Tablet Disintegration Test Tablets must be tested to ensure disintegration. The United States Pharmacopeia (USP) and EP have official standards, including descriptions of the apparatus type dimensions and test conditions (31,32). For instance, EP has two different types of apparatus : 1-one for tablets that are 18 mm or smaller in size, Apparatus A, testing six tablets. 2-Another for larger tablets, called Apparatus B, with a test with three tablets. The technical specifications of the apparatus, the test conditions, and evaluation criteria can be found in the USP or EP. A tablet is considered to have disintegrated when no residue remains on the screen of the apparatus that makes a reciprocating movement in a selected solution. The test is carried out at 378C. The solutions used are distilled water, 0.1 N HCl, pH 6.8 buffer solutions, and the other USP buffer solutions. For instance, modified release coated tablets are kept in acid solution, and they should not disintegrate in two hours. Plain uncoated tablets should disintegrate in no longer than 15 minutes, whereas water-soluble film-coated tablets should disintegrate in less than 30 minutes. Disintegration is considered a prerequisite for dissolution, and in turn, for good bioavailability. Therefore, it is very important that a designed tablet will disintegrate within the time limits or will withstand without disintegration to protect the drug, for instance, in acid conditions sometimes up to five hours. Tablet Friability Test This test shows the strength of tablets against mechanical attrition. In EP 5.0, a tablet friability apparatus and test conditions are described (32). The procedure as follows: If the tablet target weight is less than 650 mg, 20 tablets are weighed. If the tablet target weight more than 650 mg, 10 tablets are sufficient for the test. The drum is rotated 100 times and the tablets are weighed again. No more than 1% weight loss should occur due to breakage. Although 1% friability is permitted in the EP or USP, from the technological point of view it is considered too much. A good tablet formulation and an appropriate manufacturing process should result in tablets with 0% or maximally 0.5% friability. If 1% or higher friability occurs, formulation scientists and process engineers should correct the situation. Selecting appropriate binder and binder concentrations and compressing tablets with a crushing strength value of 90 N or more will result in tablets with low or no friability. Tablet Weight and Drug Content Uniformity During tablet manufacturing, individual tablet weights may vary for many reasons, some resulting from the formulation and others from tooling and equipment. This variation must be within an acceptable range. The EP states that weight uniformity for 20 uncoated or film-coated tablets may deviate between 5% and 10% depending on the tablet weight (32). If tablet weight is 80 mg or less, maximum 10% deviation is permitted. For tablets with weights between 80 mg and 250 mg, 7.5%, and for those weighing more than 250mg, a maximum 5% deviation is permitted. The production of uniform weight tablets is extremely important, and it can only be assured by a free granule flow, selecting the appropriate lubricant/glidant, and punches with tight working length tolerances. On the other hand, drug content uniformity test is based on the individual drug content of theselected number of tablets. According to the EP, 10 tablets are tested. The preparation complies if the individual content is between 85% and 115%. In case of noncompliance, the extension of the test can be found in the EP. Content uniformity test differs from the weight uniformity since the uniform distribution of a drug depends on the manufacturing method. Low-dose drugs, such as 100 mg drug per tablet, require special precautions during manufacture. For instance, dissolving the active in binder solution and spraying onto other excipients, mixing the drug by geometric dilution method during the granulation, and also preferring wet granulation to direct compression. The USP, 30th edition, 2007, requires more strict conditions for uniformity of dosage units on the basis of weight variation or content uniformity. The choice of applying the test depends on the dose and ratio of drug substance. More details are in the USP (31).
