Optimization of wet granulation process for manufacturing Rivaroxban generic immediate-release tablets using PBPK modeling and simulations

Granulation is the critical process for the pharmaceutical development of poorly water-soluble drug products. Poorly formulated products have challenges in dissolution and bioequivalence studies. Rivaroxaban (RXB) is a poorly soluble drug and has 66% fasting bioavailability at a high strength of 20 mg. Establishing the bioequivalence between test and reference products for high strength requires comparative dissolution profiles and bioequivalence. Improper granulation products and the rest of the batches failed in virtual bioequivalence. The present study provided insight into the optimization of the wet granulation process for manufacturing RXB generic immediate-release tablets using PBPK modeling and simulations. Furthermore, PBPK models are not only useful for formulation optimization but also for process optimization during pharmaceutical product development.