Progress in co-crystallization as a separation technology

doi:10.16085/j.issn.1000-6613.2019-0620

Abstract

Abstract:

The separation of small organic molecules by co-crystallization technology, especially the separation of some high-purity APIs that cannot be salted, is the frontier of crystal engineering applications. The principle is to form cocrystal by intermolecular recognition, and to change the lattice energy or solubility characteristics of the target molecule, thereby achieving separation. Aiming at the application of cocrystallization in separation, this paper systematically reviews the examples of co-crystallization in separation and purification of achiral molecules and chiral APIs and intermediates from the thermodynamic principle of cocrystal separation. Separation examples are analyzed from different perspectives such as molecular structure, intermolecular interaction force, solubility product constant, solvent system, etc. For the existing problems of this technology, such as the lack of regularity in the choice of cocrystal formation, the complexity of the actual API purification system, the feasibility of recycling eutectic formation, it is pointed out that establishing the cocrystal formation selection method of the system and in-depth study of thermodynamic behavior are the main research directions in the future.

Key words: separation, crystallization, pharmaceuticals, selectivity

摘要：

使用共结晶技术分离有机小分子，特别是一些不能成盐的、高纯度要求的原料药(API)的分离是晶体工程应用的前沿。其原理是通过分子间的识别作用形成共晶，改变目标分子的晶格能或溶解特性，从而实现分离。针对共结晶在分离中的应用，本文从共结晶分离的热力学原理出发，系统综述了共结晶在分离纯化非手性分子以及手性API及中间体中的实例。从分子结构、分子间的相互作用力、溶度积常数、溶剂体系等不同角度对分离实例进行分析。针对该技术现存的问题如共晶形成物的选择缺乏规律性，实际API纯化体系的复杂性，共晶形成物回收利用的可行性，指出建立系统的共晶形成物选择方法、深入地研究热力学行为是未来的主要研究方向。

关键词: 分离, 结晶, 药物, 选择性

CLC Number:

TQ463

Chengjun JIANG, Guilin CHENG. Progress in co-crystallization as a separation technology[J]. Chemical Industry and Engineering Progress, 2020, 39(1): 311-319.

蒋成君, 程桂林. 共结晶分离技术研究进展[J]. 化工进展, 2020, 39(1): 311-319.

Figures/Tables 24

References 39

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