the automatic rinse between samples.

23. In the Transfer Module Post-sample wash field, enter a volume for the automatic rinse after samples.

24. Select Recirculate media if your dissolution system is configured to return media to vessels after each sample is dispensed (single-bath systems only).

Note: When Recirculate media is selected, the Transfer Module Post-sample wash option is disabled.

25. Select the appropriate syringe speed. This option is useful when sample viscosity is too dense for the normal syringe speeds.

26. Select Rapid sampling for faster sampling times (single-bath systems only).

Table 5-5 Miscellaneous Options Di a l o g B o x P a r a m e t e r s


USP out-of-tolerance alarm

Applies only to Hanson SR8-Plus baths. If this alarm is selected and the SR8-Plus detects an out-of-tolerance condition, the spec-ified response occurs. See the Hanson SR8-Plus Operational Manual for USP tolerance guidelines.

(See the Waters 2695 Separa-tions Module Operator’s Guide, Section 6.2, Setting Separation Method Parameters.)

Auto print interval

Applies only to printers connected to the Hanson SR8-Plus.

0.1 to 30 or OFF

Pre-sample rinse

Provides the volume for the auto-matic rinse between samples. The rinse volume is the total volume dispensed before expelling the programmed sample volume to the vials.

2.5 to 15.0 mL (typical entry)

Post-sample wash

Provides the volume for the auto-matic rinse after samples. The rinse volume is the total volume dispensed after expelling the programmed sample volume to the vials.

2.5 to 15.0 mL

Syringe speed Allows the user to choose the speed that the syringe draws the sample.

Normal or Slow


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27. Press the Document screen key to display the Method Documentation dialog box (Figure 5-11).

28. Select each field you want to change, press the Modify screen key, then enter or change the information.

Recirculate media

This option applies to single bath systems only. Specifies recircula-tion of sampling media to bath. See the discussion “Connecting the Recirculation Fluidic Lines” in Section 3.2.4, Connecting the Uni-Probes.

Selected – Media is recircu-lated to dissolution vessels(if your system is configured for media recirculation).

Not selected – System is not configured for media recircula-tion. Sampled media is dispensed to waste.

Rapid sampling Applies to single-bath systems only. A minimum 2.5 mL rinse occurs between sample sets; the programmed rinse volume applies to the first sample set only. This allows faster sampling times.

Selected – A minimum 2.5 mL volume rinse between sample sets is performed.

Not selected – The program-med rinse volume is used to perform a rinse before each sample is transferred. If the programmed rinse volume is too large, you may have to change the sample timing.

Table 5-5 Miscellaneous Options Dialog Box Parameters (Continued)



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29. Press OK when you complete your entries (or press Cancel).

Figure 5-11 Dissolution Method Document Dialog Box

5.3.2 Reviewing and Customizing Your Dissolution Method

Displaying Views

By pressing the Next View screen key in the Dissolution Method screen, you can display the dissolution method in any of the four views described below. Only the Parametric View is unique to the dissolution software.

Parametric View – Displays the basic dissolution method parameters as shown in Figure 5-7 through Figure 5-10. In this view, you specify the parameters to create your dissolution method (sample set table).

Functional View – Displays the dissolution method with one function per line, as shown in Figure 5-12. This view gives you an overview of the run, including vial ranges and any linked rows. You can edit some of the separation conditions for your dissolution method from the Functional View. This allows you to insert standards and other fluidic functions (such as Equilibrate and Purge) into the method.

Injection View – Displays the dissolution method with one injection per line, as shown in Figure 5-13. Pressing the Injects Only screen key displays only those lines that represent an injection. This list corresponds to chromatograms produced by the run.

Loading View – Displays the dissolution method with one vial per line, as shown in Figure 5-14. This view shows you how to load the samples and empty vials in the carousels.


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Figure 5-12 Dissolution Method Functional View Screen

Figure 5-13 Dissolution Method Injection View Screen


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Figure 5-14 Dissolution Method Loading View Screen

Inserting Functions

The Aliquot function (see Figure 5-12) is not a fluidic function as are the other functions in the table. You can change an aliquot only from the Sample Timing dialog box of the Parametric View (see Figure 5-8).

In Figure 5-12, the “vials” column of Line 1 shows the vials to be filled by transfers from the Transfer Module. The “min” column in Line 1 shows the dissolution sample time after the time at which the dosage form is dropped into the dissolution vessel.

The 2695D performs no functions after the Aliquot function until the Transfer Module has filled the vials as indicated. If you want to ensure that a function is performed as closely as possible to the aliquot samples, insert the function after the Aliquot row, as illustrated by the Standards function in Row 2 of Figure 5-12.

For more information on the Functional, Injection, and Loading views of the 2695D, see the Waters 2695 Separations Module Operator’s Guide, Section 5.1, Making Automatic Runs in Stand-Alone Mode.

Programming Auto Standards

The Auto Standards function in the function drop-down list (Figure 5-12) allows you to run standards repetitively from one or more standards vials after a specified number of vials or injections.


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To use the Auto Standards function:

1. Select AutoStds from the drop-down list of functions, then press the Row Details screen key to display the Auto Standards dialog box (Figure 5-15).

Figure 5-15 Auto Standards Dialog Box

2. In the Run standards every field, enter a number for one of the following parameters, for example, Run standards every: 3 vials, as shown in Figure 5-15):

• injects

• vials

• injects/bath

• vials/bath

3. In the Source Vial(s) table, enter a vial number and total volume (in µL) for each of the standards vials. You can specify multiple standards vials to support large runs.

4. Select the Run preliminary standards check box to run standards before the first sample is injected. Deselect the Run preliminary standards check box if you want to program other injection types (for example, System Suitability) at the beginning of the dissolution sample set. The default is selected.

5. Select the Hold standards until first aliquot transfer check box if you want the 2695D to wait until just before sample injection to inject the first standard. If you run preliminary standards, you can deselect the Hold standards until first aliquot transfer check box to run the standard(s) immediately at the start of the test. The default is selected. The Hold standards until first aliquot transfer check box is automatically deselected if the Run preliminary standards check box is deselected.


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6. Select the Always run standards after the final inject check box if you want to run standards after the last sample injection regardless of the number of vials (or injections) you specify in the Run standards every field. The default is deselected.

Note: The Always run standards after the final inject function is useful if you have a total number of samples that is not divisible by the number specified in the Run standards every field. For example, if the total number of sample injections in your sample set is 8 and you specify Run standards every 3 vials, the standard is run after the final two vials (3 + 3 + 2) only if you select the Always run standards after the final inject check box.

For more information on Auto Standards, see the Waters 2695 Separations Module Operator’s Guide, Section 6.3.1, Functions, the “Auto Standards” discussion.

5.3.3 Sample PoolingIn the Pooled Samples section of the Dissolution Method Parametric View (Figure 5-16) you specify the parameters for combining samples from multiple vials in the 2695D carousel into a single (multiple-sample) injection onto the column.

1. To make entries in the fields in the Pooled Samples section, select the Pool vessels check box in the Parametric View screen (see Table 5-2).

• The first (top) field specifies the range of sample vessels to be pooled.

• The Volume from each field specifies the volume (1 to 10.0 µL) to be collected from each vial. When all volumes are collected, the pooled sample is injected onto the column.

• The Delay field specifies a delay to allow the pooled sample to mix before being injected onto the column. See the Waters 2695 Separations Module Operator’s Guide, Section 6.3.1, Functions, the “Auto Add” discussion.


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Figure 5-16 Dissolution Method Parametric View with Pooling Enabled

2. Press the Next View screen key to review and/or customize your dissolution method using the Functional View (Figure 5-17).

Figure 5-17 Dissolution Method Functional View with Pooling Enabled

5.3.4 Saving a Dissolution Method as a Sample SetAfter you create a dissolution method, you can save it for use on the originating Alliance Dissolution System or for export to another system.

SamplePooling

Parameters


5

To save a dissolution method as a sample set:

1. From the Main screen, press the Develop Methods screen key.

2. Select a dissolution method, then press the More screen key. A different set of screen keys is displayed (Figure 5-18).

Figure 5-18 Making a Sample Set from a Dissolution Method

3. Press the Make SS screen key. The Make Sample Set prompt appears (Figure 5-19).

4. Enter a name for the new sample set, then press Enter.


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Figure 5-19 Naming the Sample Set

For more information, see the Waters 2695 Separations Module Operator’s Guide, Section 3.1, Operating Overview.


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Chapter 6Making a Run
This chapter describes how to run dissolution tests using the Alliance Dissolution System under control of the Waters 2695D Separations Module.

If you are running dissolution tests under control of the Millennium³² software:

1. Prepare the dissolution system as you would for 2695D control (see Section 6.1, Running the Dissolution Test, the “Before You Begin” discussion below).

2. Refer to the Millennium³² Dissolution Software Quick Start Guide and the Dissolution Overview topic in the Millennium³² Help.

6.1 Running the Dissolution Test

Before You Begin

Before you can run a dissolution test with the Alliance Dissolution System, you need to:

• Have at least one dissolution method available in the 2695D separations module or the Millennium³² data system (see Section 5.3.1, Developing a New Dissolution Method).

• Equilibrate the bath temperature (see the documentation for the bath you use).

