Solubility of sparingly-soluble ionizable drugs
- 作者：Alex Avdeef
- 关键词：Sparingly-soluble ionizable compounds ; pH-dependent solubility ; Solubility equations ; Aggregation ; Complexation ; Shake-flask method ; Miniaturized shake-flask method ; Dissolution template titration method ; Micro dissolution method
- 刊名：Advanced Drug Delivery Reviews
- 出版年：2007
- 期刊代码：2_0169409x
- 类别：bio
- 出版时间：30 July 2007
- 卷：59
- 期：7
- 页码：568-590
- 文件大小：2321 K
摘要
The experimental and computational basis of the pH-dependent measurement of solubility of sparingly-soluble ionizable drugs is reviewed. Recently described compound-sparing (but still accurate) approaches, suitable for application in preclinical development, and appropriate for the analysis of solubility of “problematic” molecules, are critically examined. A number of useful experimental methods are reviewed, including the miniaturized shake-flask microtitre plate, the micro solubility self-calibrating direct UV, potentiometric, and the micro dissolution methods. Several molecules were selected as case studies to illustrate important concepts, with re-analysis of literature data using recently established computational tools.