Automated assays for thermodynamic (equilibrium) solubility determination.
Automated assays for thermodynamic (equilibrium) solubility determination.
复制标题
DOI：
10.1016/j.ddtec.2018.04.004
复制
发表时间：
2018-07-01
期刊：
影响因子：
--
通讯作者：
Bergstrom, Christel A S
中科院分区：
文献类型：
--
作者：
Sou, Tomas;Bergstrom, Christel A S
溶解度是候选药物的关键理化性质，在药物发现和开发中都很重要。溶解性差不利于口服给药后的吸收，并且可以以各种方式掩盖生物测定中的化合物活性。因此，理想情况下，应在药物开发过程中尽早确定溶解度负债。随着越来越多的化合物作为潜在的候选药物，自动化热力学溶解度测定的高通量筛选，使大量的化合物的快速评估变得越来越重要。这篇综述讨论了目前最广泛使用的自动化测定热力学溶解度的状态，其次是最近的高通量测量相关的溶解度（如溶解速率和过饱和度）的属性和简要概述的预测计算方法的热力学溶解度在文献中报道。
Solubility is a crucial physicochemical property for drug candidates and is important in both drug discovery and development. Poor solubility is detrimental to absorption after oral administration and can mask compound activity in bioassays in various ways. Hence, solubility liabilities should ideally be identified as early as possible in the drug development process. With the increasing number of compounds as potential drug candidates, automated thermodynamic solubility assays for high throughput screening enabling rapid evaluation of a large number of compounds are becoming increasingly important. This review discusses the current status of the most widely used automated assays for thermodynamic solubility, followed by recent high throughput measurements of properties related to solubility (e.g. dissolution rate and supersaturation) and a brief overview of predictive computational methods for thermodynamic solubility reported in the literature.