models used in invitro dissolution

1. Invitro dissolution of drugs
M.SIMRANA FATHIMA
M.PHARMACY
(˘PHARMACEUTICS)

2. DEFINITION
• DISSOLUTION RATE
The physiochemical properties of most of
the drugs that has greater influence on
their absorption characteristics from the
GIT.
• INVITRO DISSOLUTION TEST
Test used to qualitatively assure the
biological availability of a drug from its
formulation.

3. INTRODUCTION
• Dissolution and drug release tests are in-vitro test s that
measure the rate and extent of dissolution or release of
the drug substance from a drug prod uct, usually in an
aqueous medium under specifie d conditions
• The dissolution test is an important quality control
procedure for the drug product and is often linked to
product performance in vivo.
• In-vitro drug dissolution studies are most often us ed for
monitoring drug product stability and manu facturing
process
• Drug dissolution is important test used to evaluate drug
release of solid and semisolid dosage forms. This test
also quantifies the amount and extent of drug release
from dosage forms.

4. • The values that are obtained from the
dissolution study can be quantitatively analyzed
by using different mathematical formulae,
Because qualitative and quantitative changes in
a formulation may alter release of drug and in
vivo performance
• Thus mathematical models can be developed.
This development requires the comprehension
of all phenomena affecting drug release kinetics
and this has a very important value in the
formulation optimization.
• Once a suitable function has been selected, the
dissolution profiles are evaluated depending on
the derived model parameters.

5. IMPORTANCE OF DISSOLUTION
TESTING
• As reliable predictor of in vivo dissolution
performance of drug.
• A rate limiting factor in determining the
physiological availability of drug.
• As quatity control tool for monitoring the
uniformity and reproducibility of production
batches.
• As research tool in optimizing parameter and
ingredients in new drug formulation.
• It is widely accepted in animal experimentation.

6. WHY DISSOLUTION TESTING
• Results from in-vitro dissolution rate experiments
can be used to explain the observed differences
in in-vivo availability.
• Dissolution testing provides the means to
evaluate critical parameters such as adequate
bioavailability and provides information
necessary to formulator in development of more
efficacious and therapeutically optimal
dosageforms.
• Most sensitive and reliable predictors of in-vivo
availability.
• Dissolution analysis of pharmaceutical dosage
forms has emerged as single most important
test that will ensure quality of product.

7. • It can ensure bioavailability of product between batches
that meet dissolution criteria.
• Ensure batch-to-batch quality equivalence both in-vitro
and in-vivo, but also to screen formulations during
product development to arrive at optimally effective
products.
• Physicochemical properties of model can be understood
needed to mimic in-vivo environment.
• Such models can be used to screen potential drug and
their associated formulations for dissolution and
absorption characteristics.
• Serve as quality control procedures, once the form of
drug and its formulation have been finalized

8. FACTORS FOR DESINGING THE
DISSOLUTION TEST
1. FACTORS RELATING TO THE DISSOLUTION APPARATUS
• the design
• size of the container
• shape of the container
• nature of agitation
• speed of agitation
• performance precision of the apparatus
1. FACTORS RELATING TO THE DISSOLUTION FLUID
• composition
• viscosity
• volume
• temperature
• maintainance of sink and non-sink condition
1. PROCESS PARAMETERS
• introduction of dosage form
• sampling technique
1. changing the dissolution fluid

9. IDEAL FEATURES OF A DISSOLUTION
APPARATUS
• simple in design, easy to operate and unstable
under a variety of conditions.
• provides an easy way of introducting the dosage
form into the dissolution medium and once
immersed, holding it in a regular and reliable
fashion.
• eliminates evaporation of the dissolution media
and maintains it at a fixed temperature within a
specific narrow range. (apparatus
thermostatically controlled at 37˚C).
• sensitive enough to reveal process changes and
formulation differences but still yield repeatable
results under identical condition.

