Section I 2.

3 4 5 6

Section Name Introduction of Disintegration test Application and Uses Advantages and disadvantage General Principles involved in testing Different Methods Instrumentation (Models)

Table of Contents:Disintegration Test:INTRODUCTION:- Disintegration tests are performed as per the

pharmacopoeial standards. Disintegration is a measure of the quality of the oral dosage form like tablets and capsules. Each of the pharmacopoeia like the USP, BP, IP etc. each have their own set of standards and specify disintegration tests of their own. USP, The disintegration test is performed to find out the time it takes for a solid oral dosage form like a tablet or capsule to completely disintegrate. The time of disintegration is a measure of the quality. This is because, For example,1.) if the disintegration time is too high; it means that the tablet is too highly compressed IF the capsule shell gelatin is not of pharmacopoeial quality or it may imply several other reasons. And also if the disintegration time is not uniform in a set of samples being analysed, it indicates batch inconsistency and lack of batch uniformity.

Disintegration Test Apparatus :-The disintegration test is conducted using the

disintegration apparatus. Although there are slight variations in the different

pharmacopoeias but the basic construction and the working of the apparatus remains the same. 1. The apparatus consists of a basket made of transparent polyvinyl or other plastic material. 2. It has 6 tubes set into the same basket with equal diameter and a wire mesh made of stainless steel with uniform mesh size is fixed to each of these six tubes. 3. Small metal discs may be used to enable immersion of the dosage form completely. 4. The entire basket-rack assembly is movable by reciprocating motor which is fixed to the apex of the basket-rack assembly. 5. The entire assembly is immersed in a vessel containing the medium in which the disintegration test is to be carried out.

6. The vessel is provided with a thermostat to regulate the temperature of the fluid medium to the desired temperature

7. A water bath or other suitable means of maintaining the text fluid in the jar at 37 2oC.

Materials and Solutions:-(medium)

The assembly is to be suspended in a 1L beaker. The volume of the liquid is such that the wire mesh at its highest point is atleast 25mm below the surface of the liquid, and its lowest point is atleast 25 mm above the bottom of

the beaker; one must make sure that the top of the basket rack assembly shouldnt be

submerged. 1. Water. Use distilled water. 2. Hydrochloric Acid. 3. Sodium Chloride. 4. Pepsin.
5. Potassium Phosphate, Monobasic. 6. Pancreatin. 7. Hydrochloric Acid Solution (0.1 M). Dilute 8.5 ml of hydrochloric acid to 1000 ml with

water, or dilute a commercial volumetric solution with water to obtain a final concentration of 0.1 M.
8. Sodium Hydroxide Solution (0.2 M) Dissolve 8 g of sodium hydroxide in, and dilute to

1000 ml with, carbon dioxide-free water, or dilute a commercial volumetric solution with carbon dioxide-free water ta give a final concentration of 0.2 M.
9. Simulated Gastric Fluid. Dissolve 2.0 g of sodium chloride and 3.2 g of pepsin in 500 ml

of water, add 7.0 ml of hydrochloric acid and dilute to 1000 ml with water. The pH is about 1.2..2
10. Simulated Intestinal Fluid. Dissolve 6.8 g of potassium phosphate, monobasic, in 250 ml

of water. Mix with 190 ml of Sodium Hydroxide Solution (0.2 M) and 400 ml of water. Add 10.0 g of pancreatin, mix and adjust the pH of the resulting solution to 7.5 0.1 with Sodium Hydroxide Solution (0.2 M). dilute with water to 1000 ml..2

Disintegration Test Method(Procedure )

The disintegration test for each dosage form is given in the pharmacopoeia. There are some general tests for typical types of dosage forms. However, the disintegration test prescribed in the individual monograph of a product is to be followed.

Uncoated and Plain Coated Tablets

1. assemble the apparatus when the device for raising and lowering the basket-rack assembly is at rest and its cylinder is in the extreme down position;
2. with 2.5 L of water in the cylindrical jar, adjust the apparatus until the level of fluid in the

jar coincides approximately with the mid-line of the upper plastic plate.
3. maintain the temperature of the fluid at 37 2oC by a suitable means as indicated under

4. remove the basket-rack assembly from the water and disassemble; 5. select at random six tablets from the sample and place one in each of the tubes of the basket-rack assembly;
6. place a plastic disk on each tablet, ensuring the orientation specified under and then a

plunger as specified under.

