Dissolution Testing Strategies for Large Sample Sizes and Applications in Continuous Manufacturing

The potential advantages of larger sample sizes for dissolution testing through surrogate modeling in the context of continuous manufacturing and process analytical technology is the motivation for development of a statistically based batch release acceptance criterion. A common approach in conventional batch release is to measure at most 24 tablets in three subsequent stages and evaluate the results against the acceptance criteria of the United States Pharmacopoeia (USP <711> Dissolution). We describe two approaches for a statistically based release testing strategy for immediaterelease dosage forms with N > 24: 1) generalization of USP <711> three-stage acceptance criteria for any sample size greater than 24, and 2) a tolerance interval approach. Both approaches are based on a sample-size independent criterion ensuring a known probability of passing USP <711> acceptance criteria. The proposed criteria can be applied to the entire batch or segmented portions of a single batch run.