在模拟肠道液体中的药物溶解与脂性:充电是否重要?
Teodor Boyanov1, Liliya Vinarova1, Christophe Tistaert2
1Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1164 Sofia, Bulgaria.
Molecular pharmaceutics
|January 23, 2026
概括
药物电离显著影响肠道溶解,影响口服吸收. 这项研究揭示了静电相互作用是充电药物的关键,推进了难溶药物的预测建模.
科学领域:
- 药理动力学 药理动力学
- 药物发现 药物发现 药物发现
- 物理化学 物理化学
背景情况:
- 药物溶解在肠液中对于口服吸收至关重要,并受到食物的影响.
- 基于脂性性的肠道溶解现有模型是有限的,特别是对于电离药物.
- 了解药物电离在脂性-溶解性关系中的作用对于准确的预测至关重要.
研究的目的:
- 扩大数据集并开发一个模型,阐明充电化合物的脂性和溶解之间的联系.
- 调查药物电离对肠道溶解的影响.
- 探索静电相互作用在药物溶解中的作用.
主要方法:
- 确定26种疏水药物的水溶性,八醇-水分区系数 (LogP/D) 和在养状态模拟肠液 (FeSSIF) 中的溶解度.
- 综合实验数据与文献值进行综合分析 (n=198).
- 改变FeSSIF的pH值,以研究中性和充电状态下的药物溶解.
主要成果:
- 在肠道溶解和LogP/D之间发现了良好的整体相关性 (R2=0.74).
- 中性化合物与LogP有很强的相关性 (R2=0.89),但带电化合物与LogD失去了相关性 (R2=0.40).
- 溶解度与中性状态 (R2=0.92) 的LogD有很好的相关性,但在充电状态 (R2=0.02) 则没有.
结论:
- 静电相互作用显著影响了电离药物在肠液中的溶解.
- 阳离子药物呈现出意想不到的低溶解度,而阴离子药物显示出相位分离.
- 这些发现促进了对生物相关介质中药物溶解的理解,支持了改进的预测建模.
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