This work focuses on an important problem that is the modeling and control of polymorphic crystallization of indomethacin (IMC) in which one of the crystal forms consists of hair-like crystals. The lack of kinetic knowledge impedes the seeking for methods of efficient polymorph control of IMC. Herein, kinetics of antisolvent crystallization of α-IMC and γ-IMC were first time determined on the basis of experiments and the population balance equation (PBE). It was found that γ-IMC has an advantage in the secondary nucleation rate. A higher temperature was more unfavorable for obtaining γ-IMC under the same supersaturation because the γ-IMC was at a disadvantage in both primary nucleation and growth rates. According to the results of population balance modeling, the primary nucleation rate of γ-IMC only affected the polymorphic composition at the early stage of antisolvent crystallization. The growth rate of α-IMC is the key in effectively controlling the polymorph outcome.

中文翻译：

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多晶型吲哚美辛反溶剂结晶的动力学和群体平衡模型

这项工作重点关注一个重要问题，即吲哚美辛（IMC）多晶型结晶的建模和控制，其中一种晶型由毛发状晶体组成。动力学知识的缺乏阻碍了寻找有效的 IMC 多晶型控制方法。在此，首次根据实验和群体平衡方程（PBE）确定了α-IMC和γ-IMC的反溶剂结晶动力学。研究发现γ-IMC在二次成核率方面具有优势。在相同过饱和度下，较高的温度更不利于获得γ-IMC，因为γ-IMC在初次成核和生长速率方面都处于劣势。根据群体平衡模型的结果，γ-IMC的初级成核速率仅影响反溶剂结晶早期的多晶型组成。 α-IMC的生长速度是有效控制多晶型结果的关键。