无形固体分散体的体外溶解/透工具生物可用性预测II:比较和机制性见解
Patrícia D Nunes1, Ana Filipa Ferreira2, João F Pinto3
1R&D Analytical Development, Hovione Farmaciência S.A., Campus do Lumiar, Building S, 1649-038 Lisboa, Portugal; R&D Oral Drug Product Development, Hovione Farmaciência S.A., Campus do Lumiar, Building S, 1649-038 Lisboa, Portugal; Research Institute for Medicines (iMed.Ulisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
概括
两种体外溶解-透 (D/P) 设置进行了比较,以对无形固体分散 (ASD) 进行排名. 微透析的PermeaLoopTM与BioFLUXTM相比,与体内药物吸收的相关性更好,提供了机理性的见解.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药理动力学 药理动力学
背景情况:
- 复杂的配方需要体外方法来预测体外性能和药物释放机制.
- 在体外溶解-透 (D/P) 方法对于在早期开发过程中对药物配方进行排名至关重要.
- 了解药物吸收需要评估溶解和透之间的相互作用.
研究的目的:
- 评估两个无细胞的体外D/P设置,BioFLUXTM和PermeaLoopTM,用于评估伊特拉科纳 (ITZ) -HPMCAS无形固体分散 (ASD).
- 为了比较体外D/P结果与体外的药理动力学数据,用于配方排名的狗模型.
- 使用先进的体外技术,阐明自闭症的药物释放和透机制.
主要方法:
- 应用BioFLUXTM和PermeaLoopTM体外D/P系统,采用溶剂转移方法 (胃到肠道模拟).
- 将PermeaLoopTM与微透析采样集成,以实时分离自由药物,结合菌根的药物和结合体的药物.
- 在狗模型中并行进行体内药理动力学研究,以评估药物吸收.
主要成果:
- 两种D/P系统都提供了类似的ASD质量排名.
- 透LoopTM的透流量与体内AUC有很强的相关性 (R2 ≈ 0.98),表现优于预测差异的BioFLUXTM.
- 通过微透析的PermeaLoopTM确定了自由药物作为透驱动器和富含药物的合物作为保持药物可用性的储存库.
结论:
- 由于其标准化性质,BioFLUXTM适合在早期发育中的ASD初始排名.
- 与微透析相结合的PermeaLoopTM提供了溶解-透的机制理解,这对于微调和在体内测试前选择领先的ASD候选者至关重要.
- 这项研究强调了先进的体外模型对于准确预测体内药物吸收的重要性,从复杂的配方如ASDs.
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