F. Reymond et al., Ionic partition diagrams of ionisable drugs: pH-lipophilicity profiles, transfer mechanisms and charge effects on solvation, J ELEC CHEM, 462(2), 1999, pp. 235-250
The transfer of a series of weak acids, bases and ampholytes has been studi
ed by cyclic voltammetry at the water \ 1,2-dichloroethane interface in ord
er to determine their lipophilicity. Physicochemical parameters such as the
standard Gibbs energy of transfer and the standard partition coefficients
of the ionised forms I of these compounds (log P-I(0')) were measured as a
function of aqueous pH, and the dissociation constants in the organic phase
were deduced from these data. The results obtained are presented in the fo
rm of ionic partition diagrams which define the domains of predominance of
all the species present in both phases. This representation affords both a
precise description of the mechanisms governing the transfer from one phase
to the other, and a reliable assessment of pH lipophilicity profiles. The
various partition coefficients are compared to evaluate qualitatively the l
ipophilicity of each species, and the differences between the partition coe
fficients of the charged and the neutral form of a compound are interpreted
in terms of their chemical structure, showing an increase in organic phase
affinity for ions with intramolecular charge stabilisation. This study dem
onstrates also that both charged and neutral species can penetrate into the
organic phase and shows the importance of the passive transfer of organic
ions for drug disposition and pharmacokinetics. (C) 1999 Elsevier Science S
.A. All rights reserved.