亚齐尔沙坦晶体的不同溶解分子通路具有不同的形状,由In Situ原子力显微镜显示
Shuhong Song1, Lei Wang1, Guanying Xie1
1State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.
The journal of physical chemistry letters
|September 6, 2023
概括
这项研究揭示了阿齐尔沙坦晶体如何在水和聚乙烯甘醇溶液中溶解,使用原子力显微镜. 阿齐尔沙坦异醇溶液直接溶解,而阿齐尔沙坦I型溶解被聚乙烯甘醇增强.
科学领域:
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
- 晶体学 晶体学是指结晶学.
背景情况:
- 了解药物晶体溶解对于制药配方和生物可用性至关重要.
- 阿齐尔沙坦是一种用于治疗高血压的 ангиотензинII受体抑制剂.
- 添加剂 (如聚乙烯糖醇) 对药物溶解机制的影响尚未完全阐明.
研究的目的:
- 为了研究两个阿齐尔沙坦晶体形式 (异醇溶酸盐和形式I) 在含有聚乙烯甘醇的水溶液中的溶解行为和分子途径.
- 阐明聚乙烯糖醇度对阿齐尔沙坦晶体溶解动力学和机制的作用.
主要方法:
- 使用现场原子力显微镜 (AFM) 来实时观察溶解过程.
- 分析晶体面溶解模式,包括步骤退缩和蚀刻坑的形成.
- 量化蚀刻速率作为聚乙烯糖醇度的函数.
主要成果:
- 亚齐尔沙坦异醇溶酸盐和I型都表现出它们的面部 (100) 的步骤退缩和蚀刻坑形成.
- 蚀刻速度随着聚乙烯糖醇度的增加而增加.
- 阿齐尔沙坦异醇溶液通过直接分子分离溶解,这种机制不受聚乙烯糖醇的影响.
- 阿齐尔沙坦I型溶解涉及表面扩散,用聚乙烯甘醇 (PEG) 促进分子脱离步骤前线.
结论:
- 阿齐尔沙坦异醇溶酸盐和I形式的溶解机制显著不同.
- 聚乙烯甘醇 (PEG) 通过促进分子脱离,作为阿齐尔沙坦I型的溶解增强剂.
- 这些发现提供了对结晶结构依赖的溶解行为和助剂在药物开发中的影响的见解.
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