Sources of dissolution variability into biorelevant media

Abstract

Identifying sources of dissolution variation is often challenging. Biorelevant dissolution media are compositionally complex, can require multiple steps to fabricate, and are utilized across differing laboratories. The objective was to determine the contributions of location, operator, media fabrication method, day, and tablet to total dissolution variability into biorelevant media. Thirty min dissolution data from a prior report were subjected to analysis-of-variable (ANOVA). Results showed that total dissolution variance was highest for medium dissolution (versus high or low dissolution). Overall, across both ibuprofen and ketoconazole, the rank-order importance of sources of variation were location > operator (nested in sequence) > day > fabrication method > tablet. Location and day were the factors that most frequently were significant sources of variability. However, location was generally much more impactful than day, and location frequently contributed to the majority of total variance. Day never contributed as the majority factor and was generally minor. Fabrication method was occasionally significant, although never a majority contributor. Overall, of all factors, location contributed most to dissolution variance here, using biorelevant media, as observed in other studies not using biorelevant media. This impact of location with and without biorelevant media supports our prior findings that biorelevant media generally showed favorable repeatability and reproducibility.