The Dyrssen [1] dual-phase Potentiometrie titration method for measuring the oil-water partition coefficient, log P, has undergone considerable recent development [2-9]. The robust pH-metric technique can be used to determine the ionization constants (pKa) and the partition constants (log P and log Ke, the ion-pair extraction constant [10]) of ionizable drug substances. The present review will focus on how these equilibrium constants are used to calculate the lipophilicity profile, which is a plot of the apparent partition coefficient, that is, the log of the distribution function, log D, vs pH. The mathematical basis of the fully generalized distribution function (applicable to multiprotic substances or substances which undergo aggregation or complexation reactions), the experimental design and limitations of the Dyrssen technique, the effect of salt on lipophilicity, the relationship between the aqueous pH scale and the pH scale in the lipid phase, the distinctions between micro- and wacroconstant-based calculations of the lipophilicity profile will be considered. Applications to a variety of pharmaceutically interesting compounds, both lipophilic and hydrophilic, will be presented.

0 0

Post a comment