对药品无形固体分散的动态稳定性的分子洞察力
Vladislav Aulich1, Jan Ludík1, Michal Fulem1
1Department of Physical Chemistry, University of Chemistry and Technology Prague, Technická 5, CZ-166 28 Prague 6, Praha, Czech Republic. cervinkc@vscht.cz.
Physical chemistry chemical physics : PCCP
|December 23, 2024
概括
计算模拟显示,活性药物成分 (API) 和聚合物之间的特定分子相互作用是设计稳定的无形固体分散的关键,改善药物的溶解性和生物可用性.
科学领域:
- 制药科学 制药科学
- 计算化学计算化学
- 材料科学 材料科学 材料科学
背景情况:
- 晶体活性药物成分 (API) 的水溶性较差限制了它们的生物可用性.
- 有生物相容聚合物的无形固体分散 (ASD) 增强了药物溶解性,并使更广泛的候选药物利用成为可能.
研究的目的:
- 为了计算设计二元固体分散的最佳API-聚合物组合.
- 使用in silico方法研究无形药物配方的分子相互作用,可混合性和稳定性.
主要方法:
- 分子动力学 (MD) 模拟用于跟踪散装系统中的原子级相互作用.
- 对结构,凝聚力,能量兼容性和玻璃化特性进行分析.
- 密度功能理论 (DFT) 和非共价相互作用 (NCI) 分析以映射相互作用强度.
主要成果:
- MD模拟确定了具有有益相互作用的API-聚合物对,增强混合性并防止API再结晶.
- 计算证实了聚烯 (PVP) 是一种强烈的键受体,而布洛芬是有效的键供体.
- 模拟表明卡巴马西平与研究的聚合物辅助剂之间的相互作用有限,与实验溶解性趋势保持一致.
结论:
- 分子相互作用的无分析,特别是非共价相互作用 (NCI),有助于理解和合理设计高效的无形固体分散.
- 计算模型为APIs和聚合物辅助剂的分子行为提供了宝贵的见解,用于开发新药配方.
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