• Equilibrate the HPLC system (see the Waters 2695 Separations Module Operator’s Guide, Section 4.4, Performing Direct Functions).

• Set up the 2695D (see Section 5.2.1, Setting Up the 2695D Separations Module).

• Prime the Transfer Module (see Section 5.2.2, Setting Up the Waters Transfer Module).

6.1.1 Making a Run Under 2695D ControlTo run a dissolution test under 2695D control (for either a single- or a dual-bath system):

1. From the 2695D Main screen, press the Run Samples screen key to display the Run Samples screen (Figure 6-1).

Running the Dissolution Test 107

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Figure 6-1 Run Samples Screen

The method types displayed in the Run Samples screen are indicated by icons, as shown in Table 6-1.

Note: Not all method types may be displayed.

2. Select the dissolution method you want to run.

3. To perform an automatic scan for required vials, press the Scan Vials screen key. The 2695D software scans all vials, checks for the vials required for the test, then displays the results (for details, see Section 6.1.4, Scanning for Required Vials).

Table 6-1 Method Icons

Icon Description

Separation method

Dissolution method

Sample seta

a. Not used for dissolution

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4. If you have not already established the initial conditions (bath temperature, flow rate, sample chamber temperature, and so on) for the selected dissolution method, press the Initial Conds screen key (for details, see Section 6.1.5, Applying Initial Conditions).

Note: You must press Initial Conds before you start a run, unless you enter the initial conditions for the run in the first row(s) of the dissolution method using the Equil or Condition function.

5. To print the requirements for the selected dissolution method, press the Print screen key (Figure 6-2). To print from the 2695D, you must have a formatted 3.5-inch floppy disk inserted in the 2695D disk drive or a printer connected to your system. See also Section 6.1.6, Printing Dissolution Reports.

6. Press the Run screen key to begin the dissolution test run. The Requirements screen for a single-bath (Figure 6-2) or dual-bath (Figure 6-4) system is displayed.

7. If you use a single-bath system, proceed to Section 6.1.2, Making a Run Using a Single-Bath System. If you use a dual-bath system, proceed to Section 6.1.3, Making a Run Using a Dual-Bath System.

6.1.2 Making a Run Using a Single-Bath SystemThis section describes how to run a dissolution test using a single-bath system starting from either of the following:

• With on-line samples by the Waters Transfer Module

• Previously prepared samples

Figure 6-2 Single-Bath Requirements Screen


6

Before You Begin

Follow the procedures in Section 6.1.1, Making a Run Under 2695D Control.

Procedure

To run a dissolution test when the 2695D is configured to prompt you to drop dosage forms (see Section 4.1.1, Configuring the 2695D Separations Module):

1. Press the Routine screen key. A message prompts you to drop the dosage forms into the vessels in Bath A.

Note: The message prompt will not appear when the system is configured for automatic pill drop.

2. Press OK to continue the test (or press Cancel to stop the test).

The banner at the top of the 2695D screen displays the progress of the test.

Note: You can monitor the test on the Status screen by pressing the Menu Status key (see Section 6.2, Monitoring Dissolution System Status).

To run a previously prepared dissolution sample set:

1. Check that there are no empty vials in the range covered by the dissolution method or sample set.

2. Press the Skip Trans screen key (Figure 6-2). This function omits the sample dissolution and transfer phases of a dissolution test and re-analyzes a completed dissolution test

6.1.3 Making a Run Using a Dual-Bath SystemThis section describes how to run a dissolution test using a dual-bath system starting from either of the following:

• With on-line samples by the Waters Transfer Module

• Previously prepared samples

Before You Begin

Follow the procedures in Section 6.1.1, Making a Run Under 2695D Control.

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Procedure

To run a dissolution test in a dual-bath system when the 2695D is configured to prompt you (User Prompt) to drop dosage forms (see Section 4.1.1, Configuring the 2695D Separations Module):

1. Select a dissolution method (the dissolution method for the first bath) from the Run Samples screen (see Figure 6-1), then press Run.

The Dual Bath Setup screen is displayed (Figure 6-3). The method name field for both baths defaults to the method you selected in step 1.

Figure 6-3 Dual Bath Setup Screen

2. If desired, select a different method name in the field for either bath, or press Clear to select <Not Used>.

3. Select the correct vial ranges from the drop-down lists for both baths.

Note: Because the Alliance Dissolution System software interleaves the LC samples from both methods into a single sample set, the vial ranges for both baths must not overlap.

4. In the Delayed start field, enter a time to delay drawing the first sample from the second bath, or press the Min Delay screen key.

The Waters Transfer Module can transfer samples from only one bath at a time. Depending on the dissolution method(s) you select, the Transfer Module may transfer one or more samples from the first bath before transferring samples from the second bath.

BATH A BATH B


6

Note: The bath with the delayed start is the bath from which samples are transferred to higher-numbered vials (vials in carousel A are lower-numbered than vials in carousels B, C, D, or E).

5. Press Min Delay to have the 2695D software automatically calculate the minimum amount of time after the sample transfer from the first bath at which the sample transfer from the second bath can start.

6. Press OK to continue the dual-bath dissolution test using the selected methods, vial ranges, and delay time (or press Cancel to stop the test).

When you press OK, the Dual-Bath Requirements screen (Figure 6-4) displays:

• Names for the first and second baths (default: Bath A and Bath B)

• Dissolution media you entered in the Method Documentation screen (see Figure 5-11)

• LC solvents used in the 2695D

Figure 6-4 Dual Bath Requirements Screen

7. Press Routine. A message prompts you to drop dosage forms into vessels in Bath A, (Figure 6-5). Bath A is the first bath in the dissolution method, that is, the bath from which the Transfer Module transfers samples to the lower-numbered vials in the 2695D sample compartment.

Note: The message prompt will not appear for systems configured for automatic pill drop.

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Figure 6-5 First Drop Dosage Forms Prompt for Dual-Bath System

8. Press OK after you drop the dosage forms into the vessels of the first bath.

Note: You can press the Menu/Status key to monitor the progress of the test in the Status screen (see Section 6.2, Monitoring Dissolution System Status).

When the start delay time elapses, a second message (Figure 6-6) prompts you to drop dosage forms. The timer at the bottom of the prompt screen starts at 30 seconds and counts down to zero, indicating the time remaining to drop the dosage forms into the vessels of the second bath.

9. Drop the dosage forms into the dissolution vessels of the second bath and press OK before the 30-second timer reaches zero to continue the dual-bath test (or press Cancel to stop the test).

Note: If you press Cancel or if you do not drop the dosage forms within 30 seconds, the dissolution method for the first bath continues to run as if you were performing dissolution testing on a single bath.

STOPAttention: You must drop the dosage forms into the second bath within theallotted 30 seconds. If you do not press OK before the second bath counterreaches zero, you cannot continue the test with the second bath.


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Figure 6-6 Second Drop Dosage Forms Prompt for Dual-Bath System

To run a previously analyzed dissolution method or sample set:

1. Check that there are no empty vials in the range covered by the dissolution method or sample set.

2. Press the Skip Trans screen key (Figure 6-4). This function omits the sample dissolution and transfer phases of a dissolution test and re-analyzes a completed dissolution test

6.1.4 Scanning for Required VialsThe Scan Vials function in the Alliance Dissolution System allows you to automatically scan the required vials in the 2695D carousels to verify that you have loaded the carousels correctly (for the selected dissolution method).

You can specify automatic vial scanning in two ways:

• When you configure the 2695D:

a. Select the Verify vial presence check box in the Configuration screen (see Figure 4-4) to select the Scan vials before transfer check box (see Figure 4-5).

b. Select the Scan vials before transfer check box in the Dissolution Configuration screen (Figure 4-5) to check for the presence of the required vials

STOPAttention: To avoid damaging the 2695D Dissolution Dispenser, use only pre-slit septa on the vials (see Appendix B, Spare Parts). Do not use low-volume inserts. Also, use only opaque vial caps to ensure that vial scanning operates properly.

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(in groups of 6 or 8) just before transfer. If a vial is missing from the carousel, an error is displayed on the 2695D screen.

• Whenever you run a dissolution test, press the Scan Vials screen key (see Figure 6-4) to prompt the 2695D software to scan for all required vials.

When you press the Scan Vials screen key, a progress bar (Figure 6-7) indicates the percentage of vial positions scanned. When vial scanning is complete, a report (Figure 6-8) is displayed that indicates the presence or absence of vials in the 2695D carousel.

If the vial scanning report indicates missing vials, open the 2695D sample compartment and place vials in the indicated carousel(s), then continue the test.

Figure 6-7 Vial Scanning Progress Bar

62%


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Figure 6-8 Vial Scanning Report Display

6.1.5 Applying Initial ConditionsThe Initial Conds (Initial Conditions) screen key in the Run Samples screen (Figure 6-3) applies the initial conditions for the first sample in a dissolution method.

Initial conditions are set for:

• Flow rate

• Composition

• Wavelength (if the system is controlling the Waters 486 or 2487 detector)

• Column temperature

• Sample chamber temperature

• Degasser mode

• Bath temperature (if you are using the Hanson SR8-Plus)

Note: You must press Initial Conds before you start a run, unless you enter the initial conditions for the run in the first row(s) of the dissolution method using the Equil or Condition function.

