Validation of the Content Uniformity Testing of USP XXI (1985) for Tablets Containing Potent Drugs

Abstract

The content uniformity of tablets containing high potency, low dosage drugs can only be successfully maintained by application of GMP at all stages of the total manufacturing process including both formulation and quality control. This requires both understanding of the pharmaceutical technology involved and appropriate designing of content uniformity test.

The USP XXI (1985) has made the content uniformity test more stringent by applying both tests by attributes and variables, In this study the test has been challenged by using 27 batches of ethinyloestradiol 10 μg tablets having different degrees of homogeneity in powder mixes and tablets.

The results indicate that the test has a weak potential in determining the content uniformity of batches prepared from cohesive drug powders and characterised by skewed distribution of drug content in tablets. It is the same drawback of the USP XX (1980) content uniformity test. This defect is due to the small sample size of 10 unit doses in the first step which is not sufficient to detect the presence of unit dosages containing high drug content in a batch of tablets hawing skewed distribution. Statistical analysis of the results using coefficient of skBwness and nonparametric Lilliefors test has shown that some batches which have passed the USP XXI (1985) content uniformity test are pharmaceutically unacceptable. This indicates the importance of incorporating within the official specifications a test which includes an examination of the type of distribution and hence, increasing sample size is required.