形态景观对tizanidine共结晶结果的多态和单态的影响
Di Wu1, Lin Fu2, Hongxun Hao3
1National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
International journal of pharmaceutics
|October 26, 2024
概括
分子构造影响共结晶结果,影响药物的溶解性和溶解. 这项研究揭示了形状景观如何决定tizanidine (TZND) 盐的多态性,为晶体工程提供了洞察力.
科学领域:
- 结晶科学 结晶科学
- 制药化学 制药化学 制药化学
- 固态化学 固态化学
背景情况:
- 分子构造对于多态核和共晶形成至关重要.
- 分子构成和共结晶多态性之间的联系仍未得到充分探索.
- 了解这种关系是设计具有改进性质的新固体形式的关键.
研究的目的:
- 为了研究分子形状景观对共结晶结果的影响,使用tizanidine (TZND) 作为模型.
- 探索TZND的新盐形式的形成,并评估它们的物理化学特性.
- 阐明控制TZND共晶体中多态和单态的分子机制.
主要方法:
- 使用四种共同成型物的联合结晶实验 (酸,酸,p-hydroxybenzoic酸,heptanedioic酸).
- 开发和描述TZND的五种新的盐形式.
- 晶体结构分析,构造分析,分子动力学模拟和量子化学计算.
- 研究共结晶核化过程.
主要成果:
- 成功开发了五种新的tizanidine盐形式 (TZND),与TZND相比,它们具有更高的水溶性和溶解率.
- 同结晶的行为与共同形成物有所不同:酸表现出溶剂依赖的多态性,而酸,p-基酸和酸表现出溶剂独立的单态性.
- 形状分析显示了TZND形状在不同的共同结晶结果中存在显著差异.
- 分子模拟表明,溶剂效应和辅助器相互作用决定了主导的TZND形状.
结论:
- 分子结构多样性是控制共结晶多态性的关键因素.
- 溶剂效应和协同形成器相互作用之间的相互作用决定了构造格局和随后的协同结晶结果.
- 提出了一个解释TZND共结晶中的多态和单态的分子机制,为晶体工程提供了宝贵的见解.
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