正确确定八醇-水分区系数的隐藏核心
Espen Fritschka1,2, Gabriele Sadowski1,2
1TU Dortmund University, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Straße 70, D-44227 Dortmund, Germany.
Molecular pharmaceutics
|July 3, 2025
概括
实验中的醇-水分区系数 (K_OW) 数据分散,特别是对于弱酸/弱,通过一种新的基于pH的外推方法来减少. 这种方法提高了制药开发和环境影响评估的准确性.
科学领域:
- 物理化学 物理化学
- 制药科学 制药科学
- 环境科学环境科学
背景情况:
- 八醇-水分区系数 (K_OW) 对于评估物质分布,环境影响和制药发展至关重要.
- 现有的K_OW测定实验方法产生了显著的数据分散,特别是在弱酸和弱 (95%的API) 等可电离化合物.
- 这种变化使监管部门的批准和使用K_OW作为输入的预测模型 (例如机器学习) 的可靠性变得复杂.
研究的目的:
- 为了研究实验确定K_OW值的广泛分散背后的物理原因.
- 提出和验证一种用于评估分区系数数据的新方法,以尽量减少不确定性.
- 提高药品活性成分 (API) 和其他化学品的K_OW测量的可靠性和一致性.
主要方法:
- 使用物理化学定律分析实验K_OW数据散射.
- 开发一种新的数据评估方法,包括将分布系数与pH相提取,而不是度.
- 结果与来自热力学建模的理论值进行比较,以解释溶液电离.
主要成果:
- 这项研究确定了超算到零溶解物度作为K_OW数据分散的主要原因,而不是分析不确定性.
- 拟议的基于pH的取值方法显著降低了K_OW值的变化,将范围从大约2.4缩小到0.5对数单位.
- 新方法与现有的实验度分析技术兼容,并产生与理论预测一致的结果.
结论:
- 一种基于pH的新型抽取方法提供了一种更准确和可靠的方法来确定K_OW值,特别是对于可电离物质.
- 这种方法解决了K_OW数据中的关键不一致性,提高了其对药物开发,监管过程和预测建模的有用性.
- 经过验证的方法为基于分区行为的更强大的环境和人类健康风险评估提供了途径.
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