选有机小分子辅助物在基于可变性和结合分析的三极体固体分散物:实验和分子模拟
Sidian Zhang1, Huaqi Wang1, Xiuying Zhao1
1State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
AAPS PharmSciTech
|January 24, 2024
概括
将托等有机分子添加到固体分散剂中,显著提高了药物的溶解性. 这种方法通过优化药物配方中的分子间相互作用来增强药物输送.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 计算化学的计算化学
背景情况:
- 改善难溶性药物的水溶性对于有效的药物输送至关重要.
- 固体分散与聚合物增强药物溶解性,但进一步优化是可能的.
- 纳入有机小分子可以调节固体分散中的分子间结.
研究的目的:
- 确定一种最佳的有机小分子辅助剂,以增强在聚烯利胺固体分散中的卡巴马西平溶解度.
- 研究分子间结在药物溶解性增强中的作用.
- 通过实验性准备和固体分散的表征来验证计算预测.
主要方法:
- 量子力学模拟用于计算药物辅助剂相互作用的键参数和吉布斯自由能量.
- 分子动力学模拟用于分析二进制和三进制系统中的药物迁移.
- 使用卡巴马泽,聚烯和精选的有机小分子制备和表征固体分散物.
- 准备好的固体分散物的可溶性测试.
主要成果:
- 根据可溶性参数选了13种有机小分子.
- 由于与卡巴马泽的有利结相互作用,托芬被计算确定为最佳的第三成分.
- 分子动力学模拟支持三元系统中药物的增强流动性.
- 实验结果证实,托芬显著改善了卡巴马西平的溶解性,与模拟预测一致.
结论:
- 添加特定的有机小分子,特别是托,有效地提高了固体分散中的药物溶解性.
- 基于分子间相互作用和可溶性参数的计算选是选择最佳辅助剂的可行策略.
- 这种方法为设计改进的药物配方和未来的临床研究提供了理论指导.
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