Determination of liposome-buffer distribution coefficients of charged drugs by capillary electrophoresis frontal analysis.
The potential of using CE frontal analysis (CE-FA) to study the interactions between a range of charged low molecular weight drug substances and liposomes was evaluated. The liposomes used were net negatively charged and consisted of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphate monosodium salt in a ratio of 80/20 mol%. Apparent distribution coefficients (D(mem)), defined as the molar concentration of drug substance in the membrane phase divided by the molar concentration of drug substance in the aqueous phase, were successfully determined for six positively and eight negatively charged drug substances with log D(mem) ranging from 1.35 to 3.63. The extent of liposome-buffer distribution was found to be dependent on the drug concentration. The results obtained with the developed CE-FA method were in good agreement with results obtained by equilibrium dialysis. Furthermore, the CE-FA method was faster, less labor intensive and required smaller sample volumes (approximately 50 microL) compared with equilibrium dialysis. Thus, CE-FA is an efficient and useful tool for the characterization of interactions between liposomes and low molecular weight drug substances.
Franzen
Ulrik
U
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jorgensen
Lene
L
Larsen
Claus
C
Heegaard
Niels H H
NH
Østergaard
Jesper
J
D002021:Buffers; D055598:Chemical Phenomena; D019075:Electrophoresis, Capillary / Q000379:methods*; D016014:Linear Models; D008081:Liposomes / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry
D002021:Buffers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D011433:Propranolol