Sunday, December 6, 2015

EXPERIMENT 4: DOSAGE PERFORMANCE TEST

OBJECTIVE
To determine the dosage performance test.
To determine the time taken by a group of tablets to disintegrate into small particles in the disintegration test.
To measure the amount of active ingredients that have dissolved in a volume of dissolution medium at the prescribed time in the dissolution test.


INTRODUCTION
A process so-called disintegration is the break-up of a tablet as this is the first step before entering dissolution process. An orally administered drug must disintegrate to attain good absorption of its active substance. In disintegration test, the time required by a group of tablets to disintegrate into small particles under standard conditions is necessary to be counted and recorded. This test is used for quality control purpose. Also, the test is used for batch release and trending of lot-to-lot variations during manufacturing of tablets. However, it is not a bioavailability indicator.
Meanwhile, dissolution testing is used to provide information about in vitro drug release and it is for quality control purpose of course, and to predict in vivo drug release profile as well. There are four dissolution apparatuses standardized and specified in United States Pharmacopeia (USP) General Chapter <711> Dissolution. They are USP Dissolution Apparatus 1 - Basket (37°C), USP Dissolution Apparatus 2 - Paddle (37°C) which is the most common method used, USP Dissolution Apparatus 3 - Reciprocating Cylinder (37°C), and USP Dissolution Apparatus 4 - Flow-Through Cell (37°C).

MATERIALS AND APPARATUS
For disintegration test,
6 tablets, Basket-rack assembly, Disc, a beaker (1 litre), water, disintegration machine.
For dissolution test,
900mL of buffer solution, an ibuprofen tablet, UV-visible spectrophotometer, 50mL of standard solution containing 10mg of ibuprofen, dissolution medium, dissolution vessels, syringe with suitable filter, dissolution machine.

PROCEDURES
Disintegration test for sugar-coated tablets
1. The apparatus for the disintegration test according to its operation manual was set up.
2. The temperature of the disintegration medium (medium) was ensured at 37 ± 2°C
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 in each tube was checked 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, the test using 6 new tablets was repeated but replacing the disintegration medium (water) with 0.1 M hydrochloric acid. Tablets comply with the test if all 6 tablets disintegrate in the acidic medium.
Dissolution test for tablets
1. Each of the dissolution vessel was filled up with the buffer solution to 900 ml mark. The temperature was set to 37°C.
2. The temperature of the dissolution medium was checked.  It was ensured at 37 ± 0.5°C.
3. One Ibuprofen Tablet was placed into each dry basket assembly.
4. The stirring speed was set to 150 rpm. The basket assembly was lowered into position in the vessel and the operation was started.
5. After 30 minutes, 10ml samples of the dissolution medium from each vessel was withdrawn for analysis and the solution was 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, and not less than 10nm from the wall of the vessel. Replace the volume of aliquot withdrawn for analysis with an equal volume of same dissolution medium.
6. A standard solution of Ibuprofen was prepared by diluting 10.0mg of ibuprofen reference standard to 50mL with dissolution medium.
7. 2.0mL of sample solution was diluted and 2.0mL of standard solution to 25mL with dissolution medium in separate volumetric flasks.
8. The absorption of both solutions was measured in a 1 cm cell at a wavelength of 221 nm.
9. The percentage amount of ibuprofen dissolved was calculated using the following formula:
Aṯ /Aṣ . W/50 . 2/25 . P . 900 . 25/2 . 100/200
Where Aṯ = absorbance of sample solution
             Aṣ = 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 were determined whether comply with the requirements of the British Pharmacopoeia. (Assume Q= 75%)








RESULTS


DISINTEGRATION TEST
All six tablets disintegrated completely in 45 minutes.
No residue except for the remaining of fragments of un-dissolved coating.

DISSOLUTION TEST
Absorbance of sample solution,
0.853
Absorbance of the standard solution,
2.270
Weight of ibuprofen reference standard used, W
10mg
Purity of ibuprofen reference standard, P
0.98

Q = Aṯ /Aṣ . W/50 . 2/25 . P . 900 . 25/2 . 100/200
    = (0.853/2.270) x (10/50) x (2/25) x (0.98) x (900) x (100/200)
    = 33.14%


DISCUSSION

The disintegration test is very straightforward. The individual tablets were held in tubes capped with mesh screens that are agitated by reciprocation in the selected medium, which was water. The disintegration test provides a measure of the amount of time necessary for the dosage form to disintegrate into smaller pieces. It does not involve quantitative measurement of drug concentration.
The sugar coated tablets pass the test if each of the six tablets disintegrate in not more than 60 minutes. From the result obtained, all six tablets disintegrated completely within 45 minutes with no residue except for the remaining of fragments of un-dissolved coating. Thus, the tablets have passed the test.

Disintegration is a state in which no residues except for the remaining of fragments of un-dissolved coating o the screen of the test apparatus. If any residue left, it must consists of soft mass having no evident firm unmoistened core. If the tablets were not able to disintegrate completely, the test need to be repeated using hydrochloric acid as the medium.

Dissolution test measures the amount of active ingredients that have dissolved in a volume of dissolution medium at the prescribed time, using an apparatus specially designed according to the experimental parameters. Q is the specified amount of dissolved active substance, expressed as a percentage of labelled content.

For dissolution test, Q = 33.14% which is less than 75% , thus it does not achieve USP standard as expressed as percentage of labelled content. In this test, the tablet dissolve in the dissolution medium as substituents are present. However, the unevenly distribution of active ingredients in the dissolution medium may result in a low percentage of active ingredients. Hence, this will contribute to an error of the experiment. Also, this condition is related to lower soluble of active ingredients thus more time is required to let them dissolve completely.

            Some precaution has to be taken while conducting both tests. First, in order to obtain a more accurate result, the recommended procedures should be followed accordingly without skipping any steps. Second, avoid parallax error by placing the eyes perpendicularly to the scale. Third, the equipment used in the laboratory should be calibrated at least within 6 to 12 months.

CONCLUSION
  • All the 6 tablets comply with the disintegration test.
  • Ibuprofen does not comply with the dissolution test.


REFERENCES





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