Physiologically based absorption modeling to predict bioequivalence of controlled release and immediate release oral products.

Physiologically based absorption modeling was conducted to predict bioequivalence (BE) for immediate release (IR) and controlled release (CR) formulations. In case of the CR formulation of a BCS class 1 drug, sensitivity analyses were conducted to investigate the impact of gastrointestinal (GI) transit time and absorption scaling factors in caecum and colon on formulation PK. The regional absorption profiles of the test and reference formulations were compared to provide additional confidence on the BE predictions. For IR formulation of BCS class 2b drug, the sensitivity of dissolution rate, precipitation time and human permeability were evaluated. Finally for both cases, population simulations were conducted in crossover manner to investigate BE between formulations, and compared with the observed data. These case studies highlight the utility of absorption modeling in prediction of BE. Such modeling can be used for development of innovator and generic products, as well as to address questions arising during regulatory reviews.