无形固体分散中的药物-聚合物相互作用和分子混合性:键-捐赠组的二元性
Lennert Cools1,2, Elien Derveaux2, Felien Reniers3
1Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, Leuven 3000, Belgium.
Molecular pharmaceutics
|March 12, 2026
概括
键显著影响无形固体分散 (ASDs). 这项研究表明,在使用Eudragit S100的自闭症患者中,药物聚合物的混合性取决于药物.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 无形固体分散 (ASD) 对于提高药物的溶解性和生物可用性至关重要.
- 键 (H键) 在ASD稳定性和药物释放中起着至关重要的作用,但预测其对相位行为的影响是具有挑战性的.
- 了解药物聚合物相互作用是设计有效的ASD配方的关键.
研究的目的:
- 为了研究diflunisal (DIF) 和其同类物与Eudragit S100 (ES100) 的混合性和H键相互作用.
- 阐明H键供体和受体组在ASD中药物聚合物相互作用中的作用.
- 为了比较基于ES100的ASD中的H结合与之前研究的基于聚乙烯酸乙烯酸 (PVPVA) 的ASD.
主要方法:
- 使用喷雾干燥技术制备ASD.
- 固态核磁共振 (ssNMR) 放松计用于分子混合性评估.
- 13C-CPMAS ssNMR光谱法用于评估药物和聚合物之间的H键相互作用.
主要成果:
- 在所有ASD中观察到均质的混合,这是由于ES100碳素基和DIF衍生物的碳基之间的H键相互作用.
- 原生DIF和DIF甲基的较低的最大药物负载被归因于分子间和分子内H键之间的竞争.
- 在基于ES100的ASD中,API H-债券接受组的可用性对于混合性至关重要,与基于PVPVA的ASD不同,API H-债券捐赠组至关重要.
结论:
- 键相互作用的性质,特别是药物的受体组的可用性,决定了ASD与具有键供体和受体功能的聚合物的混合性.
- 预测ASD阶段行为需要考虑药物结构,聚合物特性和竞争性H键相互作用之间的相互作用.
- 这项研究通过有针对性的H键工程控制药物聚合物混合性,提供了对自闭症的合理设计的见解.
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