recent updates in dissolution techniques

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Recent

Updates in

Dissolution

Techniques Presented bySwapnil Singh

NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH S.A.S. NAGAR

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Flow of Presentation

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Introduction

Application of dissolution

Official dissolution apparatus

Need of advancement

Recent updates

Conclusion and future perspective

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Amount of drug substance that goes into solution per unit time under

standardized conditions of liquid/solid interface, temperature and solvent

composition

Dissolution is a prerequisite for the drug absorption

Absorption of a drug is possible only when it is present in solution form,

wherein the molecules are independent and assume molecular dispersion

Correlate in vitro with in vivo drug release characteristics

Costa P et al., Eur J Pharm Sci.2001;13(2):123-33.

Introduction

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Applications of dissolution testing

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Product development

Quality assurance

Product stabilityApplications

Comparability assessment

Biowaivers

Batch to batch quality control

Identification of potential problems in

drug release

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Apparatus Name Drug formulation tested

Apparatus 1 Rotating basket Conventional tablets, chewable tablets, controlled release formulations

Apparatus 2 Rotating paddle Orally disintegrating tablets, chewable tablets, controlled release products, suspensions

Apparatus 3 Reciprocating cylinder Chewable tablets, controlled release formulations

Apparatus 4 Flow-through cell Poorly soluble drugs, powder granules, microparticles

Apparatus 5 Paddle over disc Transdermal formulations

Apparatus 6 Cylinder Transdermal formulations

Apparatus 7 Reciprocating disc Controlled release formulations, transdermal formulations

Official dissolution apparatus

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Need of advancement

Pharma industries trying to test more samples in fraction of time

Faster the test faster the product deliver to market

Requirements of increase quantity while increasing quality

Labour intensive process, require many steps, analyst to analyst

variability

Ensure consistency, quality, ease of use and increased productivity

http://www.americanlaboratory.com/913-technical articles

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1. Dissolution apparatus

2. Dosage form

3. Detection techniques

Recent updates

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Coning effect will lead to wrong interpretation of the results

Laminar flow does not mimic the

turbulence flow in the gastrointestinal tract

Improved hydrodynamics, improved product characterization and prevents

accumulation of disintegrating material

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Updates in dissolution apparatus

Qureshi SA, Dissolut Technol. 2004;11:13-21.

Crescent shaped spindle

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During sample withdrawing fluid dynamics of media get disturbed

Low sampling rate, difficult to study fast releasing dosage forms

Hollow shaft sampling method

Withdraw the samples without disturbing the flow dynamics of media

Sampling rate upto 20 seconds per sample is possible

[9] Pillay V et al., J Contr Rel.1998;55(1):45-55.

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For low dose drugs classical method of dissolution testing is not well suited

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Analytical method is not sensitive enough to detect the low concentration of the drug in the formulation

Small-volume dissolution apparatus

Apply gentle agitation important for immediate release tablets

Low material consumption

Results obtained are comparable to official apparatus

Scheubel E et al., Pharmaceutics.2010;2(4):351-63.

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Floating tablets

• Volume of dissolution medium (900 mL) is very high as compared to

stomach content

• Adherence of dosage form on the shaft,

• Problems during sample collection

• Test does not mimic acid release from stomach lining and gastric

emptying through pylorus opening

Modified Rossett-Rice test

[11] Gohel MC et al., Dissolut Technol.2004;11:23-25.

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Aerosol• Have to dissolve in different environment• No in vitro test system to study aerosols

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Davies and Feddah apparatus

Advantages are flexibility to control pH, flow rate, viscosity and all the particles experience same intensity of solvent flow

Updates in dosage form

Dissolution cell

Davies NM et al., Int J Pharm. 2003;255(1):175-87.

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Controlled release parenterals • Number of controlled release parenterals marketed products are increasing • There is constant need of dissolution testing apparatus

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Non-compendial methods

Sample and separate method Dialysis method

Barzilay R et al., J Pharm Pharmacol.1968;20(1):232-38.

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Sublingual tablets • Sublingual tablets have to dissolve in different physiological conditions as compared to gastric conditions • Current apparatus and methods not simulate these conditions

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One unit apparatus

Sreebny LM et al., Gerodontology.1986;5(2):75-99.

1. 1. Funnel 2. Clamp 3. Filter 4. Glass base 2. 5. Stopper 6. Collection tube 7. Buchner flask

X mL dissolution medium Tablet for

testing Tablet residue

Vaccum pump off

Vaccum pump off

Vaccum pump on

To HPLC analysis

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Medicated chewing gum • Continuous mastication is required for release of drug from medicated chewing gum making dissolution testing different

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Single module apparatus

Azarmi S et al., Int J Pharm.2007;328(1):12-21.

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Poorly soluble drugs • Conventional apparatus fail to correlate pH changes with dissolution profile, not simulate the release of acid from gastric lining

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Multi compartment dissolution apparatus

Rohrs BR, Dissolut Technol.2001;8(3):6-12.

1. 1. Gastric reservoir 2. 2. Intestinal reservoir3. A. Gastric compartment4. B. Intestinal compartment5. C. Sample collector6. D. Filter

D

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Updates in detection methods

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Manual sampling is slow process Accuracy is low

Multiple fibre optic system

Advantages Testing procedure is

simplified More economical Accuracy increased

Disadvantages Not used in turbid media The tablet matrix debris builds up on the

probe mirrorsBynum K et al., Dissolut Technol.1999;6(4):11-19

pION rainbow fibre optic

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Dissolution testing using potentiometric sensors

Advantages Insensitive towards undissolved particles and air bubbles Response time of the sensors is fast Used in turbid and complex media Used for measuring nanosuspensions

Disadvantages Each API requires preconditioning of electrode Electrode disturbs flow dynamics of media

Bohets H et al., Anal Chim Acta.2007;581(1):181-91.

• Correlates potential change with

concentration, consists of reference

and standard electrode

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Dissolution studies with FTIR spectroscopic imaging• This technique provides images of a dosage form during there

dissolution

Effect of different factors on drug release can be explored

Mechanism of drug release can be studied

Vanderweerd J et al., J Cont Rel.2004;98(2):295-05.

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Conclusion and future perspective Dissolution testing is growing continuously as a critical technology to

pharmaceutical analysis

Worldwide regulatory agencies are relying on the dissolution test

more and more for relevance to in vivo performance

Many scientist, organizations, manufacturers are actively developing new and more sophisticated apparatus

Gray V et al., Pharm Forum.1997;23:83-97.

As new chemical entities and new drug delivery systems are developed, there are challenge to develop new methods for in vitro drug release determination

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“A person who never made a mistake never tried anything new”

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