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

In silico pharmacology Pub Date : 2024-08-22 eCollection Date: 2024-01-01 DOI:10.1007/s40203-024-00249-6

Jailani Shiekmydeen, Tanisha, Sonam Sharma, Kishor Chakraborty, Dhanapal Chidambaram Kannaiyan, Noohu Abdulla Khan, Rajkumar Malayandi

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Abstract

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.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00249-6.

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利用 PBPK 建模和模拟，优化生产利伐沙班普通速释片剂的湿法制粒工艺。

制粒是开发水溶性差的药物产品的关键工艺。配制不良的产品在溶出和生物等效性研究中面临挑战。利伐沙班（RXB）是一种溶解性较差的药物，在 20 毫克的高浓度下空腹生物利用度为 66%。要确定高强度试验产品和参比产品之间的生物等效性，就必须比较溶解度曲线和生物等效性。制粒不当的产品和其他批次的产品在虚拟生物等效性方面不合格。本研究利用 PBPK 建模和模拟，对生产 RXB 普通速释片剂的湿法制粒工艺进行了优化。此外，PBPK 模型不仅可用于制剂优化，还可用于医药产品开发过程中的工艺优化：在线版本包含补充材料，可查阅 10.1007/s40203-024-00249-6。

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In silico pharmacology

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