化工学报 ›› 2013, Vol. 64 ›› Issue (2): 385-392.DOI: 10.3969/j.issn.0438-1157.2013.02.001

• 综述与专论 • 上一篇    下一篇

药物晶型转化与控制的研究进展

龚俊波, 王琦, 董伟兵, 王静康   

  1. 天津大学化工学院,化学工程联合国家重点实验室,天津 300072
  • 收稿日期:2012-11-08 修回日期:2012-12-24 出版日期:2013-02-05 发布日期:2013-02-05
  • 通讯作者: 龚俊波(1974—),男,博士,副教授。
  • 作者简介:龚俊波(1974—),男,博士,副教授。
  • 基金资助:

    国家自然科学基金项目(21176173);天津市自然科学基金项目(10JCYBJC14200);化学工程联合国家重点实验室开放课题(SKL-CHE-11B02)。

Progress on transformation and manipulation of drug polymorphism

GONG Junbo, WANG Qi, DONG Weibing, WANG Jingkang   

  1. State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • Received:2012-11-08 Revised:2012-12-24 Online:2013-02-05 Published:2013-02-05
  • Supported by:

    supported by the National Natural Science Foundation of China(21176173), the Tianjin Municipal Natural Science Foundation (10JCYBJC14200) and the State Key Laboratory of Chemical Engineering (SKL-CHE-11B02).

摘要: 药物晶型可显著影响药品质量、安全性和有效性,国家"医药工业十二五发展规划"将药物晶型研究列为提升药物质量安全的主要任务和重点技术。本文介绍了药物多晶型的溶解度行为以及晶型转化的液相和固相介导机理,溶剂、添加剂/模板剂对药物晶型的控制有着重要的作用,而物理场效应(超声波、微波、超重力场等)对晶型转化过程起强化效应;过程分析技术的快速发展为晶型转化机理的研究以及过程优化、控制提供了先进手段。未来药物晶型转化与控制的研究将聚焦分子的组装与调控行为、过程分析以及药物的构效关系等方面。

关键词: 药物多晶型, 转化, 控制

Abstract: The drug polymorphism has a profound effect on the quality, safety and efficiency of the drug product.The Twelfth Five-Year Development Plan of China's Pharmaceutical Industry puts forward one of the major development tasks and technologies focused on the improvement in drug polymorphism study to enhance the quality and safety of the drugs.In this paper, the solubility behavior coupled with the solid state and solution mediated transformation of drug polymorphs are introduced and analyzed.In addition, solvent and additive/template play a critical role in the manipulation of drug crystal form.In many cases, physical field (ultrasound, microwave and high gravity-field)-assisted crystallization gives different results for the manipulation of drug crystal form by specific mechanism.Meanwhile, with the rapid development of process analytical technologies, process optimization and control are enhanced through getting more knowledge of drug polymorphism transformation.In the future, the research of transformation and manipulation of pharmaceutical drug polymorphism will focus on the molecular assembly and regulation, process analysis and structure-activity relationship of drugs.

Key words: drug polymorphism, transformation, manipulation

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