You can also set these parameters using the Status screen (see Section 6.2, Monitoring Dissolution System Status).

For more information on applying initial conditions, see the Waters 2695 Separations Module Operator’s Guide, Section 5.1.1, Running a Sample Set.

okokokokokok

okokokokokok

okokokok

MISSINGok

okokokokokok

1

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6.1.6 Printing Dissolution ReportsTo print the run-time parameters of your dissolution testing, in the 2695D Configuration screen (Figure 4-4):

1. Press Reports to enable reporting to a diskette or a connected printer.

2. Select Dissolution, then press OK.

During a dissolution test run, the 2695D generates a real-time report of events as they occur during your dissolution test. For more information on use of the 2695D disk drive, see the Waters 2695 Separations Module Operator’s Guide, Section 3.2, Configuring the Separations Module, or Section 6.5, Using the Disk Drive.

Figure 6-9 is an example of a dissolution test report showing the transfer of three samples (at 5, 10, 20 minutes) to vials 9-32 with a standard in vial 1. The output suggests that the “Collect all before LC” option was enabled in the dissolution method, since the three transfers appear without any intervening LC injections. The report page shown in Figure 6-9 includes only the standard and sample injections for the first (5-minute) sample. A complete report would include the injections for the 10- and 20-minute transfers.


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Figure 6-9 Example of a Dissolution Test Report

REPORT: Waters 2695D Separations Module

SERIAL NUMBER: G97SM4454M

PRINTED: 02/17/01 12:27:08pm

USER: User

CONFIGURATION: Syringe (250 uL), Loop (100 uL)

DISSOLUTION: 8 syringes, 2 baths, type (generic)

->Transferred to vials at 06/17/00 12:32:52pm(Bath A, 5.0 min, A9-A16)

->Transferred to vials at 06/17/00 12:37:54pm(Bath A, 10.0 min, A17-A24)

->Transferred to vials at 06/17/00 12:47:55pm(Bath A, 20.0 min, B25-B32)

->Standard injected at 06/17/00 12:48:15pm(20.0 uL from vial 1)

Inject 1 of 1, Line 2

->Sample injected at 06/17/00 01:19:32pm(20.0 uL from vial 9)


(Bath A, Vessel 1, at 5.0 min)
















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6.2 Monitoring Dissolution System Status

The 2695D Status screen displays the progress of a dissolution test and the status of the Waters Transfer Module and bath (Figure 6-10 and Figure 6-11) at any time during a run. For information on customizing the layout of the Status screen pages, see Section 6.2.2, Customizing the Status Screen Layout.

6.2.1 Using the Status ScreenTo access the Status screen, press the Menu/Status key in any screen of the 2695D. Press Menu/Status again to return to the previous screen.

If you are using a bath or bath(s) other than the Hanson SR8-Plus, the Status screen appears as shown in Figure 6-10. If you are using the SR8-Plus, the Status screen appears as shown in Figure 6-11.

Figure 6-10 Status Page for Alliance Dissolution System (Generic Bath)

Transfer Module Syringe and Valve Status

Information about the valves and syringes of the Transfer Module appears in the Transfer Module Syringes and Valves Status section of the Status screen (Figure 6-10):

• The active valve group (A, B, C, or D) is indicated by a filled-in circle. The inactive valves are indicated by empty circles.

• The current volume of each of the six or eight syringes is indicated to the right by a numeric value (mL) and a fill bar.

DissolutionDispenser and

Transfer ModuleStatus Section

Transfer ModuleSyringes and Valves

Status Pane

Monitoring Dissolution System Status 119

6

Dissolution Dispenser and Transfer Module Status

Status information about the Dissolution Dispenser and the Transfer Module appears in the Dissolution Dispenser and Transfer Module Status section of the Status screen (Figure 6-10).

• On the top line of the section is the status of the Dissolution Dispenser, for example “Waiting for aliquot” or “Running” (see Table 6-2 for a description of each status entry).

• The text to the right of the T icon (not shown in Figure 6-11) is the status of the Transfer Module. If the 2695D is initializing or unable to communicate with the Transfer Module, the T icon is grayed out. See Table 6-2 for the correlation between the 2695D and Transfer Module active states.

• The line below the T icon indicates the progress of the dissolution test, for example “Interval 1 of 6” (meaning, sampling interval 1 of 6 programmed).

• The field to the right of the T icon indicates the range of vials currently aligned under the Dissolution Dispenser needles (this vial range is represented by two numbers separated by a dash, to show the inclusive six- or eight-vial range).

Note: The vial range, which is not shown when the system is in certain states, is not shown in Figure 6-11.

• The box to the right of vial range indicates the number of minutes remaining until the next programmed dissolution sample time. The bath (A or B) corresponding to the next programmed sample time is also shown. Below the next programmed sample time is the last (final) programmed sample time and its bath.

When the Alliance Dissolution System is configured with Hanson SR8-Plus baths, the Dissolution Status pane displays two additional rows of bath status information (see Figure 6-11). The top row displays Bath A information; the bottom row displays Bath B information.

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Figure 6-11 Status Page for Alliance Dissolution System (Hanson SR8-Plus)

• The A and B boxes are grayed out when the 2695D is initializing or unable to communicate with one or the other bath. In the single-bath configuration, the B box is always grayed out.

• To the right of each bath box, in order, are the following fields:

– The “bath ID,” the name (up to 6 characters) assigned to the SR8-Plus. For information on setting the SR8-Plus bath ID, see the Hanson SR8-Plus Operational Manual.

– The temperature set point, editable when the test status is Idle (in °C).

– The current temperature of the bath (in °C).

– The paddle shaft speed, editable when the test status is Idle (in rpm). This field is used to both set and monitor shaft speed (shown OFF for Bath B in Figure 6-11).

– The elapsed test time, display only (in minutes).

Note: You can make changes only to fields that have a solid border.

Table 6-2 shows the active states of the 2695D and the Transfer Module as they occur during a test. See the discussion “Inactive States” below for information on other states that may be displayed on the Status screen. See the Waters 2695 Separations Module

Hanson

Bath StatusSR8-Plus


6 S t a t e s

Operator’s Guide, Section 4.3, Monitoring Your HPLC System, for more information on other Status screen fields.

Table 6-2 Di s s o l u t i o n D i s p e n s e r a n d T r a n s f e r M o d u l e A c t i v e

Dissolution Dispenser Status Transfer Module Status

Running – A test is in progress; anticipating the next sample time.

Selecting vials – There is less than 3 minutes until the next sample is ready to dispense. The appropriate vials are being aligned under the Dissolution Dispenser.

Waiting for aliquot – The required vials are aligned under the Dissolu-tion Dispenser ready to receive the pending samples.

Rinsing (optional) – If the dissolution method specifies a pre-sample rinse greater than 2.5 mL, then an explicit “rinsing” state occurs before the sample time point. Default is 7.5 mL. The fluidic path is directed toward waste or back to the vessels. (Recirculation is an option for single-bath systems only.)

Sampling – At the programmed time point, the final 2.5 mL of sample rinse volume is removed from the vessel and dispensed while the Dissolu-tion Dispenser needles are in the Up position. The fluidic path is directed toward waste or back to the vessels. (Recirculation is an option for single-bath systems only.)

Lowering dispenser – The Dissolu-tion Dispenser needles are lowered into the waiting vials after the Disso-lution Dispenser lines have been loaded with the sample taken at the programmed time point.

Measuring – While the Dissolution Dispenser needles are moving down, the Transfer Module syringes are filled from the vessels with the programmed sample volume that is later expelled into each vial.

Waiting – The Transfer Module is waiting for the needles to be in position below the vial septa.

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Inactive States

There are several inactive states for both the Dissolution Dispenser and the Transfer Module that may appear on the Status screen during a dissolution test.

• If the Transfer Module is not communicating with the 2695D, the T icon status reads Off-line. If it occurs during a test, an error message is logged.

• If the Transfer Module is communicating with the 2695D but is not active or no samples are scheduled for transfer, the T icon status reads Idle.

• If the Dissolution Dispenser encounters an error, the Dissolution Dispenser status reads Error. To clear the error, re-home the system using the Dissolution Diagnostics (see Section 8.2.2, Performing Dissolution Diagnostics, the “Homing the Dissolution System” discussion).

• If the Dissolution Dispenser is waiting for the Transfer Module to complete a sample transfer, the dissolution status reads Running until the operation of the Transfer Module and the Dissolution Dispenser is synchronized.

Dispensing – The needles are in the vials while the Transfer Module expels the measured sample volume.

Dispensing – The syringes are being emptied, effectively pushing the timed sample out of the tubing and into the vials.

Raising dispenser – The Dissolu-tion Dispenser needles are raised after the syringes are emptied.

Dispensed – The syringes have been emptied, but the needles are not yet fully raised.

Backflush – A backflush occurs when the disso-lution method does not specify “replace media.” A backflush is a syringe cycle that draws 2.5 mL from each vessel and returns the media to the same vessels to clear particulates from the filters.

Replacing (optional) – The Transfer Module is returning to the vessels the volume removed for this cycle (only when the dissolution method specifies “replace media”). The volume removed equals the sample volume plus the volume that went to waste during rinsing and sampling. In the single-bath configuration where the Dissolution Dispenser outlet tubing recirculates to the vessels, the replaced media volume is the sample volume only.

