通过古典和非古典途径合理化溶剂对灰色富尔文核的影响
Mariana O Diniz1, Harsh Barua1, Jennifer Cookman1
1SSPC the Research Ireland Centre for Pharmaceuticals, Department of Chemical Sciences, and Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.
Crystal growth & design
|July 8, 2025
概括
溶剂的选择显著影响活性药物成分 (API) 核化. 灰色 (GSF) 在酸 (ACN) 中核化速度最快,在甲醇 (MeOH) 中核化速度最慢,这与溶剂特性和中等尺度集群有关.
科学领域:
- 物理化学 物理化学
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
背景情况:
- 溶剂对活性药物成分 (API) 核的作用对于控制结晶过程至关重要.
- 了解溶剂诱导核化行为有助于预测和管理API多态形式.
- 由于其中等大小和灵活性,灰色 (GSF) 作为研究核化的模型API.
研究的目的:
- 研究不同溶剂对灰色 (GSF) 的核化行为和多态景观的影响.
- 描述甲醇 (MeOH),乙二 (ACN) 和n-丁乙酸 (nBuAc) 中核化的相对容易.
- 为了将核化行为与溶剂特性和溶液结构相关联.
主要方法:
- 进行了2960个诱导时间实验以量化核化速率.
- 利用光谱分析和动态光散射来研究溶液特性.
- 应用了古典核化理论评估和分析了预指数因子.
主要成果:
- GSF在MeOH中结晶为稳定的I形式,并在ACN和nBuAc中结晶为溶解形式.
- 核化容易遵循的顺序是:ACN > nBuAc > MeOH,与界面能量相关.
- 在ACN和nBuAc中观察到中等尺度集群,但不是MeOH,这表明非经典的核化途径.
结论:
- 溶剂的选择深刻影响GSF核化动力学和多态结果.
- 溶液中中尺度集群的存在和特征是非经典核形成的关键因素.
- 结果为通过溶剂选择控制API结晶提供了见解.
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