title: Determination of liposome partitioning of ionizable drugs by titration.
abstract: Drug partitioning to liposomes has been suggested as a model for partitioning to biomembranes but has been lacking a rapid analytical assay useful for drug screening. A fast pH-metric titration method for the determination of liposome partitioning of ionizable drugs using small unilamellar phosphatidylcholine vesicles prepared by sonic homogenization has been successfully developed, enabling the use of high lipid-to-drug ratios. Liposome-water partition coefficients of diclofenac and propranolol were determined to study the impact of varying titration parameters, temperature, equilibration time, lipid, and liposome types on the partitioning. To validate this method, the results were compared to literature values generated with different techniques and to pH-metric titration results with large unilamellar vesicles. The rapid pH-metric assay gave liposome partitioning data for the two model compounds which were consistent with other analytical techniques and liposome types.
authors.affiliation: Lilly Forschung GmbH, Pharmaceutical Product Development, Wiesingerweg 25, D-20253 Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Balon
authors.forename: B U
authors.initials: BU
authors.lastname: Riebesehl
authors.forename: B W
authors.initials: BW
authors.lastname: Müller
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004008:Diclofenac / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008567:Membranes, Artificial; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry; D015203:Reproducibility of Results; D012995:Solubility; D013696:Temperature
chemical_list: D008081:Liposomes; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D004008:Diclofenac; D011433:Propranolol