10. COMMON DISSOLUTION MEDIA
• purified water
• diluted acid(0.1N Hcl)
• buffered aqueous solution
• simulated gastric fluid(with or without
enzyme)
• simulated intestinal fluid(with or without
enzyme)

11. FACTORS AFFECTING SELECTION OF
DISSOLUTION MEDIA
• DISSOLVED GASES - these sholud be removed prior
dissolution testing
dissolved gas can alter the ph of media
distilled water ph : 6
deaerated water ph : 7.2
• COMPOSITION OF DISSOLUTION MEDIA - enzymes,
surfactant etc
ENZYMES : pancreatin, pepsin are added for degradation
of gelatin which otherwise develop cross-links and with
aging becomes insoluble in media slowing down the
dissolution rate
SURFACTANT
NATURAL SURFACTANT : bile salt, phospholipids
INTESTINAL SURFACTANT :fatty acid, monoglycerides.

12. • PH OF DISSOLUTION MEDIA
ph of dissolution media should be greater than
pka of drug for complete dissolution of drug.
• VISCOSITY OF DISSOLUTION MEDIA
dissolution rate decreases with increase in
viscosity of dissolution media.
• SURFACTANT
the surfactant are added into dissolution
media for improving the wetting characteristics
of the drug Eg : tween80
• TEMPERATURE
37˚C for all dosage form except transdermal
which is 32˚C

13. TYPES OF DISSOLUTION APPARATUS
1. CLOSED COMPARTMENT APPARATUS
USP TYPE-I basket type
USP TYPE-II paddle type
1. OPEN COMPARTMENT APPARATUS(continous flow
through)
USP TYPE-III reciprocating cylinder
USP TYPE-IV flow through cell
USP TYPE-V paddle over disk
USP TYPE-VI rotating cylinder
USP TYPE-VII reciprocating holder
3. DIALYSIS SYSTEM
official or compendial methods

14. DISSOLUTION METHODS
TWO METHOD
• OFFICIAL METHODS
 Rotating basket method
 Paddle method 
 Flow-through method 
 Reciprocating cylinder method 
 Paddle over disk method 
 Rotating cylinder method 
 Reciprocating disk method
• NON-OFFICIAL METHODS.
 rotating static disk method
 beaker method
 flask stirrer method
 peristalsis method
 rotating bottle method
 dialysis method
 diffusion cell

16.  Advantages
• Full pH change during the test
• Can be easily automated which is important for
routine investigations.
 Disadvantages
• Basket screen is clogged with gummy particles.
• Hydrodynamic „dead zone“ under the basket
• Degassing is particularly important
• Mesh gets corroded by HCl solution

18. Advantages
• Easy to use
• Robust
• pH change possible
• Can be easily automated which is important for
routine investigations 
Disadvantages
• pH/media change is often difficult
• Hydrodynamics are complex, they vary with site
of the dosage form in the vessel
(sticking,floating) and therefore may significantly
affect drug dissolution
• Sinkers for floating dosage forms

20. Advantages
• Easy to change the pH
• pH-profiles
• Hydrodynamics can be directly influenced
by varying the dip rate
Disadvantages
• Small volume (max. 250 ml)
• Little experience
• Limited data

22. Advantages
• easy to change media pH
• pH-profile possible
• Sink conditions maintained.
• different modes a) open system b) closed
system
Disadvantages
• Deaeration necessary
• high volumes of media
• labor intensive

24. Advantages:
• Easy to handle
• Sink conditions are
maintained.
• Membrane effect is minimum.
i.e. drug is placed on a disc
at the bottom.
Disadvantages:
• Disk assembly restricts the patch size
• Borosilicate glass
• 17 mesh is standard(others available)
• Accommodates patches up to 90mm.

26. Advantages:
• Equipment (apparatus 1)available with the
manufacturers can be used with
modification as apparatus 6
Disadvantages:
• Large volume of medium is required.
• Drug gets diluted & causes difficulties in
analysis
• Difficult to clean the cylinder.

