In vitro dissolution profile comparison using bootstrap bias corrected similarity factor, f₂

In vitro dissolution profile has been shown to be correlated with the drug absorption and has often been considered as a metric for assessing in vitro bioequivalence between a test product and corresponding reference one. Various methods have been developed to assess the similarity between two dissolution profiles. In particular, similarity factor $$ has been reviewed and discussed extensively in many statistical articles. Although the $$ lacks inferential statistical properties, the estimation of $$ and its various modified versions were the most widely used metric for comparing dissolution profiles. In this paper, we investigated performances of the naive $$ estimate method, bootstrap $$ confidence interval method and bias corrected-accelerated (BCa) bootstrap $$ confidence interval method for comparing dissolution profiles. Our studies show that naive $$ estimate method and BCa bootstrap $$ confidence interval method are unable to control the type I error rate. The bootstrap $$ confidence interval method can control the type I error rate under a specific level. However, it will cause great conservatism on the power of the test. To solve the potential issues of the previous methods, we recommended a bootstrap bias corrected (BC) $$ confidence interval method in this paper. The type I error rate, power and sensitivity among different $$ methods were compared based on simulations. The recommended bootstrap BC $$ confidence interval method shows better control of type I error than the naive $$ estimate method and BCa bootstrap $$ confidence interval method. It also provides better power than the bootstrap $$ confidence interval method.