Abstract:

Reactive and antisolvent crystallizations are widely used techniques for the manufacture of inorganic and organic chemicals, such as catalysts and active pharmaceutical ingredients. High supersaturation conditions are usually created in these processes, resulting in fast primary crystallization kinetics, especially nucleation rate. Thus fast and sufficient mixing of different reactants or antisolvent and solution before the onset of crystallization is required to avoid the spatial inhomogeneity of supersaturation, which can lead to crystal products with undesirable properties. The analytical and predictive abilities associated with modelling and numerical simulation can provide insights into the mechanisms of the process phenomena and facilitate the design and optimization of operating conditions and crystallization devices. This paper reviews the development of process intensification approaches and modelling studies of reactive and antisolvent crystallizations. Firstly, process intensification studies by means of diverse crystallization devices, external fields and membrane technology are presented. Secondly, population balance equation and extensively adopted micromixing models are introduced, including engulfment model and joint composition probability density function-based micromixing models. Finally, modelling studies on liquid-liquid and gas-liquid reactive crystallizations and antisolvent crystallization are summarized, in which similar studies are analyzed by comparing the predictive performance with each other. In view of the limitations of existing studies, some perspectives on further development and improvement are presented.

Key words: reactive crystallization, antisolvent crystallization, process intensification, micromixing, numerical simulation

摘要：

反应与溶析结晶技术被广泛地用于无机与有机化学品的生产，如催化剂和药物活性组分。反应与溶析结晶过程通常是在高过饱和度条件下进行，具有快速的成核与生长速率，因此需要在结晶过程开始前实现不同反应物或溶析剂与溶液之间快速充分的混合，以避免不良混合造成过饱和度的空间不均匀分布，破坏晶体产品的性质。模型和数值模拟方法的分析和预测能力可以加深对过程现象的机理认识，促进结晶设备和操作条件的优化设计。本文综述了反应与溶析结晶的过程强化方法和数值模拟的研究进展。首先从结晶设备、外加能量场和膜技术辅助结晶三个方面对过程强化研究进行了阐述；然后介绍了数值模拟中常用的微观混合模型，包括涡流卷吸模型和基于联合组成概率密度函数的微观混合模型；最后对文献中的液液反应结晶、气液反应结晶和溶析结晶的数值模拟进行了总结与分析。针对已有研究的不足，提出了未来发展方向的一些展望。

关键词: 反应结晶, 溶析结晶, 过程强化, 微观混合, 数值模拟