Friday, December 19, 2014

Experiment 4: Dosage Performance Tests

Title
Dosage performance tests

(A) Disintegration test for sugar-coated tablets

Objective
To test dosage performance of sugar-coated tablets by disintegration.


Date of Experiment
4th December 2014


Introduction

Disintegration is a process that will produce smaller fragments of drugs, which results in drug releasing process from tablets. Tablet disintegration testing is used as a quality-assurance measure. It is not a true predicter of how well the dosage form will release its active ingredient in vivo. The United States Pharmacopiea (USP) sets standards for tablet disintegration testing. The apparatus is relatively simple. It consists of a basket rack holding six plastic tubes open at the top and bottom. The bottom is covered with a 10 mesh screen. The rack is immersed in a suitable liquid at 37˚C. It moves up and down at a specified rate. One tablet is placed into each tube and the time to disintegrate and fall through the screen is noted. 

Disintegration is achieved when there is no tablet fragments remained on the screen. However, the coating fragment may remain. If any other residue remains, it may consist of a soft mass having no palpably firm, unmoisted core.


Apparatus
Spatula, disintegration apparatus.


Materials/chemical
Oralmet, Redon, Ettrocin, Mefa, Uphamol


Experimental Methods
1.      The disintegration apparatus is set up according to its operation manual.



2.      The medium for disintegration is water and the temperature is ensured at 37°+2°C.
3.      The time for this test is set to 60 minutes.
4.      The disintegration apparatus consists of 6 tubes, each tube is then introduced with a tablet using spatula.


5.      A disc is added into each tube to avoid the tablets to floating out from the tubes when it is raised and lowered down.
6.      The operation is started.
7.      After 60 minutes, the tablets is checked in each tube.
8.      Tablets comply with the test if all 6 tablets disintegrate in 60 minutes. The test is repeated using 6 new tablets but replacing the disintegration medium(water) with 0.1M hydrochloric acid if there is any tablet that does not disintegrate. Tablets comply with the test if all 6 tablets disintegrate in the acidic medium.




 (B) Dissolution test for tablets

Objective
To test the dosage performance of tablet by dissolution.


Introduction

Dissolution test is carried out using the specially designed apparatus according to the experimental parameters. Dissolution testing is the most important way to study the release of a drug from a solid dosage form under in vitro conditions. It will affect the bioavailability of a drug from a solid preparation. Like the disintegration test, the dissolution test does not prove that the dosage form will release the drug in vivo in a specific manner but it is one step closer to the absorption process. Again the USP sets standards for the dissolution but often those suggested procedures are modified by the manufacturer to meet the specific needs of the product. This test is most often performed on products that have known absorption problems or known poor solubility. It is also performed on sustained or delayed release products such as enteric coated products. 

This test requires the solution to be tested for concentration of active ingredient over the time. A dissolution profile is then constructed (Time vs Amount Dissolved) and this is compared to the reference compound or standard for the dosage form in being dissolved.


Apparatus
water bath, motor to regulate the basket speed, cylindrical vessel, basket at temperature of 37±0.5̊C


Materials
Ibuprofen tablet, buffer solution, dissolution medium


Procedures

1)      Each of the dissolution vessels is filled up with the buffer solution to 900ml mark. The temperature is set to 37̊ C.     
2)      The temperature of the dissolution medium is checked. It is ensured at    
      37±0.5̊C.
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 the operation is started.
5)      After 30 minutes, 10ml sample of the dissolution medium is withdrawn from each vessel for analysis and the solution is filtered by 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 10mm from the wall of the vessel. The volume of aliquot withdrawn for analysis is replaced with an equal volume 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 and 2.0ml of standard solution to 25ml is diluted with dissolution medium in separate volumetric flask.
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
At/As x W/100 x 2/25 x P x 900x 25/2 x 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
      10) From the results obtained, the tablets are determined whether it comply with   
            the requirements of the United State Pharmacopoiea.
            USP limits: Not less than 75% of the stated amount of C13H1802 dissolved
            in 30 minutes



Results
(A) Disintegration test for sugar-coated tablets
All tablets are disintegrated after 60 minutes


(B) Dissolution test for tablets
Results
Solution of Ibuprofen
Absorption in 1cm cell at a wavelength of 221nm
Standard
0.758
Sample
0.481


Calculation
The percentage amount of ibuprofen dissolved can be calculated using the following formula:

At/As x W/50 x 2/25 x P x 900x 25/2 x 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


After 30 minutes
The percentage amount of ibuprofen dissolved
0.481  x  10  x      x  0.98 x  900  x  25  x 100
    0.758      50       25                                2      200

=55.97%


Discussion
In order for a drug to be absorbed from a solid dosage form after oral administration, it must first dissolve in solution, followed by the break-up of the tablet; a process known as disintegration. The higher the rate of disintegration, the faster the drugs can be absorbed.

The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles which will pass through a mesh screen. Generally, the test is used as a quality assurance tool for conventional dosage forms. Disintegration process is achieved when no tablet fragments remain on the screen. In this experiment, all tablets are disintegrated in the water after 60 minutes. The limitation of this test is that it does not mimic the condition of GIT. As such, there is no guarantee of clinical efficacy. It is not applicable to tablets that must comply with dissolution test.

Dissolution is the process by which a solid solute enters a solution. In pharmaceutical industry, it may be defined as the amount of drug substance that dissolves in solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition.

Dissolution is one of the most important quality control tests performed on pharmaceutical dosage forms and is now used to predict bioavailability.  In some cases, it replaces clinical studies to determine bioequivalence. Dissolution behaviour of drugs has a significant effect on their pharmacological activity. Solid dosage forms may or may not disintegrate when they interact with gastrointestinal fluid following oral administration depending on their design.
           
According to USP limits, it must not less than 75% of the stated amount of C13H1802 dissolved in 30 minutes. From the results obtained, the amount of ibuprofen dissolved is less than 100%. The inaccuracy of results shows that the tablet does not pass the dissolution test. This may happen due to some errors that occur during experiment.


Conclusion
All the tablets are disintegrated in the disintegration test. The highly dissolved tablet will be absorbed faster in the body thus the bioavailability will be increased.


References
1. http://link.springer.com/article/10.1007%2Fs11095-004-1184-4
2. http://www.ncbi.nlm.nih.gov/pubmed/15783064
3. http://pharmatreasures.blogspot.com/2012/02/what-is-difference-between-dissolution.html

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