Experiment 4 ; Dosage Performance Tests

Title :

Dosage Performance Tests

Introduction :

                         Tablet is defined as a compressed unit solid dosage form containing medicaments with or without excipients. According to Indian Pharmacopoeia, pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drugs or a mixture of drugs, with or without diluents. Sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or order. The sugar coat also enhances the appearance of the compressed tablet and permit imprinting manufacturing’s information. Sugar coating provides a combination of insulation, taste masking, smoothing the tablet core, colouring and modified release.

                          Disintegrating agent is always added to tablet formulation to facilitate its breaking when it contact with water in gastrointestinal tract. It’s aim is to increase the surface area of the tablet fragments and thus promote release of the drug. A good disintegrant will quickly break up a tablet into primarily particles and ensure that the drug is assimilated at a fast rate. Disintegrants act by swelling in the presence of water to burst open the tablet. Starch is the most common disintegrant in tablet formulation. Example of starch derivatives are Primogel and Explotab. Other common disintegrants include cation exchange resins, cross-linked polyvinylpyrrolidone, modified starches (sodium starch glycollate) and cellulose materials. Superdisintegrants swells up to ten fold within 30 seconds when contact water. Examples include Crosscarmellose and Crosspovidone. Evaluation of carbon dioxide in effervescent tablets is also one way of tablet disintegration.

                        Whereas dissolution or solvation is the process by which a solute forms a solution in a solvent. The solute, in the case of solids, has its crystalline structure disintegrated as separate ions, atoms, and molecules form. The outcome of the process of dissolution which is the amount dissolved at equilibrium, is governed by the thermodynamic energies involved, such as the heat of solution and entropy of solution, but the dissolution itself (a kinetic process) is not. Dissolution testing has emerged in the pharmaceutical field as a very important tool to characterize drug product performance. In formulation development, dissolution testing can aid in the selection of excipients and help optimize the manufacturing process, The significance of a dissolution test is based on the fact that for a drug to be absorbed and available to the systemic circulation, it must previously be dissolved Therefore, dissolution tests are used not only for quality control of finished products, but also to assess several stages of formulation development, for screening and proper assessment of different formulations.

Procedures :

Disintegration test for sugar-coated tablets

1. The apparatus is set up for the disintegration test according to it’s operation manual.

2. The temperature of the disintegration medium (water) is ensured at 37+2’C.

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

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

5. If all 6 tablets disintegrate in 60 minutes, then tablets comply with the test. If there is any tablet that does not disintegrate, the test is repeated using 6 new tablets but the disintegration medium (water) is replaced with 0.1M 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 is filled up with the buffer solution to 900ml mark. The temperature is set to 37’C.

2. Temperature of the dissolution medium is checked and ensured it is at 37+0.5’C.

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 operation is started.

5. 10ml samples of the dissolution medium is withdrawed from each vessel after 30 minutes 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, and not less than 10mm from the wall of 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 flasks.

8. The absorption of both solutions is measured in a 1cm cell at a wavelength of 2.21nm.

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

                  At/As x W/50 x 2/25 x P x 900 x 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. Whether the tablets comply with the requirements of the United States Pharmacopoeia is determined from the results obtained.
USP limits : Not less than 75% of the stated amount of C13H18)2 dissolved in 30 minutes.

Results and Calculations:

Disintegration test for sugar-coated tablets

Table 4.1 Disintegration times for the sugar-coated tablets in 37’C water bath
The result is 4.77minutes for the 3 tablets to fully disintegrate. The drug used is NSAID.

Dissolution test for tablets

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

At = absorbance of sample solution
As = absorbance of the standard solution
W = weight of ibuprofen reference standard used
P = purity of ibuprofen reference standard

As a calculation:

At=0.5182, As=0.4988, W=10 grams, P=0.98

0.5182/0.4988 x 10/50 x 2/25 x 0.98 x 900 x 25/2 x 100/200
=84.90%

Discussion:

                    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 many more. Sugar-coated tablets we used in ecperiment, Ibuprofen comply with Disintegration test for tablet. The specification test state that all of the coated tablets should disintegrate within 15 minutes. The end point was determined when there were no particles or granules remaining in the discs. The average disintegration time for 3 tablets are 8.77 minutes which shown in table 4.1. Three of the tablets are of same brand, so they have similar disintegration time. Ibuprofen is a propionic acid derivative that belong to the class NSAID. Disintegration result show that Ibuprofen tablets developed resistance to strong acid. Thus, it will not disintegrated in stomach, preventing complications like gastric pain.

                    Dissolution test is to measure the amount of active ingredient the has dissolved in a volume of dissolution medium at the prescribed time, using an apparatus specially designed according to the experimental parameters. It is the amount (percentage) that must be dissolve in time (minutes).For dissolution test for tablet, the percentage amount of ibuprofen dissolved are 84.90%. This show that the tablet comply with the requirement of the United States Pharmacopoeia (not less 75% of the stated amount of C13H18O2 dissolved in 30 minutes.

Conclusion :
                      As a conclusion, disintegration test is used in the pharmaceutical industry for evalution of disintegration capability of formulations (ex:tablets) and quality control of different dosage forms. Dissolution test is one of the most important quality control tests performed on pharmaceutical dosage forms and is now developing into a tool for predicting bioavailability, and in some cases, replacing clinical studies to determine bioequivalence. Dissolution behavior of drugs has a significant effect on their pharmacological activity.

References :

1. Aletaha, D.; Smolen, J. S. Advances in anti-inflammatory therapy. Acta Medica Austriaca., v.29, n.1,        p.1-6, 2002.
2. http://www.pharmainfo.net/tablet-evaluation-tests/dissolution
3. http://www.pharmainfo.net/disintegration-test