Washing (optional) – Fresh media is flushed through the C line, then out to waste.

Table 6-2 Dissolution Dispenser and Transfer Module Active States (Continued)

Dissolution Dispenser Status Transfer Module Status


6

Aborting Samples

If you monitor the dissolution test on the Status screen and you want to abort the test:

1. Press Abort Samples. If samples have already been transferred to the 2695D, a prompt to continue processing appears, as shown in Figure 6-12.

2. Press Yes to continue processing samples, or press No to stop processing.

Figure 6-12 Prompt to Continue HPLC Processing of Transferred Samples

You can press Stop Inject to suspend the injection. You then have the option to either abort or resume the injection. If you abort, you have the option to resume or abort samples.

For more information, see the Waters 2695 Separations Module Operator’s Guide, Section 5.1.5, Stopping a Run.

6.2.2 Customizing the Status Screen LayoutTo customize the layout of the Status screen pages:

1. From the Main screen, press Config, More, then Status Layout. The Status Page Layout dialog box is displayed (Figure 6-13).

Each line in the Status Page Layout dialog box consists of a selection box, the name of the system feature to be displayed, and the relative size of the feature. By using the Raise and Lower screen keys, you can specify the order in which the status of a feature is displayed.

124 Making a Run

6

The Status screen has a grid-like pattern of six blocks across and three blocks down. The measurements next to each item on the Status Page Layout dialog box specify the size of each item in relation to the full grid. The 2695D software attempts to fit all enabled features on the Status screen in the specified order. However, if you select all features, the system does not have enough room to display them all.

Figure 6-13 Status Page Layout Dialog Box

2. Using the 2695D Up/Down arrow keys, select an item on the Status Page Layout dialog box.

3. Press the Enable screen key to enable display of the item (the selection box is filled in). Press Disable to disable display of an item.

If an item is already enabled for your system configuration, the screen key reads Disable. If a feature is disabled, the screen key reads Enable. If the Enable key is grayed out, the item is not available in your configuration.

4. Press Raise to move an enabled feature higher in the order of display. Press Lower to move an enabled feature lower in the order of display.

Note: Press Reset Defaults to return to system defaults for the Status screen.

5. After you are satisfied with the enabled features and their display order, press Apply to save the changes.

6. Press Close to exit from the Status Page Layout dialog box.


7

Chapter 7Maintaining the Dissolution System

This chapter describes maintenance procedures you can perform on your Waters Alliance Dissolution System to ensure accurate and precise results.

7.1 Maintenance Considerations

Safety and Handling

When you perform maintenance procedures on your Alliance Dissolution System, keep the following safety considerations in mind.

STOPAttention: To avoid damaging electrical parts, never disconnect an electrical assembly while power is applied to the 2695D Separations Module. Once power is turned Off, wait approximately ten seconds before you disconnect an assembly.

STOPAttention: To prevent circuit damage due to static charges, do not touch integrated circuit chips or other components that do not specifically require manual adjustment.

Caution: To prevent injury, always observe good laboratory practices when you handle solvents, chemicals, and dissolution media, change tubing, or operate the Alliance Dissolution System. Know the physical and chemical properties of the dissolution media you use. Refer to the Material Safety Data Sheets for the solvents or media in use.

Caution: To prevent injury, do not attempt to access the inside of the Waters Transfer Module. The Waters Transfer Module contains no user-serviceable parts.See the Waters 2695 Separations Module Operator’s Guide and the operator’s guide for the detector in use for information concerning access to those instruments.

Maintenance Considerations 126

7

Proper Operating Procedures

You can help keep your Waters Alliance Dissolution System operating reliably by following the procedures and guidelines described in Chapter 5, Setting Up the Dissolution System, Chapter 6, Making a Run, and Appendix C, Solvent Considerations for a Dissolution System.

Spare Parts

Refer to Appendix B, Spare Parts, for spare parts information and for a list of the contents of the 2695 Startup Kit and the Waters Alliance Dissolution System Startup Kit. Parts not included in Appendix B are not recommended for replacement by the customer.

Contacting Waters Technical Service

If after performing the procedures in Section 7.2, Routine Maintenance Procedures, or in Section 7.2.1, Maintenance Schedule, you are unable to correct a problem, contact Waters Technical Service at 800-252-4752, U.S. and Canadian customers only. Other customers, call your local Waters subsidiary or your local Waters Technical Service Representative, or call Waters corporate headquarters in Milford, Massachusetts (U.S.A.) for assistance.

7.2 Routine Maintenance Procedures

This section covers maintenance of the dissolution components of the Alliance Dissolution System. For information on maintenance of the 2695 Separations Module, see the Waters 2695 Separations Module Operator’s Guide, Chapter 7, Maintenance.

Note: There is no user maintenance required for the 2695D Dissolution Dispenser. If, upon inspection, you find leaks from the 2695D Dissolution Dispenser, contact Waters Technical Support.

Note: Waters recommends that you flush the entire system with at least 15 mL of HPLC-grade water after each test or when the system will not be used for at least 24 hours.

Caution: To avoid electrical shock, do not open the 2695D or the Waters Transfer Module cover. Except for the syringes, the transfer module does not contain user-serviceable parts.

127 Maintaining the Dissolution System

7
7.2.1 Maintenance Schedule
Perform the routine maintenance procedures in Table 7-1 at the indicated frequencies.

7.2.2 Replacing Waters Transfer Module Syringes

The Waters Transfer Module contains no user-serviceable parts. However, if you discover leakage in one or more of the transfer module syringes or when air bubbles in the fluidic tubing affect performance of the system, you can replace a syringe (Figure 7-1) using the procedure described in this section.

STOPAttention: To prevent damage to internal seals, operate the 2695D Dissolution Dispenser and the Waters Transfer Module only after the system has been “wetted,” either through priming, washing, normal operation, or using the fill and dispense diagnostic.

STOPAttention: To prevent damage to the 2695D Dissolution Dispenser and to the Waters Transfer Module, run only aqueous solutions or organic solutions of no more than 10% methanol through the system fluidic lines.

Table 7-1 Routine Maintenance Procedures for the Waters Alliance Dissolution System

Procedure Frequency

Inspect transfer module syringes (Section 7.2.2)

Before each use. Replace once a year, at minimum.

Replace Uni-Probe filters (Section 7.2.4) Before each test

Wash the Waters Transfer Module with 15 mL (per line) of HPLC-grade water (Section 7.2.4)

After each test

Inspect the fluidics for leakage or damage (Section 7.2.4)

Once a day (minimum)

Clean the Waters Transfer Module (Section 7.2.4)

Once a day (minimum)

Clean the dissolution test bath (Section 7.2.4) Once a day (minimum)

STOPAttention: Before each dissolution test, inspect the Waters Transfer Module syringes for fluid leakage from above and below the plunger and outside the syringe assembly.

Routine Maintenance Procedures 128

7

Figure 7-1 Waters Transfer Module Syringe Assembly

Required Materials

• 1/4-inch flat-blade screwdriver

• Replacement syringe assembly, part number 700000222

To replace the transfer module syringe:

1. Use the 2695D Dissolution Diagnostics (see Section 8.2, User-Initiated Diagnostics) to prime the Transfer Module with 15 mL of HPLC-grade water.

2. Use the Fill diagnostic to fill Valve C with 1 mL of HPLC-grade water.

3. Use a flat-blade screwdriver to remove the shoulder screw of the syringe you want to replace (Figure 7-2).

STOPAttention: Before you perform this procedure, ensure that the Waters Transfer Module syringes are in the middle position by entering 1 mL in the Volume field of the Dissolution Diagnostics screen.

TP01556

Syringe Housing

Top of Syringe (Knurl)


7

Figure 7-2 Removing Transfer Module Shoulder Screw

4. Use your fingers to gently turn the knurl at the top of the syringe assembly counterclockwise until the barrel housing loosens from the assembly (Figure 7-3). Be sure to keep the syringe vertical during this procedure. To prevent cross-threading of the syringe barrel in the manifold, keep the syringe barrel straight (vertical) during the replacement procedure.

5. Ensure that the Teflon® gasket at the top of the syringe housing remains in place. If gasket replacement becomes necessary, remove all remnants of the old gasket, then install a new gasket (provided in the syringe assembly).

6. Remove and discard the used syringe.

7. Insert a replacement syringe assembly, then turn the knurl at the top of the assembly clockwise until the syringe assembly is finger-tight.

8. Reinstall the shoulder screw. To prevent leakage, do not overtighten the syringe.

TP01555

Shoulder Screw


7

Figure 7-3 Removing Transfer Module Syringe Housing

7.2.3 Replacing the Transfer Module FuseIf power to the Transfer Module becomes intermittent, or if you notice the front panel LED flashing, replace the fuse in the Waters Transfer Module.

Required Materials

• Flat-blade screwdriver, 1/4-in.

• Replacement fuse (TT-type fuse). Refer to the rating listing on the back panel of the instrument and Appendix B for the part number.

