A Molecular Simulation Approach to Control the Crystallization of Pharmaceutical Compounds During Dissolution

摘要该项目旨在了解在表面活性剂存在下亚稳固相溶解过程中控制结晶的分子过程。目的包括确定亚稳固相在稳定分子晶体成核中的作用，并解释表面活性剂结合对成核机制和晶体形态的影响。实验将以二水合卡马西平为模型药物，采用脂肪长链表面活性剂和胆盐两种表面活性剂进行。分子模型将用于研究晶体学参数和优势晶面分子结构的作用。关键的问题是，稳定晶相的成核是否被溶解的亚稳相的晶体表面所增强。如果成核发生在非常低的过饱和度，溶液中的药物浓度可能永远达不到所需的水平。表面活性剂对成核和结晶影响的研究结果对制药工业特别有用，也可能对特种化学品的制造产生影响。

CTS - 9526328 Nair Rodriquez-Hornedo University of Michigan ABSTRACT The project aims at understanding the molecular processes that control crystallization during dissolution of metastable solid phases in the presence of surfactants. The objectives include identifying the role of metastable solid phases on the nucleation of stable molecular crystals and explaining the effects of surfactant association on nucleation mechanism and crystal morphology. Experiments will be performed using dihydrate carbamazepine as a model drug and two types of surfactant, aliphatic long-chain surfactants and bile salts. Molecular modeling will be used to study the role of crystallographic parameters and molecular structure of dominant crystal faces. The key question is whether nucleation of the stable crystalline phase is enhanced by crystal surfaces of the dissolving metastable phase. If nucleation occurs at very low supersaturations, the drug concentration in solution may never reach the desired levels. The results on the effects of surfactants on nucleation and crystallization will be particularly useful to the pharmaceutical industry and may also have an impact on the manufacturing of specialty chemicals.