Experiment 4 : Dosage Performance Test

Dosage performance tests

Objectives

To determine the ability of sugar-coated tablets to disintegrate in water/0.1M Hydrochloric acid.

Material and Apparatus

Paralfin tablets , Mafenamic acid tablets , Metranidazole tablets , water 

Procedures

1.      Set up the apparatus for the disintegration test according to its operation manual.

2.      Ensure the temperature of the disintegration medium (water) is at 37 ± 2°C .

3.      Set the time to 60 minutes . Introduce one tablet into each tube , add the disk into each tube and start the operation.

4.      Check the tablet in each tube at the end of the operation.

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

    Results

Type of tablets	Disintegration time
Paralgin	Less than 2 minutes
Mafenamic acid	9 minutes
Metranidazole	Within 21 minutes

     Discussion

Disintegration test are subjected for uncoated tablets, sugar coated tablets , enteric-coated tablets, soluble tablets, dispersible tablets, hard capsules, soft capsules and enteric capsules only. The tablet  which was used in this experiment is a sugar coated tablets such as Paralgin and other tablets such as Mafenamic acid and Metranidazole

From this experiment, the tablets has different duration of time to disintegrate but must follow the standard set for this experiment which must disintegrate not more than one hour in water medium. So, all the tablet have succeeded in this test. The time taken to disintegrate Paralgintablets,Mafenamic acid an Metranidazole are less than 2 minutes , 9 minutes and within 21 minutes .However , this results did not really resemble how the preparation would disintegrate in human body as the enviromental conditions might be really different compared to in human body . Multiple parameters to really resemble our body system upon drug intake were not provided in this test. Some of these parameters include the different pH and motility in different parts of gastrointestinal tract.  It might be lot more faster since the motility of human GI tract were quite vigorous and the pH were lower compared to the medium used which are only water.  And preparation might failed  this test but actually they are able to be fully disintegrate in an actual human. Still, this result is still useful in preformulation test so to reduce drug candidates thus to save time and money.

Some precaution need to be taken during this experiment.  Because the coating of a tablet did not subjected to be disintegrate within the time limit.Therefore,  attention should be taken on identifying that the content of the tablet comply with the standard stated and fully disintegrate . When a formulation have reached the time limit but still have bit of it that did not fully disintegrate, check by squishing it to see whether the fragments still have part that did not come in contact with the water (still in it dry hard tablet or dry powdered tablet form). If the first batch did not meet the requirement, the test need to be repeated using same number of new tablet but the medium now is 0.1M hydrochloric acid. Usually, preparation that must succeed dissolution test did not have to do this test.

  

Conclusion

All the tablets succeeded this test which they disintegrate within the time limit , not more than 1 hour . This disintegration duration however might not be the same as in human body due to some environmental differences. 

  

Dissolution test for tablets

      

     Objective

1.    To predict in vivo drug release profile.

2.    To ensure batch-to batch consistency

Apparatus

1.      25ml volumetric flask

2.      Measuring cylinder

3.      Droppers

4.      Dissolution Basket

5.      Dissolution vessel

6.      Syringe

7.      Filter paper

8.      Spectrophotometer

Chemical

1.      Ibuprofen tablet

2.      Buffer solution/ dissolution medium

3.      50ml of 10mg standard solution

Procedures

1.      The dissolution vessel is filled up with the buffer solution to 900ml mark. The temperature is fixed at 37̊ C.

2.      The Ibuprofen tablet is placed into the dry basket.

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

4.      After 30 minutes, 10ml of samples of the dissolution medium are withdraw from the vessel for analysis using syringe with suitable filter.

5.      2.0ml of sample solution and 2.0ml of standard solution is diluted to 25ml with dissolution medium in separate volumetric flask.

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

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

A_(t )/A_s   .W/50  .2/25.P.900 .25/2.100/200

Where   A_(t ) =   absorbance of sample solution

             A_s     =   absorbance of the standard solution

             W        =   weight of ibuprofen reference standard used

             P         =    purity of ibuprofen reference standard.

8.      From the result obtained, the tablets is determined whether it is comply with the requirements of British Pharmacopoiea (Assume Q=75%)

Result

  

Type of Solution	Spectrophotometer Reading
Standard Solution	1.875 ABS
Sample Solution	0.6550 ABS

Calculation

Percentage amount of ibuprofen dissolved:

0.6550/1.875 x 10/50 x 2/25 x 98/100 x 900 x 25/2 x 100/200 = 30.81%

Discussion

The Spectrophotometer Reading for the standard solution of Ibuprofen is 1.875 ABS and the reading for sample solution is 0.6550 ABS. After the calculation, the percentage amount of ibuprofen dissolved is only 30.81%. According to the result obtained, the ibuprofen tablet does not comply with the requirements of British Pharmacopoeia which stated that the percentage of amount of ibuprofen dissolved should be at least 75% to be considered as a complied tablet. This means the active ingredients does not dissolved completely in the dissolution medium.

This may due to some error occurred during the experiment. One of the errors is that there is some of the residues of the ibuprofen tablet are left inside the dissolution basket and unable to dissolve in the dissolution medium which cause the inaccuracy in the result obtained. Besides, impurities may exist in the dissolution medium and cause the ineffectiveness in dissolving the active ingredient of ibuprofen.

There are several precautions that should be followed to increase the accuracy of the result obtained. First, the temperature of the dissolution medium should always maintain at 37 ̊C because it indicates our body temperature, fail to maintain the temperature will affect the percentage of active ingredient dissolved. Secondly, before the apparatus is used, it is important to make sure it is clean to prevent any contamination. Lastly, when using the spectrophotometer, we must make sure the smooth surface of the cubic is cleaned of dust and finger print to prevent inaccurate number of ABS obtained.

Conclusion

In conclusion, the ibuprofen tablet is not complying with the requirement of British Pharmacopoeia because the percentage amount of ibuprofen dissolved obtained is only 30.81% whereby the requirement of British Pharmacopoeia is 75% and above. This is caused by some errors occur during the test and precautions must be taken to ensure the accuracy of the result.

Reference

1.    http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/2011-02-25711DISSOLUTION.pdf

2.    http://www.melbournscientific.com/dissolution-testing-for-quality-control-and-drug-development/

3.   Methods of Analysis: 5. Pharmaceutical technical procedures: 5.3 Disintegration test for tablets and capsules www.who.int/phint/en/d/Jb.7.5.4/