To replace the Transfer Module fuse:

1. Use the screwdriver to turn the fuse holder on the Transfer Module rear panel 1/2 turn to the left (Figure 7-4).

2. Gently pull out the fuse holder.

3. Discard the blown fuse and replace it with a properly rated fuse.

TP01553

Turn Knurled Knob atTop of Syringe Barrel

Housing Counterclockwise


7

Figure 7-4 Waters Transfer Module Rear Panel

7.2.4 Maintaining Other Parts of the Dissolution SystemOther maintenance procedures you must perform regularly are:

• Replacing the Uni-Probe filter

• Washing the transfer module

• Inspecting and replacing fluidic connections

• Cleaning the components

• Cleaning the dissolution bath

Replacing the Uni-Probe Filters

To ensure filter efficiency and to prevent interference from particles and solutions used in previous tests, replace the Uni-Probe inline filter on each Uni-Probe assembly before each dissolution test.

Required Materials

• Bidirectional 25-mm filters, 1-µm pore size

STOPAttention: For optimal system performance, use filters with bidirectional flow capability and a nominal pore size of not less than 1.0 µm (such as the Gelman #4523 Glass Fiber Acrodisk 1 µm x 25 mm filter).

COMM

1 2 3

CP

U F

UN

CT

ION

AUXILIARYI/O

TP01545

3A TT FUSE

Fuse


7

Procedure

To replace the filter:

1. Disconnect the Uni-Probe fluidic tubing connector from the filter.

2. Remove the used filter from the Uni-Probe and discard.

3. Insert the new filter onto the Uni-Probe check valve assembly as shown in Figure 7-5.

Figure 7-5 Replacing the Filter on the Uni-Probe

4. Reconnect the Uni-Probe assembly fluidic tubing connector to the corresponding transfer module fluidic line.

Washing the Transfer Module

Wash the Waters Transfer Module after each test with at least 15 mL of HPLC-grade water per fluidic line (or per valve). You can use the Uni-Probe wash station or any other appropriate vessel to hold the water and all the Uni-Probes (Figure 7-6).

Before you run another dissolution test, replace the filters on the Uni-Probes (see the discussion “Replacing the Uni-Probe Filters” above).

Note: During a wash cycle, when the source valve is A or B, an automatic backflush is performed.

To wash the dissolution system using the Uni-Probe wash station:

1. Fill the Uni-Probe wash station with HPLC-grade water up to 2 inches from the top of the wash station.

2. Detach each Uni-Probe from its vessel cover.

3. Insert each Uni-Probe into a hole in the Uni-Probe wash station cover.

TP01558


7

4. Ensure that the fluidic lines from Valve C of the transfer module are routed through the small holes in the Uni-Probe wash station and are immersed in the water or wash solution.

5. Ensure that the fluidic lines from Valve D are routed to waste, either directly or through the 2695D separations module.

6. From the 2695D Main screen, press the Menu/Status key to display the Status screen.

7. Press the Direct Functions screen key.

8. Select Set Up Transfer Module (normally number 7) from the Direct Functions menu (see Figure 5-3), then press OK. The Set Up Transfer Module dialog box is displayed (see Figure 5-4).

9. Enter a volume (per syringe) in the Volume field (minimum entry is 2.5 mL).

Figure 7-6 Washing the Dissolution System Using the Uni-Probe Wash Station

10. Press the Wash All screen key. The Wash All function automates the fill and dispense function for all four transfer module valves (C to D, A to D, B to D) with automatic backflushing between collections from Valves A and B.

Note: Valve B of the transfer module is not washed in a single-bath system.

TP01569

Connect Uni-Probes toWaters Transfer Module

HPLC-GradeWater

WashStation


7

The 2695D Status screen displays the status of the valves, syringes, and transfer module by displaying Idle, Washing, or Backflush during the corresponding phases of the Wash All function.

11. When the wash function is complete, remove the Uni-Probes from the Uni-Probe wash station (or other wash container), and return them to the appropriate dissolution vessels.

12. Reroute the Valve C fluidic lines from the transfer module to the media replace source(s).

Inspecting and Replacing Fluidic Connections

The Teflon® fluidic connections of the Alliance Dissolution System require inspection at least once a week. If you discover a leak, replace the fitting as directed in Section 3.2.1, Assembling Fluidic Connections. If you discover damage to the tubing, replace with tubing of the same diameter and length from the appropriate tubing kit (see Table B-1).

Cleaning the Waters Transfer Module

Clean the exterior of the Waters Transfer Module with a damp non-particulating cloth periodically. The frequency of cleaning depends on the amount of usage and the operating environment.

Cleaning the Dissolution Test Bath

For users of the Hanson SR-8 Plus Dissolution Test Station, see the cleaning procedures in the Hanson SR8-Plus Operational Manual. For users of other manufacturer’s baths, see the applicable operation and/or maintenance guide.


8

Chapter 8Error Messages, Diagnostics, and Troubleshooting

The Waters Alliance Dissolution System provides error message and startup and user-initiated diagnostics to troubleshoot problems with the 2695D and the Waters Transfer Module. See the appropriate operator’s guides for information about error messages, diagnostics, and troubleshooting the other instruments in your dissolution system.

8.1 Startup Diagnostics and Error Messages

8.1.1 Startup DiagnosticsStartup diagnostics are executed automatically when you power on the Waters 2695D Separations Module. See the Waters 2695 Separations Module Operator’s Guide, Chapter 3, Preparing the 2695 Separations Module for Operation, for information on the 2695D routine startup diagnostics.

The startup diagnostics include verifying the installation and proper positioning of the Dissolution Dispenser in the 2695D. If startup diagnostics are successful, the display shows a confirmation message.

If a startup diagnostic fails, an error message is generated. Table 8-1 shows the error messages and their possible causes and recommended remedies.

Table 8-1 Di s s o l u t i o n S y s t e m E r r o r M e s s a g e s

Error Message Possible Cause Recommended Action

[Dissolution method name] cannot be run on a 6- [an 8-] needle system.

The number of vessels specified in the the dissolu-tion method does not agree with the system configuration.

Change the number of vessels in the dissolution method editor, then save the edited dissolution method.

Startup Diagnostics and Error Messages 136

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[Dissolution method name] cannot be run on a system that [recirculates, does not recirculate] media back to the vessels.

The dissolution method does not agree with the system configuration with respect to recirculating media to the dissolution vessels. In a single-bath configuration, you have the option of directing the 2695D waste lines back to the dissolution vessels, minimizing media lost during a test.

Return to the 2695D Configuration screen and select Dissolution (see Figure 4-5), then select or deselect Recirculate media as appropriate for your system configuration. See also Figure 5-10.

[Dissolution method name] cannot be run on a two-bath system.

The dissolution method selected calls for media recirculation or rapid sampling. Both options run only on single-bath systems.

Change your configuration to a single-bath system, or deselect the media recircu-lation and/or rapid sampling option(s).

Bath speed out of tolerance This error is displayed and logged if the out-of-toler-ance alarm is enabled in the dissolution method and if the Hanson SR8-Plus reports an out-of-tolerance bath speed.

Check paddle speed, reset out-of-tolerance alarm, or consult Hanson SR8-Plus Operational Manual.

Bath temperature out of tolerance

This error is displayed and logged if the out-of-toler-ance alarm is enabled in the dissolution method and if the Hanson SR8-Plus reports an out-of-tolerance bath temperature.

Equilibrate bath, reset out-of-tolerance alarm, or consult Hanson SR8-Plus Operational Manual.

Bath temperature [A, B] is out of tolerance.

At the start of a test, the temperature of one or both baths (SR8-Plus only) is out of range (± 0.5 °C).

Equilibrate bath tempera-ture to the conditions specified in the dissolution method before beginning the test.

Bath [A, B] temperature is not ready (SR8-Plus only)

Bath not equilibrated to set point ± 0.5 °C

Equilibrate bath (see Hanson SR8-Plus Opera-tional Manual).

Table 8-1 Dissolution System Error Messages (Continued)


137 Error Messages, Diagnostics, and Troubleshooting

8

A selected dissolution method contains no sample time intervals.

One of the two dissolution methods selected for a dual-bath test contains no sample time intervals.

Recheck one or both disso-lution methods to be used in a dual-bath test.

An unknown device is communicating on the serial port.

The 2695D RS-232 communication port B is detecting unexpected data.

RS-232 communication port B is dedicated to operation of the Waters Transfer Module and the Hanson SR8-Plus bath(s). Be sure no other type of device is connected to port B or to any port on the Transfer Module or on the Hanson SR8-Plus.

Cannot start a dissolution test. Do you want to re-home the Dissolution Dispenser and Transfer Module?

The previous dissolution test ended in an error. A new test cannot begin without first clearing the error status.

Respond Yes to clear the status. This also ensures the Dissolution Dispenser and Transfer Module are in the home positions.

Could not home the dispenser.

The 2695D encountered an error when homing the 6- or 8-needle Dissolution Dispenser.

If the problem persists, contact Waters Technical Service.

Do you want to continue processing the sample set?

This prompt appears after you press Abort Samples on the Status screen if at least one sample transfer has already occurred.

Respond Yes if you want the 2695D to complete running HPLC injections from the vials already filled.

Do you want to regenerate the sample set with these parameters?

This prompt appears when you are editing a dissolution method if you make changes to one or more parameters in the Para-metric View or related dialog boxes that affect a previously generated row or rows.

