PH-METRIC LOGP-10 - DETERMINATION OF LIPOSOMAL MEMBRANE-WATER PARTITION-COEFFICIENTS OF IONIZABLE DRUGS

Purpose. To investigate a novel approach for the determination of lipo somal membrane-water partition coefficients and lipophilicity profiles of ionizable drugs. Methods. The measurements were performed by using a pH-metric technique in a system consisting of dioleylphosphatidylch oline (DOPC) unilamellar vesicles in 0.15 M KCI at 25 degrees C. The D OPC unilamellar vesicle suspension was prepared via an extrusion proce ss. Results. The liposomal membrane-water partition coefficients of ei ght ionizable drugs: ibuprofen, diclofenac, 5-phenylvaleric acid, warf arin, propranolol, lidocaine, tetracaine and procaine were determined and the values for neutral and ionized species were found to be in the ranges of approximately 4.5 to 2.4 and 2.6 to 0.8 logarithmic units, respectively. Conclusions. It has been shown that the liposomal membra ne-water partition coefficients as derived from the pH-metric techniqu e are consistent with those obtained from alternative methods such as ultrafiltration and dialysis. It was found that in liposome system, pa rtitioning of the ionized species is significant and is influenced by electrostatic interaction with the membranes. We have demonstrated tha t the pH-metric technique is an efficient and accurate way to determin e the liposomal membrane-water partition coefficients of ionizable sub stances.