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探索使用经过修改的体外消化试验来评估含有里托纳维尔的固体脂基配方
Ioannis I Andreadis1, Arne Schulzen2, Julian Quodbach3
1Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, Sweden; Laboratory of Pharmaceutical Technology, Department of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, Greece.
概括
经过修改的体外消化试验比经典试验更好地预测固体脂基配方 (sLBF) 的性能. 这些改进的方法为临床前药物开发提供了关键的见解,有助于为体内研究选择有效的配方.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 生物制药生物制药公司
背景情况:
- 基于固体脂质的配方 (sLBFs) 提高了难以溶解药物的口服生物可用性.
- 目前的体外脂解分析试验往往无法预测体内LBF的性能.
- 需要改进体外模型来进行sLBFs的临床前评估.
研究的目的:
- 评估三种体外消化试验的适用性,以评估sLBFs.
- 为了比较经典与改性胃肠道消化模型的预测能力.
- 确定测试设计对评估药物溶解和透性的影响.
主要方法:
- 一个经典的一步性肠道消化试验的评估.
- 一个两步的胃肠道消化试验的评估.
- 使用双分区测定法 (Licithin in Dodecane - LiDo) 进行同时的消化和透监测.
- 准备和测试三种sLBFs (M1-M3) 用利托纳维尔作为模型药物.
主要成果:
- 所有测试表明,M1配方在药物溶解中表现最好,而M3表现不佳.
- 经典试验与修改试验相比,提供了不清楚的配方排名.
- 修改后的测试提供了关于胃功率和药物肠道流量的额外数据.
结论:
- 经过修改的体外消化试验为sLBF评估提供了更多生理相关的数据.
- 这些先进的测试提高了对sLBF表现的排名和预测体内结果的能力.
- LiDo和两步测试是关于sLBFs的明智的临床前开发决策的宝贵工具.
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