Solubilization of monovalent weak electrolytes by micellization or complexation.
In order to prepare a liquid formulation for a weak electrolyte, micellization or complexation is often applied with the solution pH controlled to have some of the drug molecules ionized. The efficiency of the micellization is evaluated by either the micellar solubilization capacities, kappau, and kappai or the micellar partition coefficients, Ku(m) and Ki(m), for the unionized and ionized drug species. Similarly, the efficiency of complexation is evaluated by either the complex solubilization capacities, tauu and taui or the drug-ligand binding constants,Ku(1:1) and Ki(1:1). In this study, the experimental values of these descriptors were generated for seven ionizable drugs. The relationships of the logarithms of each descriptor to the logarithm of the octanol-water partition coefficient of the unionized drug (log Pu) and ionized drug species (log Pi) were evaluated. Although kappa and tau cannot be predicted, this study shows that Km and K1:1 are dependent on log P for both the unionized and ionized drug species. Thus, the total drug solubility for a weak electrolyte solubilized by micellization or complexation can be predicted at any pH.
He
Yan
Y
College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA. yhe@rdg.boehringer-ingelheim.com
Yalkowsky
Samuel H
SH
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004573:Electrolytes / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
D004573:Electrolytes; D008024:Ligands; D008823:Micelles; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin