The document discusses recent updates in dissolution techniques. It begins with an introduction to dissolution testing and its importance. It then discusses several advancements in dissolution apparatus designs that improve hydrodynamics and allow for faster, more accurate testing of different dosage forms like floating tablets and aerosols. Detection method updates using fiber optics, potentiometric sensors, and FTIR spectroscopy are also covered. The document concludes that dissolution testing continues growing in importance to regulatory agencies and presents challenges to develop new methods to evaluate emerging drug delivery systems.

1. [1]
Recent
Updates in
Dissolution
Techniques Presented by
Swapnil Singh
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH
S.A.S. NAGAR

2. [2]
Flow of Presentation
[2]
Introduction
Application of dissolution
Official dissolution apparatus
Need of advancement
Recent updates
Conclusion and future perspective

3. [3][3]
 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.

4. [4][4]
Product development
Quality assurance
Product stability
Comparability assessment
Biowaivers
Batch to batch quality control
Identification of potential problems in
drug release

5. [5]
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

6. [6]
 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

7. [7]
1.
• Dissolution apparatus
2.
• Dosage form
3.
• Detection techniques

8. [8]
 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
[8] Qureshi SA, Dissolut Technol. 2004;11:13-21.
 Crescent shaped spindle

9. [9]
 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.

10. [10]
 For low dose drugs classical method of dissolution testing is not well suited
[10]
 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.

11. [11]
 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.

12. [12]
 Aerosol
• Have to dissolve in different environment
• No in vitro test system to study aerosols
[12]
 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.

13. [13]
 Controlled release parenterals
• Number of controlled release parenterals marketed products are
increasing
• There is constant need of dissolution testing apparatus
[13]
Non-compendial methods
Sample and separate method Dialysis method
Barzilay R et al., J Pharm Pharmacol.1968;20(1):232-38.

14. [14]
 Sublingual tablets
• Sublingual tablets have to dissolve in different physiological
conditions as compared to gastric conditions
• Current apparatus and methods not simulate these conditions
[14]
 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

15. [15]
 Medicated chewing gum
• Continuous mastication is required for release of drug from medicated
chewing gum making dissolution testing different
[15]
 Single module apparatus
Azarmi S et al., Int J Pharm.2007;328(1):12-21.

16. [16]
 Poorly soluble drugs
• Conventional apparatus fail to correlate pH changes with dissolution
profile, not simulate the release of acid from gastric lining
[16]
 Multi compartment dissolution apparatus
Rohrs BR, Dissolut Technol.2001;8(3):6-12.
1. 1. Gastric reservoir
2. 2. Intestinal reservoir
3. A. Gastric compartment
4. B. Intestinal compartment
5. C. Sample collector
6. D. Filter
D

17. [17]
Updates in detection methods
[17]
 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 mirrors
Bynum K et al., Dissolut Technol.1999;6(4):11-19
pION rainbow fibre
optic

18. [18]
 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

19. [19]
 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.

20. [20]
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

21. [21]
“A person who never made a mistake never tried anything new”
[21]

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