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

控制药物化合物溶解过程中结晶的分子模拟方法

• 批准号: 9526328
• 负责人: Nair Rodriguez-Hornedo
• 金额: $ 16.5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9526328&HistoricalAwards=false
• 关键词: Molecular; Simulation; Approach; Control; Crystallization

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.

CTS - 9526328 密歇根大学 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。 目标包括确定亚稳固相的作用，稳定的分子晶体的成核和解释的成核机制和晶体形态的表面活性剂协会的影响。 将使用二水合物卡马西平作为模型药物和两种类型的表面活性剂（脂肪族长链表面活性剂和胆汁盐）进行实验。 分子模拟将用于研究晶体学参数和主要晶面的分子结构的作用。 关键问题是溶解的亚稳相的晶体表面是否增强了稳定结晶相的成核。 如果成核在非常低的过饱和度下发生，则溶液中的药物浓度可能永远不会达到期望的水平。 关于表面活性剂对成核和结晶的影响的结果将对制药工业特别有用，并且也可能对特种化学品的制造产生影响。