在生理双碳酸盐缓冲中溶解与溶解的可溶性
Felix Claussen1, Jozef Al-Gousous1,2, Niloufar Salehi2,3
1Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.
Pharmaceutical research
|May 2, 2024
概括
与二碳酸盐缓冲器相比,酸盐缓冲器显示了溶解性-溶解性不匹配,影响了制药溶解测试. 模拟准确地预测了这些差异,突出了在体内预测中需要考虑缓冲器动力学的必要性.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 计算化学计算化学
背景情况:
- 酸盐缓冲器是药物溶解测试中生理双碳酸盐缓冲器的常见替代品.
- 缓冲特性中的差异使得从酸盐到体内条件的溶解数据的推断变得复杂.
研究的目的:
- 描述可离子化合物的二碳酸盐和酸盐缓冲器之间的溶解性和溶解差异.
- 评估溶解行为的in silico模型的预测准确度.
主要方法:
- 使用可逆非平衡 (RNE) 和穆尼模型进行布洛芬溶解的模拟.
- 在体外实验验证不同剂量的二碳酸盐和酸盐缓冲剂中的溶解.
- 在不同的缓冲系统中分析表面pH和散装pH的关系.
主要成果:
- 在两种缓冲系统之间观察到显著的溶解性与溶解性不匹配.
- 内部模拟准确地预测了这种不匹配.
- 该研究发现,在二碳酸盐中和时,药物表面pH值和散装pH值之间存在很大的差距,但在酸盐中没有.
结论:
- 观察到的差异归因于二碳酸盐缓冲器中不完全的界面反应平衡.
- 泥pH值测量是肠道二碳酸盐缓冲体表面pH值的不可靠指标.
- 精确预测肠道药物溶解需要考虑H2CO3-CO2互转化动力学.
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