结晶过程晶体粒度分布控制研究进展  

Research Progress on Controlling of Crystal Size Distribution (CSD) in Crystallization Process

作　　者：文婷 王海蓉 黄唯 欧阳金波 张春桃 Wen Ting;Wang Hairong;Huang Wei;Ouyang Jinbo;Zhang Chuntao(School of Chemistry and Chemical Engineering,Wuhan University of Science and Technology,Wuhan 430081,China;School of Chemistry,Biology and Materials Science,East China University of Technology,Nanchang 330013,China)

机构地区：[1]武汉科技大学化学与化工学院,武汉430081 [2]东华理工大学化学生物与材料科学学院,南昌330013

出　　处：《化学工业与工程》2021年第4期44-55,共12页Chemical Industry and Engineering

基　　金：国家自然科学基金(21776225和22068002);湖北省教育厅科学技术研究计划重点项目(D20151101)

摘　　要：结晶是一种重要的晶态化学品分离纯化技术,通过结晶过程控制实现晶体产品粒度分布(CSD)的可控定制,对生产高附加值的精细化学品具有重要意义。尤其对于制药工业,CSD不仅会影响药物产品堆密度与溶出速率,还会影响到药品的生物利用度。基于国内外对结晶过程中CSD控制的研究现状,结合相关案例,系统总结了结晶过程CSD控制的方法,简要介绍了美国FDA新倡导的药物质量保证体系QbC模式,重点分析讨论了过程强化和过程控制策略在工业结晶过程CSD控制方面的应用,并对其发展趋势进行了展望。Crystallization is an important separation and purification technology for crystal products in chemical industry,which can effectively achieve tailored preparation of some important crystal product quality,such as crystal size distribution (CSD),via crystallization process control. Therefore,the control of CSD during crystallization processes is of great significance for the production of high value-added fine chemicals. Especially in pharmaceutical industry,CSD can have important effects on not only bulk density and dissolution rate of drug products,but also bioavailability. On the basis of the domestic and international research progresses on the topic of CSD control,the methods of CSD control in crystallization was systemically summarized and the QbC (Quality by Control) mode promoted by FDA was then introduced briefly,and finally the process intensification techniques,the application of process control strategies and the trend of CSD control in crystallization processes were highlighted.

关 键 词：结晶 晶体粒度分布 过程强化 过程控制 QbC模式 

分 类 号：TQ028.5[化学工程]