title: pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs.
abstract: OBJECTIVE
  To investigate a novel approach for the determination of liposomal 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 dioleylphosphatidylcholine (DOPC) unilamellar vesicles in 0.15 M KCl at 25 degrees C. The DOPC unilamellar vesicle suspension was prepared via an extrusion process.
  
  
  RESULTS
  The liposomal membrane-water partition coefficients of eight ionizable drugs: ibuprofen, diclofenac, 5-phenylvaleric acid, warfarin, 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 membrane-water partition coefficients as derived from the pH-metric technique are consistent with those obtained from alternative methods such as ultrafiltration and dialysis. It was found that in liposome system, partitioning of the ionized species is significant and is influenced by electrostatic interaction with the membranes. We have demonstrated that the pH-metric technique is an efficient and accurate way to determine the liposomal membrane-water partition coefficients of ionizable substances.
authors.affiliation: pION Inc., Cambridge, Massachusetts 02138, USA.
authors.forename: A
authors.initials: A
authors.lastname: Avdeef
authors.forename: K J
authors.initials: KJ
authors.lastname: Box
authors.forename: J E
authors.initials: JE
authors.lastname: Comer
authors.forename: C
authors.initials: C
authors.lastname: Hibbert
authors.forename: K Y
authors.initials: KY
authors.lastname: Tam
mesh_terms: D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008567:Membranes, Artificial; D010599:Pharmacokinetics; D014867:Water
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008567:Membranes, Artificial; D014867:Water