药物多晶型的过程控制和工程技术进展

Progress in the Process Control of Pharmaceutical Polymorphism and Engineering

多晶型现象在药物结晶领域普遍存在。同一种药物的不同晶型尽管化学组分相同,却具有不同的理化性质,因此晶型是药品研究和开发的一个重要内容。从药物质量控制角度来看,药物晶型的不同可能会引起生物利用度的差异,不仅会影响到药物的稳定性和后续加工(过滤、干燥、制剂等)过程,而且会影响到药物的临床效果。本文从药物晶型的筛选与控制、结晶过程分析以及工程技术进展等方面对近年来药物结晶工业的发展情况进行总结和分析,并从连续结晶技术和数值模拟等方面展望了药物结晶工业未来的发展方向。

Polymorphism is a prevalent phenomenon for drugs. Polymorphs of one drug are chemically identical, however, their physical and chemical properties are different. Therefore, polymorphism is an important part of research content for drugs. In terms of drug quality control, bioavailability of various polymorphs may be different. Polymorphism is an important factor for the clinic effect of drugs, and has strong influence on the stability of drug crystallization and the post processing （filtration, drying, preparation, et al）. Progresses on the screening and control of polymorphism, process analysis of crystallization, and engineering were summarized and analyzed in this article. Perspectives of development of continuous crystallization and the numerical simulation for industrial crystallization in the future were also given.