Probability of passing dissolution acceptance criteria for an immediate release tablet.

During development of solid dosage products, a pharmaceutical manufacturer is typically required to propose dissolution acceptance criteria unless the product falls into Biopharmaceutics Classification System (BCS) class I, in which case a disintegration test may be used. At the time of filing the new drug application (NDA) or common technical document (CTD), the manufacturer has already met with regulatory agencies to discuss and refine dissolution strategy. The dissolution acceptance criteria are based on stability and batch history data and are often arrived at by considering the percentage of batches that pass United States Pharmacopeia (USP) criteria at Stage 1 (S(1)), when in fact, the product is deemed unacceptable only when a batch fails USP criteria at Stage 3 (S(3)) [H. Saranadasa, Disso. Technol. 7 (2000) 6-7, 18 [1]]. Calculating the probability of passing (or failing) dissolution criteria at S(1), S(2), or S(3) can assist a manufacturer in determining appropriate acceptance criteria. This article discusses a general statistical method that was developed to assess the probability of passing the multistage USP test for dissolution and how it was applied to an immediate release tablet formulation. In this case, acceptance criteria were set and the analysis was conducted to assess the probabilities of passing or failing based on this acceptance criterion. Whether the acceptance criteria were relevant to the product was also considered. This mathematical approach uses a Monte Carlo simulation and considers a range of values for standard deviation and mean of historical data.