Immobilized artificial membrane (IAM)-HPLC for partition studies of neutral and ionized acids and bases in comparison with the liposomal partition system

Purpose. To study the partitioning of model acids ((RS)-warfarin and salicy lic acid), and bases (lidocaine, (RS)-propranolol and diazepam), with immob ilized artificial membrane (IAM)-HPLC, as compared to partitioning in the s tandardized phosphatidylcholine liposome/buffer system. Methods. The pH-dependent apparent partition coefficients D were calculated from capacity factors (k(IAM)') obtained by IAM-HPLC, using a 11-carboxylu ndecylphosphocholine column. For lipophilic compounds k(IAM)', values were determined with organic modifiers and extrapolation to 100% water phase (k( IAMw)') was optimized. Temperature dependence was explored (23 to 45 degree s C), and Gibbs free energy (Delta G), partial molar enthalpy (Delta H) and change in entropy (Delta S) were calculated. Equilibrium dialysis was used for the partitioning studies with the liposome/buffer system. Results. For extrapolation of k(IAMw)', linear plots were obtained both wit h the respective dielectric constants and the mole fractions of the organic modifier. All tested compounds showed a similar pH-D diagram in both syste ms; however, significant differences were reproducibly found in the pH rang e of 5 to 8. In all cases, Delta G and Delta H were negative, whereas Delta S values were negative for acids and positive for bases. Conclusions. In both partitioning systems, D values decreased significantly with the change from the neutral to the charged ionization state of the so lute. The differences found under physiological conditions, i.e. around pH 7.4, were attributed to nonspecific interactions of the drug with the silic a surface of the IAM column.