Solubility of sparingly-soluble ionizable drugs

Adv Drug Deliv Rev. 2007 Jul 30;59(7):568-90. doi: 10.1016/j.addr.2007.05.008. Epub 2007 May 29.


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.

Publication types

  • Review

MeSH terms

  • Chemical Phenomena
  • Chemistry, Pharmaceutical
  • Chemistry, Physical
  • Excipients / chemistry
  • Hydrogen-Ion Concentration
  • Ions / chemistry
  • Pharmaceutical Preparations / chemistry
  • Pharmacokinetics*
  • Potentiometry
  • Solubility


  • Excipients
  • Ions
  • Pharmaceutical Preparations