LIPOPHILICITY OF AMPHOTERIC MOLECULES EXPRESSED BY THE TRUE PARTITION-COEFFICIENT

The octanol/water partition coefficients of six amphoteric drugs were investigated. Nitrazepam, albendazole and sulfadimidine are ordinary ampholytes, while pyridoxine, niflumic acid and terbutaline belong to the zwitterionic amphoteric compounds. The pH-partition profile of compounds showed maximum (parabolic) curve. Analyses of the UV spectra in aqueous and octanol phases at different pH values after partitioning equilibrium had been achieved proved the transfer of the neutral species into the octanol phase. The true partition coefficients were calculated from log P-app values using macroprotonation constants for ordinary ampholytes and microprotonation constants in the case of zwitterionic molecules. The results emphasize that only the true partition coefficient closely represents the intrinsic lipophilicity of zwitterionic amphoteric compounds.