7. re-insert the assembly ln the water and set the machine in motion;

8. the plastic disks should travel up and down freely, exerting a gentle rubbing action on each tablet; 9. after 45 or 60 minutes (see (10) and (11) below), remove the basket-rack assembly from the water;
10. uncoated tablets pass the test if each of the six uncoated tablets disintegrates3 in not more

that 45 minutes; NOTE:-plain coated tablets pass the test if each of the six plain coated tablets disintegrates in not more than 60 minutes. If any of the tablets has not disintegrated at the end of 60 minutes, repeat the test on a further six plain coated tablets, replacing the water in the cylindrical jar with Hydrochloric Acid Solution (0.1 M). The tablets pass the test if each of the six tablets disintegrates within 60 minutes in this acid medium. Enteric Coated Tablets 1. "Uncoated and Plain Coated Tablets", using 2.5 L of Simulated Gastric Fluid in place of water;

2. remove the basket-rack assembly from the Simulated Gastric Fluid and disassemble; 3. select at random six tablets from the sample and place one in each of the tubes of the basket-rack assembly;
4. place a plunger in each tube

5. insert the assembly in the Simulated Gastric fluid and set the machine in motion; 6. at the end of 60 minutes of operation, remove the basket-rack assembly from the fluid and gently rinse with water; 7. enteric coated tablets fail the test if any now show distinct evidence of disintegration; 8. replace the Simulated Gastric Fluid in the jar with 2.5 L of Simulated Intestinal Fluid;
9. remove the plungers, place a plastic disk on each tablet.

10. re-insert the plunger 11. continue the test by setting the machine in motion; 12. after 60 minutes remove the basket-rack assembly from the fluid;

NOTE:-enteric coated tablets pass the test if each of the six tablets disintegrates3 in not more than 60 minutes in the Simulated Intestinal Fluid.

Applications of Disintegration test :

1.Disintegration test is a simple test which helps in the preformulation stage to the formulator. 2.It helps in the optimisation of manufacturing variables, such as compressional force and dwell time. 3.This test is also a simple in-process control tool to ensure uniformity from batch to batch and among different tablets 4.It is also an important test in the quality control of tablets and hard gelatine capsules.

Advantages of Disintegration tests:

This test is simple in concept and in practice. It is very useful in preformulation, optimisation and in quality control.

Disadvantages:
Disintegration test cannot be relied upon for the assurance of bioavailability. Apparatus for Tablets and Capsules:It consists of: Basket-rack assembly Beaker (1 L capacity) Thermostat arrangement Mechanical device (raising and lowering the basket) Immersion fluid.

Basket- rack assembly:Basket made of transparent polyvinyl or other plastic material It consists of six cylindrical glass tubes (length: 77.5+/- 2.5 cm long, internal diameter: 20.7 - 23 mm, wall thickness: 1.0-2.8 mm).

Fig.no.1 Basket- rack assembly The tubes are held in position by two superimposed transparent plastic plates, perforated by six holes having the same diameters as the tubes. (Diameter: 8.8-9.2mm thickness: 57mm)

To the underside of the lower plastic plate is a woven stainless steel wire cloth with a plain square weave with 1.8-2.2mm mesh apparatus and with a diameter of 0.60-0.665mm.

The upper plate is covered with a six holed stainless steel disc, each about 24+/- 2 mm in diameter, which fits over the tubes and holds them between the plastic plates.

DISC:- A cylindrical disc made of transparent plastic is provided for each tube, (Diameter: 20.7+/- 0.15 mm; thickness: 9.5+/- 0.15; relative density: 1.18- 1.20).

NOTE:- There is a thermostat arrangement for heating the liquid and maintaining the temperature at 35 and 39oC.

Dissolution Test:- Dissolution testing is widely used in the pharmaceutical

industry for optimization of formulation and quality control of different dosage forms.
Dissolution is pharmaceutically defined as the rate of mass transfer from a solid surface into the dissolution medium or solvent under standardized conditions of liquid/solid interface, temperature and solvent composition. It is a dynamic property that changes with time and explains the process by which a homogenous mixture of a solid or a liquid can be obtained in a solvent. It happens to chemically occur by the crystal break down into individual ions, atoms or molecules and their transport into the solvent.

Dissolution testing is a critical preformulation solubility analysis research tool in the process of drug discovery that entails measuring the stability of the investigational product, achieving uniformity in production lots and determining its in vivo availability. Thus this Dissolution testing is an essential requirement for the development, establishment of in vitro dissolution and in vivo performance (IVIVR), registration and quality control of different dosage forms. APPLICATION OF DISSOLUTION TEST

Dissolution testing is widely used in the pharmaceutical industry for optimization of formulation and quality control. It is useful in the pharmaceutical and biotechnology industry to formulate drug dosage forms and to develop quality control specifications for its manufacturing process. To identify the critical manufacturing variable, like the binding agent effect, mixing effects, granulation procedure, coating parameters and comparative profile studies. To comply with guidelines set in the scale up a

nd post approval changes (SUPAC) and ICH. To select candidate formulation To simulate food effect on bio availability. To support waiver for bio equivalence requirements. In the study of Bio waivers. As a Surrogate for invivo studies. In the In vitro invivo correlations.