Mass variation tests for coating tablets and hard capsules: rational application of mass variation tests.

The mass variation test is a simplified alternative test version of the content uniformity test. In the case of coating tablets and capsules, the mass variation test is principally applied to test the inner cores or fillings containing the active ingredient. However, some exceptions exist in pharmacopoeias. The effects of tablet coating and capsule shell on the results of the mass variation test were studied. The mass variation of outer crusts (coatings, capsule shells) and inner cores (core tablets, fillings) was measured separately in several products. The effects of coating on weight variability were very large for sugar-coated tablets. Relative standard deviation (RSD) of the formulation weight (RSD(W)) of sugar-coated tablets (2.73%) was larger than that of plain tablets (0.77%). The cause of the large RSD(W) is the large variation the weight of sugar-coating accounting for 44% of formulation weight. In the case of film-coated tablets, the effect of coating weight on the mass variation test was very small because the rate of coating in comparison to the whole weight was small. In the case of hard capsules, the usage of whole formulation weight resulted in underestimation of variations of filling weight. The differences between dosage forms in the applicability of the mass variation test are caused by differing weight proportions and variability of the outer coatings or shells. To avoid the underestimation of mass variation for hard capsules, a corrected acceptance value is useful. For all the dosage units, the mass variation test can principally be applied to determine which mass is expected to be proportional to the content of the active ingredient. However, some modification of acceptance values enables application of the mass variation tests to inapplicable cases, such as when the RSD of drug concentration (RSD(C)) is larger than 2%.