recent updates in dissolution techniques
TRANSCRIPT
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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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