Determination of liposome partitioning of ionizable drugs by titration

Drug partitioning to liposomes has been suggested as a model for partitioni ng to biomembranes but has been lacking a rapid analytical assay useful for drug screening. A fast pf-l-metric titration method for the determination of liposome partitioning of ionizable drugs using small unilamellar phospha tidylcholine vesicles prepared by sonic homogenization has been successfull y developed, enabling the use of high lipid-to-drug ratios. Liposome-water partition coefficients of diclofenac and propranolol were determined to stu dy the impact of varying titration parameters, temperature, equilibration t ime, lipid, and liposome types on the partitioning. To validate this method , the results were compared to literature values generated with different t echniques and to pH-metric titration results with large unilamellar vesicle s. The rapid pH-metric assay gave liposome partitioning data for the two mo del compounds which were consistent with other analytical techniques and li posome types.