通过计算即服务和实验验证,对药物辅助剂混合性进行系统无关的预测
Georgios S E Antipas1, Regina Reul2, Kristin Voges2
1Molecular Modelling Laboratory, Bahnhofplatz, 6300, Zug, Switzerland. gantipas@mmlpi.ch.
Scientific reports
|July 2, 2024
概括
计算预测准确地确定了用于制药热挤出的表面活性剂-聚合物混合性,减少了对广泛实验的需求. 这种数字双胞胎方法为药物输送系统提供了资源高效的稳定性评估.
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:
- 热挤出 (HME) 是制药制造中的一个关键工艺,用于制造固体分散.
- 预测表面活性剂和聚合物的可混合性对于稳定的无形固体分散 (ASD) 至关重要.
- 对混合性的实验选可能是耗时和资源密集的.
研究的目的:
- 应用计算即服务来预测制药表面活性剂 (维生素E TPGS,Tween 80) 与Copovidone VA64聚合物的混合性.
- 建立计算方法作为HME过程中的实验性混合性测试的数字双胞胎.
- 在ASD中确定活性药物成分/辅助剂混合物的关键稳定点.
主要方法:
- 用于分子动力学和自由能量扰动计算,利用了一个大规模并行架构.
- 在180°C的摩拉基布斯自由能量概况上确定了双极,旋极和机械混合的临界点.
- 执行无人监督的,系统不可知混合性预测.
主要成果:
- 在计算的混合度极限 (维生素ETPGS的9.0重%,Tween 80的10.0重%) 和实验值 (分别为7重%和9重%) 之间达成了密切一致.
- 为每个表面活性剂-聚合物系统确定了不同的破坏稳定机制.
- 验证了计算方法来预测HME相关温度下的表面活性剂-聚合物混合性.
结论:
- 计算稳定性预测作为实验查的物理意义,资源效率高的数字双胞胎.
- 这种方法对于优化ASD配方和预测关键稳定点有价值.
- 该方法支持通过准确的混合性评估开发先进的药物输送系统.
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