bettersize solutions for pharmaceutical development-201912 ... · and the appropriate methodology...

Pharmaceutical SolutionsDevelopment, Manufacturing and Quality Control

BETTER PARTICLE SIZE SOLUTIONS

PA R T I C L E S I Z E

P O W D E R C H A R A C T E R I S T I C S

PA R T I C L E S H A P E

Particle Size Distribution of API and Excipients

A pharmaceutical dose or tablet contains the active pharmaceutical ingredient (API) which is the appropriate drug substance itself and excipients The API is commonly used in pharmaceutical manufacturing as it is the active pharmaceutical substance which is used in disease diagnosis, treatment, symptom relief and prevention. The particle size of the API is thus one of the most important aspects to be investigated in the formulation of a new drug and in the quality control of existing drugs. As thus, Particle size reduction and increment technologies as well as particle size measurement systems are routinely used to create, monitor and maintain optimal sizes of API for the benefit of the patient.

Although laser diffraction analysis has been recommended in ISO13320 and USP<429> as a particle size measurement method, for a specific API, there are still questions worth considering: the choice between dry and wet dispersion; how to disperse agglomerated pharmaceutical particles without breaking them and the appropriate methodology (SOP creation) for particle size measurement. The Bettersizer 2600 laser particle size analyzer can answer all these questions easily and confidently.

CCD camera

BETTERSIZER 2600

Sample D10 (μm) D50 (μm) D90 (μm)

Domperidone-1 1.74 9.36 22.91

Domperidone-2 1.75 9.34 23.00

Domperidone-3 1.72 9.28 22.94

Domperidone-4 1.71 9.28 22.93

Domperidone-5 1.74 9.34 22.95

Domperidone-6 1.72 9.31 22.94

Repearability 0.86% 0.35% 0.13%

ESSENTIAL ADVANTAGES

• Conforms with ISO13320: 2009 and USP<429>;

• Rigorous IQ/OQ certification process;

• Comprehensive R&D and validation capabilities;

• Meets the data security requirements (FDA 21 CFR PART 11) required for audit trails;

• Dispersion: Capable of Wet and/or Dry.

BETTERSIZER 2600 MEASURED DOMPERIDONE SAMPLE

www.bettersizeinstruments.com

Domperidone

Particle size (μm)

Bettersize Solutions for Pharmaceutical Development, Manufacturing and Quality Control

Measuring principle Laser diffraction, Fourier and Reverse Fourier optical system

Analysis theory Mie or Fraunhofer

Applications suspensions, emulsions, dry powders

Measuring range Wet: 0.02 - 2600 μm; Dry: 0.1 - 2600 μm

Number of size classes >100

Typical measurement time <10 seconds

Accuracy error / Repeatability error Wet: <0.5% / <0.5% ; Dry: <1.0% / <1.0% (GBRM D50)

Circulation / Dispersion / VolumeWet: Centrifugal pump / Ultrasound (50 W) / 600 ml

Dry: Venturi system, 0 - 5 bar

Laser: number / type / wavelength / power / class 1 / Fiber laser / 635 nm (red) / 3 mW / Class 1

Effective focal length 223 mm

Detector system Log-space arrangement

Detector channels / Angle range 92 (forward, lateral, and backward) / 0.016° - 165°

Conformity 21 CFR Part 11, ISO 13320, USP<429>, CE

Data export Excel, PDF, Word, JPG, etc.

Dimensions / Weight 705 x 318 x 295 mm (L x W x H) / 23 kg

Recommended operating system Windows 7 or higher, Intel Core i5, 4 GB RAM, USB 2.0

Wet dispersion and circulation system

Dry dispersion and circulation system

• New patented technology: Fourier and Reverse Fourier optical system

Bettersizer 2600 is characterized in particular by its unique and innovative optical bench design: the light focused on the de tectors through the lens is scattered by particles and detected in forward and lateral directions (reverse Fourier optics). In contrast to conventional laser diffraction devices, the backscattered light passes through the lens a second time. In addition, the cuvette is positioned at an angle of 35° to the incoming laser light.

This smart setup allows, on the one hand, the detection of stray light in a very wide angular range from 0.016° to 165°. On the other hand, in contrast to a pure Reverse Fourier structure, the particles do not have to lie in one plane – the simultaneous accurate measurement of both small and large particles is thereby achieved. • Automatic circulation, dispersion and measurement

Integrated with ultrasonic disperser, centrifugal circulating pump, automatic water intake, drainage and spill-proof system, Bettersizer 2600 is suitable for a wide range of samples and can fully disperse them to provide results with high accuracy and repeatability.

FEATURES AND BENEFITS

SPECIFICATION



Particle Shape and Size Analysis for API and Excipients

Visualises uniform disintegration by imaging

Visualises partial disintegration by imaging

Multilayer structureBeVision S1 analysis API and excipients

(a) (b)

BEVISION S1

The particle size of API and excipients has a great influence on the quality of the drug and its formulation process. As a relatively mature technology, laser diffraction is widely used in particle size measurement for API and pharmaceutical excipients because of its advantages, such as fast detection and high repeatability.

There are however other issues which need to be addressed, the particle size of the final product cannot be visually confirmed and you do not know if the sample is in an agglomerated state or broken. As well as this, for many formulations, the shapes of the raw and auxiliary crystals are also critical, in the case of many pharmaceuticals, they are crystalline and are generally rod-shaped, or aggregated? In addition to the wealth of information provided by laser diffraction, the capabilities of the image particle size and shape analyzer BeVision S1 provide the answers the formulator needs.


• Cross-validation of different methodologies for particle shape and size measurement of API and excipients;

• Check crystal morphology and agglomeration state of API and excipients;

• Quantify a variety of particle parameters and distributions, including particle size, L/D ratio, circularity, area, etc;

• Automated image processing and analysis, including threshold setting, separation, filling and extraction, fast and easy to operate.

BEVISION S1 ANALYSIS OF API AND EXCIPIENTS



Measuring range 1 - 3000 μm Scale accuracy 10 μm

Max magnification 4000 times Automatic split speed <1 second

Repeatability error ≤3.0% (GBRM D50) Split success rate >93%

Accuracy error ≤3.0% (GBRM D50) Operating system Windows 7 or higher

CCD camera 5 million pixels Interface USB 2.0 or USB 3.0

MicroscopeBiomicroscope and

Metallurgical microscopeParameters

particle size distribution, L/D ratio distribution, circularity distribution, particles and aggregated particles

FEATURES AND BENEFITS

SPECIFICATION

Agglomerated particles Depolymerized particles Flaky particles

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仪器制造商:丹东市百特仪器有限公司网址:www.bettersize.com 邮箱:[email protected] 电话:0415-6184440

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C03=

颗粒数目：

0.706 C06= C10= C16= C25=0.741 0.777 0.807 0.837

2722 最大圆形度：1.000 最小圆形度：0.404 平均圆形度：0.883 跨度：0.241

仪器制造商:丹东市百特仪器有限公司网址:www.bettersize.com 邮箱:[email protected] 电话:0415-6184440

C50= 0.892 C75= 0.941 C84= 0.969 C97= 1.000 C98= 1.000

Particle size distribution Circularity distribution

L/D ratio distribution

• Automatically separation of connected particles

When using particle imaging, aggregated particles have a large influence on measurement results. Unlike manual splitting, the BeVision S1’s automatic segmentation feature helps you get accurate particle information by quickly and accurately separating particles.

• Precise calibration

The actual size of the particles can be accurately calibrated using the scale ruler.


Scans and isolates agglomerated, depolymerized and flaky particles


Measuring range 1 - 9500 nm (sample dependent) Scattering angle 90°

Repeatability error ≤1.0% (GBRM D50) Detector PMT

Accuracy error ≤1.0% (GBRM D50) Correlator 1,000 physical channels

Sample cell volume 4 ml and 1 ml Interface USB 2.0 or USB 3.0

Sample cell temperature control

15 - 90°C Dimensions / Weight680 × 440 × 220 mm (L x W x H) / 25 kg

Dual peak resolution ≥1.65 Operating system Windows 7 or higher

Molecular weight range

1 - 20 kDaEnvironmental requirements

Temperature: 19 - 90℃; humidity: 0 - 95%, no condensation

LaserSolid Fiber Laser (20 mW / 635 nm)

SPECIFICATION


Particle Size Distribution of Proteins, Liposomes and Nanoformulations

NANOPTIC 90

In the field of biopharmacy, there can be ultrafine nanoparticles that play an important role particularly in cancer treatment formulation for example. A protein molecule may possess unparalleled capability in expression, an invisible virus or vaccine molecule may have amazing replicative or immune response performance, a liposome can be the best carrier for some medicine owing to its bilayer structure.