28. Advantages:
• Convenient method for selecting the
volume of the medium.
• sink conditions can be maintained. -more
sensitivity 
Disadvantages:
• Investment is high because the design is
totally different from standard equipment
already available in industry.

29. UNOFFICIAL METHOD
1.ROTATING/STATIC DISK METHOD
• Developed by late Eino nelson and described by Levy
and Sahli.
• In this method ,the drug is compressed in a non-
disintegrating disc without excipients.
• The disc is mounted in a holder so that only one face of
the disc is exposed to the dissolution medium.
• The holder and disc are immersed in medium and held in
a fixed position as in static disc method and rotated at a
given speed in rotating disc method.
• Samples are collected at predetermined times.
• Surface area of the drug through which dissolution
occurs is kept constant –intrinsic dissolution rate

30. 2.BEAKER METHOD:
• Reported by Levy and Hayes(1960).
• Dissolution medium, 250ml of 0.1N HCl at 37°C placed
in a 400ml beaker.
• Agitation by three blade polyethylene stirrer,5cm
diameter and rotates at 60 rpm.
• Stirrer immersed to a depth of 2.7 cm in medium and in
the center.
• Tablets are placed in a beaker and test was carried out.
• Samples are removed and assayed for the content.
3.FLASK STIRRER METHOD
• Developed by Poole(1969).It includes RBF and a stirring
element similar to that of beaker method.
• RBF used to avoid the formation of moulds of particles in
different positions on the flat bottom of a beaker.

31. 4.PERISTALSIS METHOD:
• To stimulate hydrodynamic condition of GIT tract in an in-
vitro dissolution device.
• It consists of rigid plastic cylindrical tubing fitted with
septum and rubber stopper at both ends.
• Dissolution chamber consists of a space between
septum and lower stopper.
• Dissolution medium is pumped with peristaltic action
through the dosage form.
5.ROTATING BOTTLE METHOD:
• It consists of rotating rack to hold sample drug products
in bottles and they are capped tightly & rotated in 37°C
temperature bath.
• Sample are decanted through a 40 mesh screen and
residue are assayed.

32. 6.DIALYSIS METHOD:
• Cell consist of 32mm inflated membrane.
• Plugged at the lower end by tight fitting cylindrical
perspex box.
• Upper end of the tube held by thin perspex ring inserted
into the tube and secured by an elastic band.
• The cell suspended , from the arm of the tablet
disintegration apparatus and containing the dosage form
in 150ml of distilled water at 37°C.
7.DIFFUSION CELL :
• Static or flow through diffusion cells are used to
characterize invitro drug release and drug permeation
kinetics from a topical drug product eg: Ointment, cream
or transdermal drug product.
• The Franz diffusion cell is static diffusion system used to
characterize drug permeation through skin model.
• The skin is mounted on the Franz diffusion cell and the
drug product is placed on the skin surface.

33. CONCLUSION
• By studying various factors influencing the rate of
dissolution, we can optimize the different properties of
the formulation.
• By conducting dissolution studies we can know the batch
to batch reproducibility.
• We can estimate the solubilty profiles of the drug.
• The best available tool today which can atleast
quantitatively assure about the biological availability of
drug from its formulation is its invitro dissolution.

34. REFERENCE
• Aulton M.E. Pharmaceutics “The Science of
Dosage Form Design”, 2nd Ed.; Churchill
Livingstone.
• D.M.Brahmankar “Biopharmaceutics and
Pharmacokinetics a Treatise”
• Venkateshwarlu “Biopharmaceutics and
Pharmaceutics”, 2nd Ed.
• Leon Shargel “Applied Biopharmaceutics and
Pharmacokinetics”,5th Edition.
• The Science And Practice of Pharmacy by
REMINGTON , 21 st Edition
• C.V.S.Subrahmanyam “Biopharmaceutics and
pharmacokinetics”, -concepts and applications.