Respond Yes to keep the Functional View consistent with the Parametric View. Respond No if you have customized generated rows in the Functional View that you do not want overridden by the Parametric View.




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Dissolution [reason] This error is displayed and logged when the dissolution test fails for one of the following reasons. The 2695D status that appears on the Status screen reads “Error”.• TM syringe – The Transfer Module syringe transport is

jammed.• TM sensor – The Transfer Module home position

sensor has failed.• Carousel – The required vials cannot be located under

the Dissolution Dispenser when needed.a

• Vial scan – An automatic pre-transfer scan has determined that one or more required vials is missing.a

• Couldn’t dispense – The Transfer Module failed to dispense the sample when requested to do so.

• Move dispenser – The Dissolution Dispenser (needles) failed to move up or down.

• Comm error – Lost communication during a dissolution test.b

• Couldn’t continue – The Transfer Module failed to perform the post-sample backflush or media replacement.

• Missed pill drop – The prompt to drop dosage forms in Bath B was not acknowledged within 30 seconds.

Dissolution Dispenser move failed

The 2695D encountered an error while trying to move the Dissolution Dispenser.

If the problem persists, contact Waters Technical Service.

Error downloading dissolu-tion test parameters

The system encountered an error while setting initial conditions for a test.

Check the system configu-ration (bath type and number of baths) and the RS-232 serial communica-tion cabling.

Error identifying system configuration

When scanning for dissolu-tion instruments, the system encountered a discrepancy between configuration parameters and detected devices.

Ensure you have selected the correct bath type (SR8-Plus or Generic) and number of baths, then scan again.




8

Error setting initial temperature

When setting initial condi-tions before performing a dissolution test, the 2695D cannot set the bath temper-ature of a Hanson SR8-Plus.

Check the system configu-ration and communications connections, then try again.

Found differences between the instructions of the Para-metric View and the entries in the table. The first of these is on line [n].

When paging through the views of the dissolution method editor, the 2695D found that the Functional View differs from the Para-metric View parameters. This may indicate a custom-ization you have made to the Functional View.

Make sure you understand the sources of these differ-ences. If not a legitimate customization, change the Functional View to match the entries in the Parametric View and associated dialog boxes.

Missed a dissolution sample

This error is displayed and logged when the Transfer Module is unable to deliver a collected sample to the 2695D. The dissolution test fails.

Recheck fluidic connec-tions and Transfer Module syringes.

Please make sure that sample times are at least [n] minutes apart in the method selected for [Bath ID].

When starting a test using both baths of a dual-bath configuration, the system found that the sample times in one of the specified methods specified were not far enough apart to allow for the programmed rinse between samples.

Recheck sample timing.




8

Please use a smaller rinse volume, or an initial sample time no less than [n] minutes.Please use a smaller rinse volume, or schedule no two samples less than [n] minutes apart.Please use a smaller rinse volume, or set the infinity test OFF or greater than [n] minutes.

When editing a dissolution method, the system found that the selected rinse volume is too large to be completed:(a) Between the start of the test and the initial sample time(b) Between adjacent sample transfers; or (c) Between the final sample transfer time and the infinity test transfer

Perform the requested action.

Removal of vials or carou-sels during a dissolution test may invalidate the results.

This message appears whenever you open the sample compartment door during a dissolution test.

Press OK to access the carousel selection (Door is Open) screen, or close the door to clear the message.

Sample vial conflict The requested vial ranges in a dual bath test setup at least partially overlap.

Adjust the vial selection for one or both baths.

The dissolution method cannot be run, because dissolution is not supported by the hardware.

This error occurs if you attempt to run a dissolution method on a system that is unable to initialize the Dissolution Dispenser on startup.

Recheck your configuration.

Contact Waters Technical Service.

The dissolution method cannot be run, because there is no dissolution bath available.

When configured for use with the Hanson SR8-Plus, the system encounters this error when you try to run a dissolution method when the bath is off-line.

Recheck communication connections and check that bath(s) and Transfer Module are powered on.

The minimum interval between adjacent samples is 2.0 minutes.

You have made entries in the sample timing table that are less than 2.0 minutes apart.

Samples must be timed to be drawn a minimum of 2.0 minutes apart. Adjust your sample timing table and try again.




8

8.1.2 Error LogThe Error Log records system error messages (whether dissolution specific or not). From the 2695D Main screen, press the Log screen key to display the Error Log (see the Waters 2695 Separations Module Operator’s Guide, Section 8.2, Using the Error Log).

8.2 User-Initiated Diagnostics

If you encounter problems during operation of the Alliance Dissolution System, you can troubleshoot the system by selecting the diagnostic routines described in this section.

The number of sample vials for this run exceeds the capacity of the carousels.

Based on the number of needles in your Dissolution Dispenser (6 or 8), the number of entries in your sample timing table, the inclusion of an infinity test, and the selected sample vial range, the 120-vial capacity of the 2695D is exceeded.

Choose a lower sample vial range, or reduce the number of sample times.

The Sample Timing list is empty.

When you try to save a dissolution method, the 2695D software finds that the method has no sample timing list.

Fill out the sample timing list and try again.

The selected offset is not practical for these methods. An offset of [n] minutes is recommended.

When beginning a test using both baths in a dual-bath system, the system has determined that the delayed offset for the start of samples from the second bath is not enough to prevent sample timing conflicts.

Enter the recommended offset in the delayed start field.

a. You can replace the missing vial(s) or carousel(s) and resume the test with the error cleared when you close the sample compartment door, depending on the timing of your dissolution sample transfer.

b. If corrected within a certain amount of time (determined by test conditions), the test may resume automatically.



User-Initiated Diagnostics 142

8

For information on user-initiated diagnostics for other (non-dissolution) functions of the 2695D Separations Module, see the Waters 2695 Separations Module Operator’s Guide, Section 8.3, Performing Main Diagnostics, and Section 8.4, Performing Other Diagnostics.

Contacting Waters Technical Service

If you are unable to correct an error condition after running the user-initiated diagnostics and troubleshooting the system, contact Waters Technical Service at 800-252-4752, U.S. and Canadian customers only. Other customers, call your local Waters subsidiary or your local Waters Technical Service Representative, or call Waters corporate headquarters in Milford, Massachusetts (U.S.A.) for assistance.

Note: Only qualified Waters service personnel can access service diagnostics.

8.2.1 Accessing the User-Initiated DiagnosticsThe dissolution software diagnostics help you correct problems with:

• Homing the Dissolution Dispenser

• Moving the Dissolution Dispenser

• Homing the Transfer Module syringes

• Priming the Transfer Module

• Filling the Transfer Module syringes with specific volumes

• Dispensing specific volumes through the Dissolution Dispenser to waste or to specified vials

You perform user-initiated diagnostics from the Diagnostics screen (Figure 8-1), which you access from the 2695D Main screen by pressing the Diag screen key.


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Figure 8-1 Diagnostics Screen

In the Transfer Module pane on the first Diagnostics screen are two fields:

• Discharge cycles – The number of times the syringes in the transfer module are emptied.

• Protocols – The number of dissolution tests completed (for all baths connected to the system).

8.2.2 Performing Dissolution DiagnosticsYou perform dissolution diagnostics from the Dissolution Diagnostics screen (Figure 8-2). The Dissolution Diagnostics screen also displays the status of the:

• Dissolution Dispenser

• Transfer Module

• Transfer Module valves

• Syringes

• Vials

These fields change as you perform the dissolution diagnostics.


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Figure 8-2 Dissolution Diagnostics Screen

Homing the Dissolution System

The Dissolution Dispenser homes automatically during the 2695D startup diagnostics. To return the Dissolution Dispenser to the home (top) position at any time:

1. In the Diagnostics screen, press the Other Tests screen key, select Dissolution from the Other Diagnostics scroll box, then press OK. The Dissolution Diagnostics screen is displayed.

2. From the Dispenser drop-down list, select Top (home), then press the Home screen key.

A standby message on the 2695D screen indicates the software is homing the Dissolution Dispenser. When the Dissolution Dispenser is in the home position, the Dispenser status indicator is on (filled in).

Note: Performing this diagnostic also homes the Transfer Module.

Moving the Dissolution Dispenser

Note: When the Dissolution Dispenser is in the bottom position, you cannot move the carousel manually.

To move the Dissolution Dispenser to the middle or bottom position manually:

1. Access the Dissolution Diagnostics screen (see step 1 above).

2. Move to the Dispenser drop-down list.

3. To move the Dissolution Dispenser to the:

Transfer Module Status

TM Valve Status

Indicators

VialLocation

Dissolution Dispenser

Status

Syringe Volume Indicator

Dispenser Home Sensor Indicator


8

• Middle position, select Middle, then press Enter.

• Bottom position, select Bottom, then press Enter.

Note: You can move the Dissolution Dispenser to the Bottom position only when you have selected a vial range in the Destination field on the Dissolution Diagnostics screen and when a carousel is present in the 2695D carrier. When you select Bottom, the diagnostic moves the dispenser down and positions the needles over the selected vials in the carousel.

Note: When the Dissolution Dispenser is in either the Middle or the Bottom position, the Dispenser status indicator is off (not filled in).

