Physiologically based biopharmaceutics modeling to predict bioequivalence of rivaroxaban formulated as conventional tablets, OD tablets, and fine granules

The objective of this study was to develop a highly accurate method for predicting bioequivalence among various oral solid dosage forms containing BCS Class II drugs using Physiologically Based Biopharmaceutics Modeling (PBBM). Rivaroxaban was used as the model drug. Conventional tablets were selected as the reference formulation, while OD tablets (administered with or without water) and fine granules were evaluated as test formulations. Inter-individual variability in gastrointestinal physiological parameters under fasted conditions was incorporated into both in vitro biorelevant dissolution testing and in silico PBBM simulations. The 90 % confidence intervals (CIs) for AUC 0–48 h were accurately predicted. However, the predicted Cmax ratios tended to be overestimated. To improve prediction accuracy, it is essential to more precisely account for both inter-individual and intra-individual variability in gastrointestinal physiology, as well as the influence of formulation excipients.