PRACTICAL 4 : Experiment 4 – Dosage performance tests

Objectives

·         Disintegration test           :          

To determine the time taken needed for tablet to disintegrate and whether it disintegrates properly when placed in a liquid medium under the experimental condition in this experiment.

·         Dissolution test     : 

To determine the amount of active ingredient(s) released from a solid oral dosage form, using a known volume of dissolution medium within a predetermined length of time.

Introduction

Dosage performance test is a series of tests that is composed of the specification in a United States Pharmacopeia (USP) dosage form monograph. An orally administered, non-solution dosage form is usually satisfied by either a dissolution or disintegration process. Disintegration test is only applicable for uncoated tablets, sugar coated tablets, enteric-coated tablets, soluble tablets, dispersible tablets, hard and soft capsules and lastly, enteric capsules. Complete disintegration is defined as that state in which any residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus or adhering to the lower surface of the disc, if used, is a soft mass having no firm core.  At the same time, dissolution testing is used to provide critical in vitro drug release information for both quality control purposes.

Materials and Apparatus

Disintegration Test

·         6 tablets

·         Disintegration medium - water

·         Beaker

·         Disintegration machine - Discs, mechanical device that controls up-down movement, device that control temperature

Dissolution Test

·         Ibuprofen tablets

·         Dissolution medium

·         Ibuprofen standard solution

·         Dissolution tester

·         Spectrophotometer

·         Filter funnel

·         10ml measuring cylinder

·         Dropper

·         50ml volumetric flasks

·         Weighing boat

·         Electronic balance

Procedures

Disintegration test for sugar-coated tablets

1.      The apparatus is set up for disintegration test according to its operation manual.

2.      The temperature of the disintegration medium is ensured to be at 37 ± 2°C.

3.      The time is set to 60 minutes. Then, one tablet is introduced in to each tube and the disk is added into each one. Operation is started.

4.      The tablet in each tube is checked at the end of the operation.

5.      New tablets are used to replace the tablets that did not disintegrate and 0.1M hydrochloric acid is used instead of water.

Dissolution test for tablets

1.       Dissolution vessel is filled with the buffer solution to 900 ml mark. The temperature is set to 37°C.

2.      The temperature of the dissolution medium is ensured to be at 37 ± 0.5°C.

3.      One Ibuprofen Tablet is placed into each dry basket assembly.

4.       The stirring speed is set to 150 rpm. The basket assembly is lowered into position in the vessel and the operation is started.

5.      10 ml samples of the dissolution medium is withdrew using syringes after 30 minutes and the solution is filtered using suitable filter.

6.      A standard solution of ibuprofen is prepared by diluting 10.0 mg of ibuprofen reference standard to 50 ml with dissolution medium.

7.      2.0 ml of sample solution and 2.0 ml of standard solution is diluted to 25 ml with dissolution medium in separate 25 mL of volumetric flasks.

8.      The absorption of both solutions was measured in a 1 cm cell at a wavelength of 221 nm.

9.       The percentage of  amount of ibuprofen dissolved was calculated using the following formula:

At/As × W/50× P × 900 × 2/25 × 100/200

Where

At= absorbance of sample solution

As = absorbance of the standard solution

            W = weight of ibuprofen reference standard used.

P = purity of ibuprofen reference standard.

Result

Disintegration Test

Paralgin Tablets	Disintegration test with water	Time needed to fully disintegrate
6	Pass	1.96 minutes

Dissolution Test

Absorbance of sample solution: 0.683

Absorbance of standard solution: 2.016

Percentage amount of ibuprofen dissolved    = At/As × W/50× P × 900 ×  × 100/200

                                                                        = 0.683/2.016 x 10/50 x 0.98 x 900 x 2/25 x0.5                                                                     = 9.56%

Discussion

            For disintegration test, a paralgin tablet needs 1.96 minutes to disintegrate fully. Since the tablet disintegrates not more than one hour in water medium, hence the result has met the standard result of the experiment. However, in human body, many parameters such as pH and motility of GI tract and many others should be considered if the experiment was meant to really imitate the environment in the body. Despite that, this test is still usable and effective in pre-formulation stage so as to filter and obtain the drug candidates.                                                                       

            In this experiment, there are a few precautions that one should keep in mind. Firstly, when the formulation has reached the time limit set, squish it to enable the content to be in contact with the water. If the first batch of tablet did not meet the requirement, then the test needs to be repeated by using 0.1M HCl to replace water. Lastly, it must be ensured that the water in the beaker is heated up sufficiently.

As for dissolution test, the reading of spectrophotometer for standard solution and sample solution are 2.016 and 0.683 respectively. According to calculation, the percentage amount of ibuprofen dissolved is 9.56%. To be able to comply with the British Pharmacopoeia, the percentage amount of tablet dissolved must at least be 75%. Hence, the tablet does not comply with it.

This may be due to the errors which occurred during the experiment. Firstly, the temperature of the dissolution medium might not be maintained at 37 degree Celcius. Next, when the sample solution is transferred into the volumetric flask, it is not filtered by using the filter. Hence, there will be some small undissolved ibuprofen tablet fragments in it. This in turn results in wrong reading of absorbance. Another error might be the expiration of tablet. Expired tablet may have altered physicochemical properties and causing different result. Parallax error may also occur when measuring the solution in measuring cylinder and other apparatus. Precaution steps should be taken to avoid these errors so that accurate result can be obtained.

Conclusion

As the paralgin tablet has disintegrated within one hour in the water medium, this shows that the tablet has met the standard result for this experiment. For the dissolution test, the ibuprofen tablet did not achieve the standard result as less than 75 % only had dissolved.