Alsenz Jochem, Kansy Manfred
Preclinical Research, Pharma Division, F. Hoffmann-La Roche Ltd., CH-4002 Basle, Switzerland.
Adv Drug Deliv Rev. 2007 Jul 30;59(7):546-67. doi: 10.1016/j.addr.2007.05.007. Epub 2007 May 29.
Measurement of drug solubility in various solvents is one of the key elements of compound characterization during the whole discovery and development process. This review summarizes current experimental approaches and addresses recent advances in the experimental methods used to determine drug solubility in drug discovery and early development. This paper focuses on high throughput methods designed to determine kinetic and thermodynamic (equilibrium) solubility but traditional methods are also presented. The focus, positioning, experimental setup, pros and cons, and limitations of individual assays are discussed and differences in solubility studies in discovery and development environments are highlighted. Finally, future needs and trends in solubility assay development designed to overcome current bottlenecks and trade-offs between speed and quality/quantity of measurements are addressed.
在整个药物发现和开发过程中，测量药物在各种溶剂中的溶解度是化合物表征的关键要素之一。本综述总结了当前的实验方法，并阐述了在药物发现和早期开发中用于测定药物溶解度的实验方法的最新进展。本文重点关注旨在测定动力学和热力学（平衡）溶解度的高通量方法，但也介绍了传统方法。讨论了各个分析方法的重点、定位、实验设置、优缺点和局限性，并突出了在发现和开发环境中溶解度研究的差异。最后，探讨了溶解度分析方法开发的未来需求和趋势，旨在克服当前的瓶颈以及测量速度与质量/数量之间的权衡。
