制药结晶中的先进过程控制

doi:10.11949/0438-1157.20190728

摘要/Abstract

摘要：

结晶作为固-液分离的重要手段，是实现医药产品高端高值化的关键技术。药物结晶过程的精准控制决定了晶体产品的多晶型、晶习、粒度及粒度分布等诸多特性，对生产效率和产品质量的提升具有重要的意义。基于国内外对药物结晶过程控制的研究现状，结合相关案例，系统总结了制药结晶中先进过程控制的理论模型、监测手段和控制策略，重点分析讨论了过程控制在产品工程中的应用并对其发展趋势进行了展望。

关键词: 结晶, 过程控制, 粒数衡算, 过程分析技术, 产品工程, 复杂体系

Abstract:

As an important means of solid-liquid separation, the crystallization from solution is a key technology for achieving high value of pharmaceutical products. The precise control of pharmaceutical crystallization process can tailor the solid properties such as polymorph, crystal habit, particle size and particle size distribution, which has a significant effect on the overall efficiency of the solid production process and the quality of the final product. On the basis of the domestic and international research progresses on the topic of pharmaceutical crystallization and process control, this review systemically summarizes the theoretical models, monitoring methods and control strategies of advanced process control of pharmaceutical crystallization. It will mainly focus on the analysis and discussion of the application of process control technologies in product engineering and the trend of development towards complex systems.

Key words: crystallization, process control, population balance model, process analytical technology, product engineering, complex system

中图分类号:

TQ 028.5

赵绍磊, 王耀国, 张腾, 周丽娜, 龚俊波, 汤伟伟. 制药结晶中的先进过程控制[J]. 化工学报, 2020, 71(2): 459-474.

Shaolei ZHAO, Yaoguo WANG, Teng ZHANG, Lina ZHOU, Junbo GONG, Weiwei TANG. Advanced process control of pharmaceutical crystallization[J]. CIESC Journal, 2020, 71(2): 459-474.

图/表 4

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