Abstract:

Surface-induced nucleation refers to utilize the interaction between solute molecule and heterogeneous surface to regulate the nucleation process. It can not only promote the nucleation by reducing the energy requirement during the process of heterogeneous nucleation but also control crystal polymorphism while without changing solvent, temperature and so on. In recent years, surface-induced nucleation has been widely studied in screening and controlling of polymorphism of active pharmaceutical ingredients. The mechanism of heterogeneous surfaces inducing nucleation for controlling polymorphism is reviewed. In addition, four surface substrates used to induce nucleation for controlling crystal polymorphism including polymers, small organic molecular crystals, self-assembled monolayers and gels are reviewed. Besides, four strategies for selection and design of surface substrates are summarized. At last, we introduce the existing problems about surface-induced nucleation of polymorphism and prospect the future development of this research field.

Key words: drug polymorphism, surface-induce, heterogeneous nucleation, heterogeneous surface

摘要：

表面诱导成核是指在异相成核过程中，利用异质表面与溶质分子的相互作用来调控成核过程。表面诱导成核不仅可以降低成核能垒促进成核，而且可以在不改变溶剂、温度等条件下对晶型进行调控。近年来，表面诱导成核在药物新晶型的筛选和亚稳晶型的调控两方面得到了广泛研究。本文综述了异质表面影响多晶型成核的机理，介绍了用于诱导多晶型成核的四种异质表面——聚合物、有机小分子晶体、自组装单层膜（SAMs）和凝胶，总结了四种表面选择与设计的策略。最后，对目前存在的问题进行了总结，对未来的发展进行了展望。

关键词: 药物多晶型, 表面诱导, 异相成核, 异质表面