Unit dose sampling and final product performance: an alternative approach.

This article documents a proposed plan for validation testing for the content uniformity for final blends and finished solid oral dosage forms (SODFs). The testing logic and statistical justification of the plan are presented. The plan provides good assurance that a passing lot will perforin well against the USP tablet content uniformity test. The operating characteristics of the test and the probability of needing to test for blend sampling bias are reported. A case study is presented.

A mixture experiment approach for controlling the dissolution rate of a sustained-release tablet.

Several sustained-release tablet formulations with acceptable pharmacokinetic properties were found to be unstable because of the effects of lactose. Because the pharmacokinetic properties were acceptable, an attempt was made at developing stable formulations that reproduced the in vitro drug release characteristics of the unstable formulations. Through the use of a statistically designed mixture experiment, alternative formulations were generated and tested for dissolution. The dissolution data collected in the mixture experiment were used to develop a statistical regression model for identifying formulations with dissolution rates equal to those of the unstable formulations. The form of the regression model was based on the Higuchi equation. The data analysis indicated that it is possible to generate dissolution profiles that reproduce those of the original formulations by adjusting the ratios of Methocel K4MCR Premium and Methocel K100MCR Premium and by replacing the detrimental lactose with calcium phosphate dibasic anhydrous.