溶析结晶在医药领域的研究进展

doi:10.16085/j.issn.1000-6613.2018-1879

摘要/Abstract

摘要：

结晶作为一种传统的分离和提纯工艺，广泛运用于医药、化工、材料等领域。随着对结晶工艺的深入研究和对晶体产品质量越来越高的要求，结晶不再仅仅用于物质的分离和提纯，更重要的是根据产品功能的需要，制备特定结构的晶体。作为结晶的重要组成部分，溶析结晶因其操作简单、能耗相对较低、适用于热敏性物质等优势受到了广泛的关注。本文从溶析结晶相较于其他溶液结晶的不同点出发，重点介绍了溶析结晶热力学、溶析结晶动力学和工艺过程的研究，以及与溶析结晶相关的超临界流体技术和球形结晶技术。溶析结晶热力学关注了溶解度的测定方法和如何通过相图来确定合适的操作条件；溶析结晶动力学，详细描述了间歇、连续溶析结晶动力学模型的建立；工艺过程的研究，包括溶析剂与含有待结晶物质混合、结晶过程的控制和优化。同时本文对溶析结晶目前存在的问题进行了总结，并对未来的发展作了展望。

关键词: 溶析结晶, 热力学, 动力学, 控制和优化

Abstract:

Crystallization, a traditional method for separation, is widely used in pharmaceutical industry, chemical industry, materials, and other fields. With the deep study on crystallization technology and the strict requirement for the quality of product, crystallization is no longer only used for the separation and purification, but also for the preparations of the crystals with specific structure to fabricate specified functional products. As an important part of crystallization, anti-solvent crystallization has attracted much attention because of its simple operation and relatively low energy consumption and suitability for heat sensitive substances. In this paper, starting from the differences between anti-solvent crystallization and other kinds of solution crystallization, the thermodynamics and kinetics were introduced. The thermodynamics was focusing on the determination method of solubility and suitable operating conditions through phase diagram. The kinetics, described the way to establish batch or continuous crystallization kinetics model, and the process of anti-solvent crystallization, including the mixing of anti-solvent and solution, control and optimization of crystallization process, as well as the supercritical fluid technology and spherical crystallization technology that is the methods related to anti-solvent crystallization. Finally, the future development is prospected.

Key words: antisolvent crystallization, thermodynamics, kinetics, control and optimization

中图分类号:

TQ028.6

黄炎, 孙海龙, 孟子超, 唐忠利, 王靖涛. 溶析结晶在医药领域的研究进展[J]. 化工进展, 2019, 38(05): 2380-2388.

Yan HUANG, Hailong SUN, Zichao MENG, Zhongli TANG, Jingtao WANG. Progress in antisolvent crystallization in pharmaceutical field[J]. Chemical Industry and Engineering Progress, 2019, 38(05): 2380-2388.

图/表 5

图1 EES-THF-水体系的相图（红点代表固液相平衡、液液相平衡数据点及每组实验条件下最初的溶液组成）[16]

图2 与在线监测设备ATR-FTIR、FBRM相结合的结晶器设备示意图[16]

图3 混合设备图[25,26,27,28,29]

图4 膜溶析结晶方法示意图[34,35]

图5 溶析结晶的微流体平台的示意图[38]

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