Particle Size Limits to Pass the Acceptance Value (AV)-Based USP Content Uniformity Test for Tablets

The papers published by Yalkowsky et al. and Rohrs et al. offer a method to correlate the probability of passing USP content uniformity (CU) test with maximum allowed particle size and distribution. Their work also provides a guidance for setting the particle size specification especially for a low dose drug. However, their methods are developed based on the previous USP CU test and the up-to-date version of USP/NF (e.g., USP42/NF37) has adopted a new Acceptance Value (AV)-based CU criterion. In this study, using the same assumptions and conditions that are utilized in their papers, we develop a new method to calculate the upper limit of particle size that ensures the pass of the AV-based CU test at a given probability (e.g., 0.99). It turns out that, compared to the previous CU test (e.g., the CU test in USP28/NF23), to pass the AV-based CU test, similar but slightly smaller particle size is needed.