It is the process through which solid dosage form (tablets, capsules, granules etc.) immediately go into molecular solution.

1. GUIDELINES FOR DISSOLUTION TESTING
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•
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-016
Department of Pharmacy (Pharmaceutics) | Sagar savale

2. Content
• Introduction
• Definition
• Purpose and concept of Dissolution Testing
• Dissolution testing guidelines
1) USFDA guidelines
2) FIP guidelines
• Conclusion
• References
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3. Definition:
•Dissolution:
•It is the process through which solid dosage form
(tablets, capsules, granules etc.) immediately go into
molecular solution.
OR
•It is the process by which a solid substances dissolves
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4. Apparatus
1) USP Apparatus - I (Basket Type)
2)USP Apparatus- II(Paddle Type)
3)USP Apparatus- III(Reciprocating Cylinder)
4)USP Apparatus- IV(Flow Through Cell)
5)USP Apparatus- V(Paddle Over Disk)
6)USP Apparatus- VI(Cylinder)
7)USP Apparatus- VII(Reciprocating Holder)
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5. Purpose & Concept of Dissolution Testing
• Purpose:
1) Bioavailability and Bioequivalence Study
2) In vitro-in vivo comparison
3) Verification
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Concept:
1) In vitro dissolution testing serves as an important
tool for characterizing the biopharmaceutical
quality
of product
2)For evaluation of active ingredients
3) In vitro dissolution data are supportive in the
evaluation of possible risk such as-

