改性释放产品的模型支持的溶解方法:肠膜涂层与延长释放烯片.
Mauricio A García1, Jozef Al-Gousous2, Pablo M González3
1Departamento de Farmacia, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, 7820436, Chile.
International journal of pharmaceutics
|March 28, 2025
概括
延长释放 (XR) 基托的溶解测试需要高缓冲度以获得准确的体外生物预测结果. 低度缓冲器不能完全捕捉XR剂型在体内增强的缓冲器容量.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 物理化学 物理化学
背景情况:
- 药物产品开发面临挑战,溶解测试对于预测体内性能至关重要.
- 溶性较差的电离药物由于有效pKa (pKa,eff) 的降低,在生物相关的二碳酸盐缓冲中溶解得更慢.
- 这种效果可能不同于控制释放配方,如肠涂层 (EC) 和延长释放 (XR) 剂型.
研究的目的:
- 为了研究和比较内涂层 (EC) 和延长释放 (XR) 烯配方的体外溶解概况.
- 评估在模仿肠道状况的低度缓冲器中获得的体外溶解数据的生物相关性.
- 阐明配方类型和缓冲条件对药物溶解和体内性能的影响.
主要方法:
- 在低度缓冲器中EC和XR烯配方的体外溶解研究.
- 在体内比较生物利用性研究以确认生物相关性.
- 质量/电荷平衡建模以获得关于溶解行为的机械洞察力.
主要成果:
- 在体外溶解和体内吸收EC片的EC片受到涂层聚合物材料的影响.
- 在XR配方的体外溶解显示了低度介质的配方依赖差异,这些差异在体内没有观察到.
- 机械建模表明,XR剂型在体内表现出增强的缓冲容量,这是由于扩散速度较慢和高的液体对固体比率,而在体外介质中低度并没有复制.
结论:
- 在低度缓冲器中进行溶解测试可能无法准确预测XR烯配方的体内性能.
- 建议在高缓冲度进行溶解实验,以提高XR剂型的生物预测性.
- 了解配方设计,缓冲条件和溶解机制之间的相互作用是成功开发药物产品的关键.
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