以乙醇为基础的可溶性促进口服药物配方开发:考虑可溶性-透性的相互作用
1Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
International journal of pharmaceutics
|February 12, 2024
概括
使用乙醇开发口服药物配方需要平衡药物的溶解性和肠道透性. 使用最小有效乙醇度通过避免不必要的透性降低来最大限度地吸收.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 制定 发展 制定 发展
背景情况:
- 乙醇经常用于口服药物配方,以提高难以溶解的化合物的可溶性.
- 了解乙醇度,药物溶解性和肠道透性之间的复杂相互作用对于成功的配方设计至关重要.
- 碳胺 (CBZ) 是BCSII类抗药物,作为研究这些效应的模型化合物.
研究的目的:
- 研究影响以乙醇为基础的口服药物配方成功的关键因素.
- 评估乙醇对药物的溶解性,肠道透性和溶解的度依赖性影响.
- 在含有乙醇的系统中开发一种可溶性-透性关系的预测模型.
主要方法:
- 在不同度的乙醇中评估卡巴马西平 (CBZ) 的溶解性.
- 评估了在体外Caco-2细胞透性和在体内老鼠 perfusion 研究,以不同的乙醇水平.
- 进行了生物相关的溶解研究,以确定药物完全溶解的最低乙醇度.
- 开发了一种结合乙醇吸收的预测模型来描述溶解度-透度的相互作用.
主要成果:
- 乙醇显著增加了CBZ溶解度,以度依赖的方式.
- 随着乙醇度的增加,同时观察到肠道透率 (体外和体外) 的降低.
- 在考虑乙醇吸收时,在预测和实验透性之间达成了很好的协议.
- 最小的乙醇度 (30-50%) 足以完全溶解低剂量CBZ (1-5毫克) 没有沉.
结论:
- 基于乙醇的配方的成功开发需要仔细考虑药物的溶解性,透性,它们的相互作用以及预期的药物剂量.
- 最优的策略是只使用所需的最小乙醇量来使药物在整个胃肠道中溶解.
- 这种方法旨在减轻不必要的透性损失,并最大限度地提高药物的整体吸收.
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