8.2.3 Performing Transfer Module Diagnostics

Homing the Transfer Module

The Waters Transfer Module homes automatically when you power on the instrument. To home the transfer module at any other time:

1. Access the Dissolution Diagnostics screen.

2. Press the Home screen key. A standby message on the 2695D screen indicates the software is homing the transfer module.

Note: Performing this diagnostic also homes the Dissolution Dispenser.

Priming the Transfer Module

You can use the Dissolution Diagnostics to prime individual Transfer Module syringes and valves, either before making a run or after encountering air bubbles or other fluidics problems. See also Section 5.2.2, Setting Up the Waters Transfer Module.

To flush the system fluidics fully, use the procedure provided in Section 7.2.4, Maintaining Other Parts of the Dissolution System, the “Washing the Transfer Module” discussion.

To prime the transfer module syringes:


2. Move to the Source drop-down list.

3. To prime the fluidic tubing between:

• Bath A and waste, select (A) Bath A, then press Enter.

• Bath B and waste, select (B) Bath B, then press Enter.

• The wash or media replace vessels and waste, select (C) Wash/Replace, then press Enter.

4. Move to the Destination drop-down list.


8

5. Select Waste as the destination for the priming fluid, then press Enter.

6. Move to the Volume field.

7. Select the volume of priming fluid to use. The allowed range is 0.10 to 999.99 mL.

Using the Fill and Dispense Diagnostics

You can use the Fill and Dispense Diagnostics to manually fill the transfer module syringes with a specific volume, then dispense the same volume to sample vials (up to 1.5 mL) or to waste (up to 2.5 mL). To use the Fill and Dispense diagnostics:


2. Move to the Source drop-down list.

3. Select the source [(A) Bath A, (B) Bath B, or (C) Wash/Replace] of the fluid with which to fill the syringes. The available source selections may vary from those indicated if you are using a Hanson SR8-Plus and have assigned other names to the source bath(s).

4. Move to the Destination drop-down list.

5. Select the destination for the dispensed volume. The destination selections include vial ranges consistent with the configured number of needles/syringes in the system.

6. Move to the Volume field, then enter the volume to be dispensed. The allowed range is 0.10 to 2.5 mL.

7. Press the Fill screen key. The Transfer Module valve status indicators (see Figure 8-2) indicate the condition of the source valve (filled in = active). The syringe volume indicator displays the specified volume.

8. Press the Dispense screen key to dispense the specified volume to the selected destination.

8.3 Troubleshooting

8.3.1 Contacting WatersMost problems are relatively easy to correct. If you are unable to correct a problem or a failed condition, contact Waters Technical Service at 800-252-4752, U.S. and Canadian customers only. Other customers, call your local Waters subsidiary or your local Waters Technical Service Representative, or call Waters corporate headquarters in Milford, Massachusetts (U.S.A.) for assistance.


8

To expedite your request for service or technical support, have the following information available when you call Waters Technical Service:

• System configuration

• Dissolution System equipment serial numbers (including Waters 2695D) and the number of needles

• Waters Transfer Module serial number and number of syringes

• Dissolution bath vendor and model number

• Detector model and operating wavelength(s)

• Problem symptom(s)

• Flow rate

• Type of column

• Operating pressure

• Solvent(s)

Diagnostics

The dissolution system software can perform user-initiated diagnostics to help you troubleshoot basic system problems. For information on using the user-initiated diagnostics, see Section 8.2.1, Accessing the User-Initiated Diagnostics.

Error messages that may appear when you start up the Dissolution System and suggested corrective actions are described in Table 8-1.

8.3.2 Hardware Troubleshooting

This section covers information on troubleshooting problems specific to the Waters 2695D Separations Module and the Waters Transfer Module (Table 8-2). For information on troubleshooting the 2695D Separations Module for nondissolution-specific problems, see the Waters 2695 Separations Module Operator’s Guide, Section 8.5, Troubleshooting. For

STOPAttention: To avoid problems caused by power surges, line spikes, and/or transient energy fluctuations, use a power source that is properly grounded and free from variances.

STOPAttention: Use only solvents and other fluids compatible with your dissolution media when you operate the Alliance Dissolution System.

Troubleshooting 148

8

information on troubleshooting the Hanson SR8-Plus, see the Hanson SR8-Plus Operational Manual.

Table 8-2 General Equipment Troubleshooting

Symptom Possible Cause Corrective Action

Waters 2695D does not recognize 2487 or 486 detector in the Configuration screen

Detector not powered on. Power on the detector.

Incorrect IEEE-488 address Set the correct IEEE-488 address.

Faulty IEEE-488 cable connections, or faulty cable

Check IEEE address.

Check cable connections.

Replace cable.

2695D keypad not functioning

On board CPU busy

On board CPU locked up

Defective keypad

Wait for commands to be processed.

Recycle power to the 2695D.

Recycle power to the entire dissolu-tion system.

Run 2695D keypad diagnostic.Contact Waters Technical Service.

2695D startup diag-nostics do not recognize Dissolution Dispenser

Dissolution Dispenser not correctly installed.

Sensor diagnostics working incorrectly.

Recycle power to 2695D Separa-tions Module.


2695D Status screen indicates Waters Transfer Module not connected

Power to transfer module not on.

RS-232 cable from 2695D to transfer module not connected or connected incorrectly.

Low or dead battery on transfer module CPU board.

Check power.

Check cable connections.

Recycle power to system.



8
8.3.3 General Chromatography TroubleshootingFor information on troubleshooting your chromatographic system, see the Waters 2695 Separations Module Operator’s Guide, Section 8.5, Troubleshooting.
Waters Transfer Module fluid leakage from syringe assembly or housing

Incorrectly installed syringe

Loose or broken syringe

Worn syringe gasketValve leakage

Checks each syringe for leakage.

Tighten shoulder screw at bottom and knurl at top of syringe.

If leaking continues, replace syringe(s) and gasket.

Call Waters Technical Service.

Waters Transfer Module fluid leakage from fluidic connec-tions or drip tray

Fittings not tight.

Drip tray not draining correctly.

Tighten fittings.

Check tubing from the drip tray to waste reservoir.

If problem continues, contact Waters Technical Service.

Table 8-2 General Equipment Troubleshooting (Continued)

Symptom Possible Cause Corrective Action

Troubleshooting 150

Dissolution System Specifications 151

AAppendix ADissolution System Specifications

Table A-1 contains the specifications for the Waters® Transfer Module and the Waters 2695D Separations Module.

Table A-1 Alliance Dissolution System Operational Specifications

Condition Specification


Volume

Syringe Delivery Volume 0.1 to 2.5 mL

Sample Delivery Volume 0.8 to 1.5 mL

Sample Delivery Volume Accuracy ±20 µL (2% at 1 mL)

Speed

Collect, 2.5 mL 15 sec

Dispense, 2.5 mL 15 sec

Sample transfer timea

a. This requirement applies to protocols with optimized wash cycles.

2.0 min

Carryoverb

b. Single bath, 7.5 mL wash

<0.5% max

Physical Specifications

Size 11.25 in. (width) × 14.25 in. (height) × 19.25 in. (depth)(28.58 cm × 36.20 cm × 48.90 cm)

Weight 34.0 pounds (15.42 kg)

Electrical Specifications

Input Voltage 100 to 240 Vac, 50/60 Hz

Power 50 W


See the Waters 2695 Separations Module Operator’s Guide, Appendix A, Specifications.

B

Appendix BSpare Parts

Table B-1 lists Alliance® Dissolution System spare parts that are user-replaceable. Contact your Waters Technical Support representative for more information on spare parts for the Alliance Dissolution System.

Table B-1 Waters Alliance Dissolution System Spare Parts List

Part Number Item

430000131 Tubing Kit, 30-in. (single bath), 8

430000130 Tubing Kit, 60-in. (dual bath), 8

430271880 Tubing, 36-in. (inlet or waste), 8

725000122 Universal Uni-Probe Kit, pack of eight

725000123 Universal Uni-Probe Kit, pack of six

725000124 Uni-Probe Kit (VanKel), pack of eight

725000125 Uni-Probe Kit (VanKel), pack of six

700000242 Universal Uni-Probe, single (spare)

700000243 Universal Uni-Probe cover

700000244 Uni-Probe cover (VanKel)

700000245 Uni-Probe plug, adapter knob

700000246 Uni-Probe female adapter

700000247 Uni-Probe male adapter

700000263 Uni-Probe check valve, pack of forty eight

700000248 Uni-Probe O-ring

WAT200818 Gelman glass filter, 25 mm, 1-µm pore size

WAT046-10 Compression screw, 1/8-in.

WAT046-01 Ferrule, 1/8-in.

WAT025964 Compression screw, 1/16-in.

WAT077058 Ferrule, 1/16-in.

186000307 Screw-neck vial 12 × 32 mm with bonded pre-slit PTFE or silicone septa

Spare Parts 152

B

700000257 Fuse 3.0 A TT, rear panel

700000197 Fittings Kit, 8 fittings, 8 unions, 10 ferrules

700000200 Tubing Kit

700000212 2.5 mL syringe

71500034302 Waters Alliance Dissolution System Oper-ator’s Guide

71500269502 Waters 2695 Separations Module Oper-ator’s Guide

Table B-1 Waters Alliance Dissolution System Spare Parts List (Continued)

Part Number Item

153 Spare Parts

Solvent Considerations for a Dissolution System 154

C

Appendix CSolvent Considerations for a Dissolution System

This appendix provides information about solvents used in most dissolution systems.

