无形固体分散物的溶解,相位行为和质量运输在吸收的人类肠液中
Ahmed Elkhabaz1, Dana E Moseson1, Joachim Brouwers2
1Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA.
无形固体分散 (ASD) 通过形成超和溶液来增强药物的生物可用性. 这项研究观察到在ASD释放在肠道液体中的无形纳米滴,改善药物扩散.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 物理化学 物理化学
背景情况:
- 无形固体分散剂 (ASDs) 通过增强溶解和超和,提高难溶性药物的口服生物可用性.
- 了解ASD的内行为对于预测体内表现至关重要.
研究的目的:
- 为了研究无形固体分散 (ASDs) 的内行为,使用可溶性差的药物,具有不同的结晶倾向.
- 在模拟和吸入的肠液中,在ASD释放过程中描述超和纳米滴形成的概况.
主要方法:
- 准备的无形固体分散剂 (ASDs) 的阿塔萨纳维尔和波萨可纳在10%的药物负载与基甲基纤维素乙烯酸酸盐 (HPMCAS).
- 在吸入的快速状态人类肠液 (FaHIF) 和复合快速状态模拟肠液 (复合FaSSIF) 中评估药物释放和超和.
- 使用显微镜特征无形纳米滴形成和分析药物结晶动力学.
主要成果:
- 阿扎纳维尔ASD显示完全释放和持续高流量,而波萨可纳ASD由于结晶而显示度和流量下降.
- 球形无形纳米滴 (100-150nm) 在ex vivo FaHIF中形成,对于两个ASD,最大限度地扩散流量.
- 在模拟液体中观察到的纳米滴形成和结晶等现象也存在于吸入的光液中.
结论:
- 无形纳米滴形成是最大化在超和窗口期间从ASD扩散流的关键机制.
- 缓冲容量差异影响模拟和吸入肠液之间的ASD释放率.
- 模拟液体中ASD的内现象准确地反映了它们在吸入的肠液中的行为.
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