无形固体分散的溶解机制:应用三相图来解释释放行为
Alexandru Deac1, Christian Luebbert2, Qingqing Qi1
1Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
预测从无形固体分散 (ASDs) 中释放药物至关重要. 这项研究使用三元相图来了解药物负载如何影响自闭症,揭示了阻碍药物释放的关键点.
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) 越来越多地用于溶解不良的药物.
- 从ASD中释放的药物是复杂的,通常在较高的药物负载 (DLs) 上显示效率降低.
- 一致性极限 (LoC) 表示释放受阻,但缺乏预测方法.
研究的目的:
- 热力学地描述ASDs在水溶液中的相位行为.
- 用三元相图预测形态变化和LoC.
- 为ASD释放行为提供机制性见解.
主要方法:
- 构建实验和计算三元相图.
- 使用扰乱链统计关联流体理论 (PC-SAFT) 进行计算建模.
- 使用光共聚焦显微镜研究疏水阶段形态.
主要成果:
- 实验和PC-SAFT相图成功预测了形态变化.
- 一个关键点 (平面点) 在相图中与LoC相关联.
- 在较高的DL中相互连接的疏水相被确定为阻碍ASD释放的原因.
结论:
- 三进制相位图是理解ASD相位行为和预测LoC的强大工具.
- 这项研究提供了对ASD释放限制的机制性见解.
- 使用相位图的ASDs的in silico设计显示了药物开发的巨大潜力.
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