Solubility of sparingly-soluble ionizable drugs.
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.
Avdeef
Alex
A
pION INC, 5 Constitution Way, Woburn, MA 01801 USA. aavdeef@pion-inc.com
D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010599:Pharmacokinetics; D011199:Potentiometry; D012995:Solubility
D005079:Excipients; D007477:Ions; D004364:Pharmaceutical Preparations