7. Guidelines for dissolution testing
• FIP guidelines for dissolution testing of solid oral products
( Final Draft, 1995)
• USFDA guidelines for dissolution testing of immediate
release solid oral dosage forms by Center for Drug
Evaluation and Research (CDER) Aug-1997
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8. FIP Guidelines
In 1981 Federation International Pharmaceutique (FIP)
published “Guidelines for dissolution testing of solid oral
products
During the past decade dissolution test methodology has been
introduced to many pharmacopoeias.
The joint working group on dissolution of the two FIP
sections ,therefore decided to establish a new dissolution
guidelines
FIP will gives biopharmaceutical aspects of in vitro
dissolution testing of solid oral product in Nov 1996
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9. Guidelines for the dissolution
testing
Apparatus
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12. Guidelines for the experimental testing conditions
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13. Experimental Testing conditions
 For basket/paddle methods the volume should be 5oo-1,ooo ml
 The pH of the test medium should be within pH 1.0 - 6.8.
Higher PH justified on case by case basis & not exceed PH 8.
 In the pH range of 4.5 – 8.0 USP buffer solutions are
recommended.
 Agitation typically should be obtained in the basket /paddle
apparatus by stirring at 50-100 rpm and in general should not
exceed 150 rpm.
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14. Experimental Testing conditions cont....
• Flow rate should be set between 8-50 ml/min
• Regarding temperature, 37 ± 0.5
0
c should generally be
used for oral dosage forms.
• De-aeration
• 10-20% or approximately 30% of solubility concentration to
assure that dissolution is not affected by solubility
characteristics.
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15. Guidelines for the dissolution
testing of novel dosage forms
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16. Oral suspension (for systemic use)
• Apparatus- paddle
• Dissolution medium- water
• RPM- for low viscosity(25)
for high viscosity(50-75)
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17. Orally disintegrating tablet
• Taste (drug coating) is very often an essential feature of ODT
& thus can also be the rate determining mechanism for the
dissolution.
• Apparatus-paddle type
• Agitation speed -50 rpm
• Dissolution media- distilled water & pH 6.8
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18. Chewable Tablet
In principle the test procedure for chewable tablets should
be same as that of regular tablet
But the agitation rate should be increased as compared to
conventional tablet
Apparatus- the reciprocating cylinder with glass beads may
provide more intensive agitation speed for in-vitro
dissolution testing
Another option ,mechanical breaking of the tablet prior to
exposing the specimen to dissolution testing, but no
approach for validating such method has been reported.
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19. Transdermal Patches
• Current compendial apparatus- include paddle over disc(USP
apparatus 5), the rotating cylinder(USP apparatus 6), the
reciprocating disc(USP apparatus 7) & paddle over extraction
cell method(ph.Eur.2.9.4.2)
• Paddle over disc is preferred
• pH of dissolution medium- 5-6
• Temperature- 32±0.5
• RPM- 100
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20. Semisolid dosage forms
• Apparatus- Franz diffusion cell
• Depending on the solubility of drug the receptor medium may
need to contain the alcohol or surfactant
• De-aeration at the membrane surface is critical to avoid the
bubble formation
• Temperature- 32 0
C (vaginal creams at 37o
c)
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21. Suppositories
• Rectal temperature- typically 36- 37.50
C
• Dissolution media temperature- 37-38.50
C(which can be
justified in patients fever)
• Apparatus-
For lipophilic suppositories- modified flow through cell
For hydrophilic suppositories- basket method or paddle
method with wire screen
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22. Chewing Gum
• In case of the chewing gum the intensity & frequency of
shearing forces (chewing action) can also have large influence
on drug release rate
• The European pharmacopeias describe the special apparatus
with stainless steel 3-piston apparatus
• Experimental conditions
• Temperature- 370
C
• RPM- 60
• pH of medium 6.4( adults)
7.4(children)
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23. Parenteral, Implant and Microparticulate Formulation
• Implant & Microparticulate: Flow through cell
• For testing of parenteral :flow through apparatus modified
with inner diameter to suit special properties for testing
parenteral i.e. low volume of fluid used in the acceptor
comparment
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24. Qualification & Validation
• An apparatus suitability test with calibrators is a further
important aspect of qualification & validation.
• Qualification of dissolution equipment has to consider critical
parameters such as , temperature of test medium rotation
speed, flow rate & volume to be monitored periodically during
the period of use.
• Validation of analytical procedure applied in dissolution
testing includes , accuracy, precision, linearity & range.
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25. In Vitro-In Vivo Correlations
• Correlation based on:
Plasma level
Urinary excretion data
Pharmacological response
• To achieve an in vitro-in vivo correlation, at least three batches
that differ in the in vivo as well as the in vitro performance
should be available. If the batches show differences in in vivo
performance, then in vitro test conditions can be modified to
correspond with the in vivo data to achieve an in vitro-in vivo
correlation.
• Importance
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26. Possible reasons for poor in vitro-in vivo
correlations
• Study design
Inappropriate In vitro test conditions.
Inappropriate In vivo test conditions.
• Dosage form
Drug release not controlled by the dosage form. ..
Drug release strongly affected by intestinal transport .
kinetics.
• Drug substance
Chemical degradation in the gastrointestinal tract.
Absorption of undissolved particles.
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27. General care and precautions
• Proper handling of the instrument.
• Do not start the heater if there is no water in the tank up to the
mark level.
• While filling the tank with water make sure that water should not
fall on the stirrer unit and on the heater cover.
• Do not pull or force the paddle or basket.
• . Do not over tighten the paddle.
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28. • Do not disturb the sensor tube while cleaning the tank.
• Handle the external probe with care.
• Do not use any pointed objects for setting the parameters.
• While paddles are rotating so first stop the paddle and then
press lift UP switch.
• MAINTENANCE / REPAIRS :-
If the instrument does not produce required calibration
results or its response is poor then it should be labeled
˝FAULTY” and should be repaired or serviced.
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29. Conclusion
1) Guidelines applicable for all involved in dissolution testing.
2) Provide Guidance to
a) Industrial research & development .
b) Process validation & quality control.
c) Drug regulatory authorities
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30. References:
• Banakar U.V., Pharmaceutical Dissolution Testing , A Series
of Textbook and monograph, published by MARCEL
DEKKER,INC, New York, 10016, vol. 49,.1-4
• FIP Guidlines for dissolution testing of Solid Oral Product,
Die pharmazeutics industrie 59: 760-766(1997)
• Sievert M, Dressman J., Shah V., & Brown C. FIP /AAPS
Guidelines for dissolution For in-vitro release testing of novel
Dosage Forms, Disssolution Technologies Feb 2003: 6-15.
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31. • Shah D.H., SOP Guidelines, 352-353
• Drug Information Journal ,USA, 1996 ,vol.30,1071-1083.
• http:// www.fda.gov/ cder/ guidance.htm
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