无形固体分散的溶解机制:聚合物分子重量的作用和识别新的故障模式
Alexandru Deac1, Chailu Que1, Michelle L Cousineau1
1Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States.
聚乙烯利 (PVP) 的分子量显著影响无形固体分散 (ASD) 的药物释放. 了解这些机制,比如对应性极限 (LoC),是优化药物输送系统的关键.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 从无形固体分散 (ASD) 释放药物是复杂的,并未完全理解,阻碍了优化体内性能.
- 一致性极限 (LoC) 描述了一个药物负载值,在这个值上形成一种无形的富含药物的屏障,阻碍释放,特别是在非沉没条件下.
- 以前的研究确定了药物-聚合物相互作用和药物玻璃过渡温度是影响LoC的因素,但聚合物分子重量的作用仍然未被探索.
研究的目的:
- 调查聚乙烯 (PVP) 分子重量对异形固体分散 (ASD) 的相对度极限 (LoC) 和药物释放的影响.
- 阐明不同PVP分子重量的ASD中LoC背后的故障机制.
主要方法:
- 准备了克洛特里马的无形固体分散剂 (ASD),具有不同分子量级的PVP.
- 进行药物释放研究以确定LoC药物负载.
- 使用光共聚焦显微镜分析ASD/溶液接口和ASD膜在高相对湿度下的相位行为,以确定故障模式.
主要成果:
- 呈现良好的药物释放的ASD在ASD/溶液界面形成了稳定的,富含药物的纳米滴.
- 释放不良归因于两种不同的失效模式,取决于PVP分子量:纳米滴滴聚合 (失效模式I) 或相反 (失效模式II).
结论:
- 聚合物分子重量是影响无形固体分散 (ASDs) 的一致性极限 (LoC) 和药物释放机制的关键因素.
- 识别特定的故障模式,如纳米滴滴聚合或相位逆转,对于提高高药载荷ASD的释放性能至关重要.
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