Small particles of proteins, viruses, liposomes, emulsion formulations, exosomes and quantum dots are important in many sections of biopharmacy. However, it is challenging to measure the size of these fine particles precisely. We will help you with our specialized nanoparticle size analyzer Nanoptic 90 capable of measuring down to nanometer size.

Analysis theory: DLS (dynamic light scattering);

The correlator with 1,000 channels and a sensitive photomultiplier tube provide high repeatability and accuracy;

High-power semiconductor laser provides stable light intensity and long lifespan;

Temperature control range of 15 - 90°C, temperature accuracy ≤0.5°C;

Measures the molecular weight of polymer materials through the light intensity of 4 different solvents with light scattering.


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•Nanoptic 90 schematic diagram

Laser

Lens

Temperaturecontrol system

SampleInitial light beam interrupter

Angle of scattering 90°

Scattered light receiver

Detector

Digital correlator

Electronic device of detector

Nanoptic 90 schematic diagram


Measurement fully automatic by CCD camera

Parameters 8 (measured) + 6 (calculated)

Powders metallic and non-metallic

Conformity ASTM ASTM D6393-08/D6393-14

Conformity ISO ISO 3953: 1993

Conformity USP USP32-NF27<616>

Conformity EP EP7.0 07/2010: 20934E

Sieve size 45 - 2000 μm

Amplitude 3 or 14 mm

Tapped frequency 50-300 times per minute (continuous adjustment)

Control terminal PC, PAD, or mobile phone

Connection Wi-Fi

Dimensions / Weight 600 × 350 × 730 mm (L × W × H) / 42kg

Power supply AC 220 V, 50/60 Hz, 230 W

Functional Indicators of Excipients


Measurement of angle of repose

Measurement of bulk and tapped densities

POWDERPRO A1

Excipients are all the substances contained in a dosage other than the active substance. Many pharmaceutical scientists have focused their attention on the production of multifunctional excipients with enhanced performance to meet the needs of formulation experts in terms of production costs, excipients' functionality enhancement and quality of medicine.

For excipients, in addition to the particle size distribution and specific surface area, other functional indicators such as the bulk density, tapped density and flowability are also critical, especially for thinners, binders, disintegrants, lubricants, and flow aids. When we focus on these functional indicators, which method should we choose? What is the test standard? PowderPro A1 Powder Characteristics Tester will face these challenges together with you.

SPECIFICATION

MEASURED AND CALCULATED PARAMETERSPowderPro A1 measures fully automatic:

• Angle of Repose• Angle of Fall• Angle of Spatula (Flat Plate Angle)• Dispersibility• Bulk Density• Tapped Density• Voidage• Cohesion

PowderPro A1 calculates fully automatic:

• Angle of Difference• Compressibility• Uniformity• Flowability Index• Floodability Index

• Sieve Size

CCD camera

Bulk Density

Tapped Density


BETTER PARTICLE SIZE SOLUTIONS

Dandong Bettersize Instruments Ltd.

Website: www.bettersizeinstruments.com

Email: [email protected]

Address: No. 9, Ganquan Road, Jinquan Industrial Park, Dandong, Liaoning, China

Postcode: 118009

Tel: +86-415-6163800

Fax: +86-415-6163800

The product information in this brochure is subject to change due to technical innovation and performance upgrade without notice. This brochure is only for reference. If there is any inconsistency in future, please adhere to the actual product instead. Bettersize instruments shall not be responsible for errors contained herein.

The Bettersize logo is trademark owned by Dandong Bettersize Instruments Ltd.

bettersize solutions for pharmaceutical development-201912 ... · and the appropriate methodology...

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