Shiekmydeen Jailani, Sharma Sonam, Chakraborty Kishor, Kannaiyan Dhanapal Chidambaram, Khan Noohu Abdulla, Malayandi Rajkumar
Department of Pharmacy, Faculty of Engineering and Technology (FEAT), Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu India.
R&D, Alpha Pharma (Formerly Julphar Saudi Arabia), King Abdullah Economic City, Rabigh, Kingdom of Saudi Arabia.
In Silico Pharmacol. 2024 Aug 22;12(2):77. doi: 10.1007/s40203-024-00249-6. eCollection 2024.
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.
The online version contains supplementary material available at 10.1007/s40203-024-00249-6.
制粒是难溶性药物产品药物研发的关键过程。制剂不佳的产品在溶出度和生物等效性研究方面存在挑战。利伐沙班（RXB）是一种难溶性药物，在20毫克的高强度下具有66%的空腹生物利用度。确定高强度试验产品和参比产品之间的生物等效性需要比较溶出曲线和生物等效性。制粒不当的产品和其他批次在虚拟生物等效性方面未通过。本研究通过生理药代动力学（PBPK）建模和模拟，为制造RXB仿制药速释片的湿法制粒工艺优化提供了见解。此外，PBPK模型不仅有助于制剂优化，还可用于药品研发过程中的工艺优化。
在线版本包含可在10.1007/s40203-024-00249-6获取的补充材料。
