1. In vitro : Dissolution and drug
release testing
SUBMITTED BY-HIMADRI PRIYA GOGOI
Department of pharmaceutics
M pharm 1st year(2nd semester)

2. CONTENTS
• Introduction
• Factors relating to the dissolution apparatus
• Methods of dissolution
• In vitro drug release testing

3. INTRODUCTION
• Dissolution is a process in which a solid substance solubilizes in a given
solvent (mass transfer from the solid surface to the liquid phase.)
• Dissolution testing measures the extent and rate of solution formation
from a dosage form such as tablet, capsule, ointment, etc.
• The dissolution of drug is important for its bioavailability and therapeutic
effectiveness.
• Dissolution can be defined as a physiochemical process by which a solid
substance enters the solvent phase to yield a solution or the transfer of
molecules or ions from a solid state into a solution.

4. • Dissolution rate is defined as the amount of solid substance goes into
solution per unit time under standard conditions of temperature, pH and
solvent composition and constant surface area.
• In the pharmaceutical industry, it may be defined as the amount of drug
substance that goes into solution per unit time under standardized
conditions of liquid/solid interface.
• Dissolution and drug release tests are in-vitro tests that measure the rate
and extent of dissolution or release of the drug substance from a drug
product, usually aqueous medium under specified conditions.

6. Factors relating to the dissolution apparatus
Design of the container
Size of the container
Shape of the container
Nature of agitation
Speed of agitation
Performance precision of the apparatus

7. METHODS FOR DISSOLUTION
There are basically three general categories of dissolution apparatus :
1. Beaker methods
2. Open flow-through compartment system
3. Dialysis concept

8. 1.BEAKER METHOD
• Rotating Basket Apparatus
• Rotating Paddle Apparatus
• The Reciprocating Cylinder Method
• Flow Through cell Apparatus
• Paddle over Disk method
• Cylinder method
• Reciprocating Holder method

9. • Rotating Basket Apparatus
It is basically a closed-compartment, beaker type apparatus.
It comprising of a cylindrical glass vessel with hemispherical bottom
of one litre capacity partially immersed in a water bath.
A cylindrical basket made of #22 mesh is located centrally in the
vessel at a distance of 2 cm from the bottom and rotated by a variable
speed motor through a shaft.
All metal parts like basket and shaft are made of stainless steel .

11. • Rotating Paddle Apparatus
In here, basket is replaced with a stirrer.
A small, loose, wire helix may be attached to the dosage form that
would otherwise float.
This method was first describe by levy and hayes.
The dosage form is allowed to sink in the bottom of the vessel

13. • The Reciprocating Cylinder Method
This apparatus consist of a set of cylindrical flat bottomed glass vessels
equipped with reciprocating cylinder.
The disks are not used.
This method is less suitable for precise dissolution testing due to the amount of
agitation and vibration involved.
E.g. Chlorpheniramine ER tablets, Carbamazepine chewable tablet

15. • Flow through cell Apparatus
The flow through apparatus consists of a reservoir for the dissolution medium
and a pump that forces dissolution medium through the cell holding the test
sample.
This apparatus is feasible for using large volume of dissolution fluid.
This apparatus feasibility for automation of apparatus.
This apparatus is ease of maintaining of sink conditions during dissolution
which is often required for drugs having limited aqueous solubility.

17. • Paddle over Disk method
 In here, stainless steel disk designed for holding transdermal system
at the bottom of the vessel.
The disk/device should not sorb, react with, or interfere with the
specimen being tested.
The disk holds the system flat and is positioned such that the release
surface is parallel with the bottom of the paddle blade.

19. • Cylinder method
This apparatus is also used for evaluation of transdermal products
and is similar to rotating basket apparatus.
Temperature - 32 ± 0.5°
The dosage unit is placed on the cylinder.
Distance between the inside bottom of the vessel and cylinder is
maintained at 25 ± 2 mm

21. • Reciprocating Holder method
The assembly consists of a set of calibrated solution containers, a motor and
drive assembly to reciprocate the system vertically.
Various type of sample holder are used.
This apparatus is used for evaluation of transdermal products as well as non
disintegrating controlled release oral preparation.
The test is carried out at 32°C

23. Advantages of the Beaker Methods
The basket method is the most widely used procedure which confines the solid
dosage form to a limited area which is essential for better reproducibility.
It is advantageous for capsules as they tend to float at the surface thus
minimizing the area exposed to the dissolution fluid.

24. Limitation of the Beaker Methods
Clogging of the basket screen by gummy particles.
Tendency of the light particles to float.
Sensitivity of the apparatus to variables such as vibration, eccentricity, etc.
Rapid corrosion of the mesh in presence of HCl.
Sensitivity of the apparatus to any slight changes in the paddle orientation.
Non-reproducible position of the tablets at the bottom of the flask.

25. 2. OPEN FLOW-THROUGH COMPARTMENT SYSTEM
The dosage form is contained in a small vertical glass column with built in filter
through which a continuous flow of the dissolution medium is circulated
upward at a specific rate from an outside reservoir using centrifugal pump.
Dissolution fluid is collected in a separate reservoir.
E.g. lipid filled soft Gelatin capsule

27. Advantages
No stirring and drug particles are exposed to homogeneous, laminar
flow that can be precisely controlled. All the problems of wobbling,
shaft eccentricity, vibration, stirrer position don’t exist.
There is no physical abrasion of solids.
Perfect sink conditions can be maintained

28. Disadvantages
Tendency of the filter to clog because of the unidirectional flow.
Different types of pumps, such as peristaltic and centrifugal, have
been shown to give different dissolution results.
Temperature control is also much more difficult to achieve in column
type flow through system than in the conventional stirred vessel type.

29. 3.DIALYSIS SYSTEM
Here, dialysis membrane used as a selective barrier between fresh
solvent compartment and the cell compartment containing dosage
form.
It can be used in case of very poorly soluble rugs and dosage form
such as ointments, creams and suspensions.

32. IN VITRO DRUG RELEASE TESTING
• Drug release is the process by which a drug leaves a drug product.
• In vitro drug release testing in rotating basket method:
In vitro release study was carried out by the rotating basket method.
Six tablets of each batch were taken and placed in rotating basket,
respectively.
Then the rotating basket was introduced into 900 mL of each
dissolution medium (water, 0.1 M HCI and pH 6.8 phosphate buffer)
at 37°C 0.5°C with a rotation speed of 100 rpm..5 mL of sample
solution was collected at different time intervals (2, 4, 6, 8, 10, 12 h)
and filtered through hydrophilic membrane.

33. 5 mL of sample solution was collected at different time intervals (2, 4, 6, 8, 10,
12 h) and filtered through a 0.45 um hydrophilic membrane.
1.0 mL of subsequent filtrate was taken accurately to add into a 100 mL
volumetric flask and diluted with the corresponding dissolution medium to 100
mL and mixed well.
The amount of drug dissolved in the dissolution medium was measured using
an UV-visible spectrophotometer at 233 nm.
The same volume of fresh dissolution medium at the same temperature was
added to replace the amount withdrawn after each sampling.
The drug amount of cumulative release was calculated with a standard curve.

34. REFERENCE
• D.M.Brahmankar, Biopharmaceutics and pharmacokinetics- A
Treatise; Vallabh Prakashan, page no-328-333
• Leon Shargel, Applied Biopharmaceutics & Pharmacokinetics; 4th
edition, page no- 429-435
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