Content uniformity of potent drugs in tablets.

The type of distribution of low dosage drugs that occurs in batches of commercially available tablets has been examined. The uniformity of content of ethinyloestradiol tablets 10 micrograms B.P. from different sources, assessed by single tablet assay showed that three batches exhibited some positive skewness and one marked positive skewness. At the high level of dilution required, the mixing theory indicates that particles of drug must be very fine if acceptable content uniformity is to be obtained. Cohesion of particles impairs the efficiency of the mixing process. It is shown theoretically that unless the drug is dispersed into its component particles the shape of the distribution curve for the content of drug per tablet, in a batch of tablets, will be positively skewed. The relation between the tensile strength of the powdered drug and the degree of skewness of the drug content is also discussed. A positively skewed distribution for tablets containing a small amount of potent drug is unacceptable because this can lead to the presence of relatively large doses of drug in a single tablet. Where one unexpectedly high result occurs in the quality control of the content uniformity of tablets containing potent drugs it is suggested that sufficient single tablet assays be performed to allow the shape of the distribution curve to be assessed. A test for skewness should be included in compendial standards.