Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions.
Capillary electrophoresis (CE) was evaluated as an in-vitro format for experimental modelling of membrane permeability using only nanogram quantities of drug compounds. The rationale for the CE technique emanates from emulation of a lipid-like pseudo-stationary phase that governs separations mainly as a result of differences in molecular size, lipophilicity, hydrogen bonding and charge, all of which also have a strong influence on in-vivo drug absorption. By means of micellar, microemulsion and liposome electrolytes, the migration behaviour was studied at 37 degrees C for 22 model drug compounds. The generated CE retention factor data were then compared with membrane permeability reference data. Both simple log D and more common Caco-2 cell parameters were evaluated. In addition, permeation through intestinal segments of rat ileum and rat colon was included. An improved correlation was obtained in the order: micellar < microemulsion < liposome systems. Although the correlation for the best liposome CE system was only R(2)=0.77, the evaluation results for all emphasized the strength and flexibility of CE for assessing specific drug-membrane interaction through tailor-made lipophilic media.
Ornskov
Eivor
E
Pharmaceutical and Analytical R and D, AstraZeneca R and D Mölndal, SE-431 83 Mölndal, Sweden. eivor.ornskov@astrazeneca.com
Gottfries
Johan
J
Erickson
Magnus
M
Folestad
Staffan
S
D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D003106:Colon / Q000737:chemistry / Q000378:metabolism; D019075:Electrophoresis, Capillary / Q000379:methods*; D004655:Emulsions; D006801:Humans; D007082:Ileum / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes; D008823:Micelles; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics
D004655:Emulsions; D008081:Liposomes; D008823:Micelles; D004364:Pharmaceutical Preparations