Practical 3(4): Dosage Performance Tests

DISINTEGRATION TEST FOR SUGAR-COATED TABLETS

OBJECTIVE

1. To study and evaluate disintegration test for sugar-coated tablets.

2. To determine whether sugar-coated tablets disintegrate within 60 minutes when placed in a liquid medium at 37^oC.

INTRODUCTION

     Coated tablets are tablets covered with one or more layers of mixtures of substances such as natural or synthetic resins, polymers, gums, fillers, sugars, plasticizers, polyols, waxes, colouring matters, and flavouring substances. The tablets maybe coated for a variety of reasons such as protection of the active ingredients from air, moisture or light, masking of unpleasant tastes and odours or improvement of appearance. The substance used for coating is usually applied as a solution or suspension. 

     In this experiment, the apparatus used is basket-rack assembly which consists of six open-ended transparent tubes. The tubes are held in a vertical position by two plates with six holes, equidistant from the center of the plate and equally spaced from one another. A suitable means is provided to suspend the basket-rack assembly from the raising and lowering device using a point on its axis. 

METHOD

Apparatus

Basket-rack assembly and disks

Materials

Sugar-coated tablets, distilled water

Procedures

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

2.      The temperature of the disintegration medium (water) was ensured at 37±2^oC.

3.      The time was set to 60 minutes. One tablet was introduced into each tube, the disk was added into each tube and the operation was started.

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

5.      The tablets comply with the test if all 6 tablets disintegrate in 60 minutes. If there is any tablet does not disintegrate, the test was repeated using 6 new tablets by replacing the disintegration medium (water) with 0.1M hydrochloric acid. The tablets comply with the test if all 6 tablets disintegrate in the acidic medium.

RESULTS

All the 6 tablets disintegrate in the disintegration medium (water) within 60 minutes.

DISCUSSION

         When a tablet is administered into body, it must be first disintegrate into smaller particles before it is absorbed into body. In this experiment, disintegration test of tablets is carried out by putting it in a basket-rack assembly, which will be lowered into disintegration medium(water) at 37^oC  for 60 minutes. The tablet is continually hammered by a plastic disk to stimulate in vivo conditions. At the end of the experiment, all the 6 tablets have been disintegrated within 60 minutes, thus the tablet is considered to pass the test providing if no tablet residue remains on the mesh after 60 minutes. When the time limit (60 minutes) has been reached, there is still a little amount of fragments of the tablets left, squish it using finger to check whether the fragments are coating or they have not been disintegrated yet. After squishing, if the fragments crack, the fragments proved to be coating and tablets considered to pass the disintegration test. If the fragments are hard and do not break, then the fragments fail in the disintegration test. Hence, the test needs to be repeated using same number of tablets but in the medium of 0.1M hydrochloric acid. In this testing, after squishing, all the tablets crack and success in the disintegration test.

          However, this test is not a true indicator about how well the dosage form will release its active ingredient in vivo. This is due to some limitations. Firstly, it does not mimic conditions of gastrointestinal tract such as the peristaltic movement. Secondly, this test is controlled by experimental variables. There are a few errors occured in this experiment. The dissolution medium is not heated up adequately. Hence, it affects the disintegration process and integration rate. To reduce this error, use a thermometer to measure the temperature of the disintegration medium is constant (37±2^oC).

      

CONCLUSION

All the tablets disintegrate in the disintegrate medium (water) within 60 minutes, thus the tablets comply with the disintegration test.

REFERENCE

1. http://www.who.int/medicines/publications/pharmacopoeia/Tabs-GeneralMono-rev-FINAL_31032011.pdf

2. http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/generalChapter701.pdf

B. Dissolution test for tablets

OBJECTIVE

To determine the percentage amount of Ibuprofen tablet dissolved in the dissolution medium.

INTRODUCTION

         Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) and used as an analgesic and antipyretic. It has a pKa value of 4.5 and is poorly absorbed in water. Drug dissolution is the rate limiting step in the drug absorption process. Paddle method used at a paddle speed of 150rpm, in dissolution medium at 37±0.5^oC, with UV spectrophotometer. The ibuprofen concentration is spectrophotometrically determined at 221nm using the following formula:

        The dissolution test is a simple and useful in vitro tool that can provide valuable information about drug release similarity among different batches and brands. It describes about manufacturing reproducibility, product performance similarity and bioavailability of drug from its formulation.

Structure of Ibuprofen

METHOD

Apparatus:

Tablet dissolution tester with paddle, spectrophotometer, droplet, syringe, beaker, 50mL volumetric flask, stopper, cuvette

Materials:

Ibuprofen tablet, distilled water, buffer solution, standard ibuprofen solution,

Procedures:

1.      Each of the dissolution vessels is filled up with the buffer solution to 900ml mark. The temperature to 37^oC.

2.      The temperature of the dissolution medium is checked. It is ensured at 37±0.5^oC.

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

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

5.      After 30 minutes, 10ml samples of the dissolution medium is withdrawn from each vessel for analysis and the solution is filtered using suitable filter. Sampling should be done from a point half-way between the surface of the dissolution medium and the top of the rotating basket, not less than 10mm from the wall of the vessel. The volume of aliquot withdrawn for analysis is replaced with an equal amount of same dissolution medium.

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

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

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

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

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

10.  From the results obtained, the tablets are determined whether comply with the requirements of the United States Pharmacopoeia. 

RESULTS

Absorbance of sample solution At	0.985
Absorbance of standard solution, As	0.767

DISCUSSION

       The percentage amount of Ibuprofen is 113.27%, more than 75% of the stated amount of C₁₃H₁₈O₂ dissolved in 30 minutes. Hence, Ibuprofen dissolves in the dissolution medium and achieves the USP standard. The active ingredient dissolves throughout the dissolution medium thus the percentage of active ingredient is low. This indicates the active ingredient soluble in the medium quickly and takes less time to become soluble completely.

      There are a few important aspects that need to take into account during the experiment. Firstly, the temperature of the dissolution medium should be monitored and maintained at 37±0.5^oC. Lower temperature may cause poor dissolution of Ibuprofen tablets, while higher temperature may alter the composition of the ibuprofen tablet. The stirring speed should be maintained at 150rpm. Low speed causes slow dissolution rate. The duration of stirring should be set at 30minutes. There should be no air bubbles inside the syringe when taking sample solution and standard solution. The cuvette should be hold at the gross side as holding at the smooth side will left the fingerprints on the surface and affect the result of spectrophotometer.

CONCLUSION

The percentage amount of Ibuprofen is 113.27%, more than 75% of the stated amount of C₁₃H₁₈O₂ dissolved in 30 minutes, thus it comply with the requirement of United States Pharmacopoeia for tablet’s dissolution test.

REFERENCE

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630726/

2. file:///C:/Users/ms/Downloads/Paper-6.pdf