The study of the applicability of content uniformity and weight variation test - The state of commercial tablets and capsules in Japan

This study intends to determine the rational criteria (e.g., threshold valu e) for applying the weight variation test and to investigate the adequacy o f the acceptance value for existing commercial products in Japan. The studi ed products were 489 lots (3 lots x 163 products) of compressed tablets (pl ain, film-coated, sugar-coated) and 42 lots (3 lots x 14 products) of hard capsules marketed in Japan. The individual drug content and the weight of 1 0 units in a lot were determined for each product and the acceptance values were calculated according to the Japanese Pharmacopoeia thirteenth edition (JP13) Content Uniformity Test (M=100.0, k=2.2). Product-specific intra-lo t relative standard deviation of content (RSDD), weight (RSDW) and concentr ation (RSDC) were calculated by analysis of variance (ANOVA) using three lo ts of data per product. The RSDD and RSDC tended to increase with the decre ase of the label strength for plain tablets, but not for film-coated and su gar-coated tablets, and hard capsules. A good correlation was found between RSDD and RSDC but not between RSDD and RSDW. These findings indicate that 1) it is difficult to rationally set the threshold level for weight variati on, especially regarding the dosage forms except for plain tablets, 2) the application of weight variation tests should, in principle, be decided on t he mixing homogeneity that is RSDC. 3) Most (99.6%) of the tablets and all the capsules investigated met the requirement of content uniformity test of JP13. Therefore the criteria of the JP13 content uniformity test are consi dered acceptable from the viewpoint of manufacturing capability.