Use the Alliance Dissolution System equipment with typical dissolution media as described in U.S. Pharmacopoeia (USP) official monographs.

Buffered Solutions

When using a buffer, use a good quality reagent and filter it through a 0.45-µm filter.

Do not leave the buffer stored in the system after use. Flush all fluidic pathways with HPLC-quality water before shutting the system down. Leave distilled water in the system or flush with 90 percent HPLC-quality water:10 percent methanol for shutdowns scheduled to be more than one day. Use a minimum of 45 mL of flushing solution for the Waters 2695D Separations Module and its associated dissolution system equipment.

Additional Solvent Information

For more information about solvents used in the Alliance Dissolution System, see the Waters 2695 Separations Module Operator’s Guide, Appendix C, Solvent Considerations.

Caution: To avoid chemical hazards, always observe safe laboratory practices when operating your system


I NDEX

Numerics2695D

access attention 42as the system controller 75column heater 31configuration parameters 71description 27dimensions 47diskette drive 28dissolution dispenser 25, 29dissolution methods 28HPLC analysis 26operator interface 27stand-alone mode 40system controller 40

AAlliance Dissolution System. See Dissolution

systemAutomatic rinse 33, 97AutoStartPLUS 82, 89

BBackflush 33Bath. See Dissolution bathBench space 42Buffered solutions, using 154busSAT/IN module 77

CChromatography, troubleshooting 150Cleaning the transfer module 135Column heater 31Column switching valves 31

Compression screw 56Configuring

components 67dissolution system 67

Connectionsfluidic. See Fluidic connectionspower. See Power connections

Conventions, documentation 22Custom serial cable 79

DDesktop power supply 49Detectors

control by Millennium³² software 70location 43setting up 88Waters 25, 33with busSAT/IN module 77

Diagnosticsdissolution system 149fill and dispense 87, 147startup 136user-initiated 142

Dimensions, transfer module 49Dispenser. See Dissolution dispenserDissolution bath

apparatus 24description 34dual 25, 39equilibrating 88fluidic connections 54, 58, 59fluidic path 55fuse requirements 44installation 42monitoring status 119non-SR8-Plus 77paddle speed 38parameters 75

Index

155 Index

INDEX

power connections 52powering on 82setting up to test 87signal connections 68, 77, 79single 25temperature 38, 137testing 25troubleshooting 136vessels 53, 61, 73

Dissolution dispenserdescription 25, 27eight-needle 25, 27function 29homing 30, 82, 138, 145moving 139, 145needle positions 30six-needle 25, 27

Dissolution methodscreating 89editing 99printing 109reviewing 99running 107

Dissolution reports 117Dissolution system

automatic rinse 33backflush 33components 25configurations 67description 25detectors 25, 33diagnostics 81, 142, 149dispenser 29dual-bath 25, 39, 59error messages 136features 25fluidic connections 54, 56fuses 43initial startup 81maintenance 126

I

methods 28, 38, 89, 99options 83power connections 45powering on 81required equipment layout 25setting up test bath 87single-bath 25, 58site selection 41spare partsspecifications 151status monitoring 119testing 81troubleshooting 147tubing 54unpacking and inspecting 44wash station 85, 133

Dissolution testingmulti-point testing 24overview 24single-point testing 24

Documentation conventions 22Dual-bath system

description 25fluidic connections 59, 62functional view 39

EElectric sampling probes 36

connecting 66Electrical connections. See Power

connectionsEquilibration, dissolution bath 88Equipment layout 25Error log 142Error messages

homing 82list 136

FFeatures

Index 156

INDEX

2695D Separations Module 27Alliance Dissolution System 25Waters Transfer Module 31

Ferrule. See FittingsFilters

Uni-Probe 66, 132use of 34

Fittings, connecting 56, 135Fluidic connections

Alliance Dissolution System 54assembling 56chromatography 54dual-bath 59, 62dual-bath system 25from transfer module to bath 60overview 54recirculation 66replacing 135single-bath 58, 61transfer module 60Uni-Probe 63

Fluidics, functional viewdual-bath 39single-bath 38, 55

Fuses, transfer module 43, 131

HHanson SR8-Plus

RS-232 connections 79troubleshooting 148use of in system 25

Hardware, troubleshooting 148Homing

dissolution dispenser 82, 138, 145during startup 82syringes 138transfer module 146

IIEEE-488 connections 69

157 Index

I

Infinity test 94Initial conditions, applying 116Injection view 99Inspecting. See Unpacking Alliance

Dissolution SystemInstallation

bath 42materials 42overview 41setup 42

Interface, operating 32

KKeys

computer 23instrument 23

LLabels screen key 91Loading view 99

MMaintenance

of fluidic connections 135procedures 126routine 128schedule 128spare parts 127

Media replacement 91Method icons

dissolution method 108sample set 108separation method 108

Methodsdevelopment 38, 89dissolution method editor views 99editing 99, 108icons 108

INDEX

I

programming 28Millennium³² software

connections 76control of detector 70setting up 89

Miscellaneous options, parameters 96, 97Multi-point testing 24

OOperating principles 37Operator interface 27Options

checking 83miscellaneous 97

Overviewdissolution method 99dissolution testing 24dual-bath fluidics 39fluidic connections 54of a run 99single-bath fluidics 38

PPaddle speed

for SR8-Plus 38infinity test 94setting 88

Parametersdissolution method 99miscellaneous options 97sample timing 93, 94separation condition 95

Parametric viewdescription 99dissolution parameters 99fields 91

PerformancePLUS degasser 31Pooling samples 93, 103, 104Post-sample wash

wash volume 97

Power connectionsdesktop power supply 49dissolution bath 42system 45transfer module 49, 52

Power supply. See Desktop power supplyPowering on

detectors 82dissolution bath 82dissolution system instruments 81

Pre-slit septa 25, 29, 83, 84, 114Priming

transfer module 33, 85, 146using wash station 85

Printingauto print interval 96connected to Hanson SR8-Plus 97dissolution method requirements 109reports 117run-time parameters 117

Probes 36

RRapid sampling 98Rear panel, transfer module

fluidic connections 60power connections 50, 51, 52

Recirculationfluidic connections 66of media 63

Related documentation 20Replacing

filters 132transfer module fuse 131

Reportsenabling 117printing 117

Required equipment layout 25RS-232 connections. See Signal

connectionsRun Samples screen key 107Running samples 107

Index 158

INDEX

SSafety considerations 126Sample set 38, 108Samples

pooling 93, 103Run Samples screen key 107running 107timing parameters 93, 94vials 32, 84, 103volume 91

Sampling interval 38Scan vials function 73, 114Separation conditions

definition 94parameters 95

Separation method 26, 95Separations module. See 2695DSepta, pre-slit 25, 29, 83, 84, 114Serial port connections. See Signal

connectionsService, Waters 127, 143, 148Setting

bath temperature 137miscellaneous options 96pooled sample parameters 104sample timing parameters 93separation condition parameters 95transfer module volume 92

Signal connectionsbusSAT/IN module 77dissolution bath 79IEEE-488 69Millennium³² data system 76non-SR8-Plus 77RS-232 78serial port 78SR8-Plus 79transfer module 79

Single-bath systemdescription 25fluidic connections 58, 61

159 Index

I

fluidics 38Single-point testing 24Site selection 41Solvent considerations 154Spare parts 152Specifications 151Starting up the system 81Startup diagnostics 136Status screen

display 86, 113function 110, 119page layout 124

Syringeshoming 138, 146leakage 128numbering 32speed setting 97transfer module 25volume 87

TTechnical service 127, 143temperature 31Temperature, bath 38Test results

accurate 34affected by tubing changes 61

Test station. See Dissolution bathTesting

multi-point 24preparing for 81setting up bath 87single-point 24

Transfer modulecleaning 135desktop power supply 49features 31fluidic connections 60fuse 131location 42power connections 49, 52

INDEX

I

priming 33, 85, 146signal connections 79syringes 25, 146troubleshooting 131, 150valve connections 61washing 133

Troubleshootingchromatography 150dissolution bath 136dissolution system 147hardware 148transfer module 150

Tubing 54, 61

UUni-Probe

description 34, 63filters 66fluidic connections 63operation 34replacing the filter 132use of 25wash station 85, 133, 134

Universal sampling probe 25, 34Unpacking Alliance Dissolution System 44User-initiated diagnostics 142USP out-of-tolerance alarm 97, 137

VValves, fluidic path 61Vials

loading 84ranges 99sample 32, 84, 103scanning 73, 114septa 25, 29, 83, 84, 114, 122

Viewsfunctional 99injection 99loading 99

parametric 99Volume

automatic rinse 97changes 34changes in tubing 61injection 88, 95media replace 91pooled samples 93priming 87rapid sampling 98syringes 87transfer module 92

WWash All function 133, 134Wash station 85, 133Waters detectors 25Waters Technical Service 127, 143, 148Waters Transfer Module. See Transfer

moduleWetted materials, use of 26

Index 160

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