Influence of counter ions on the skin permeation of methotrexate from water-oil microemulsions

The influence on the permeation of methotrexate across intact hairless mouse skin of different counter ions added to water-oil (w/o) microemulsions containing lecithin, as surfactant, and water-propylene glycol at different pH values, as internal phase, was studied. As counter ions, monooctyl phosphate, monodecyl phosphate, monodecyl glycerophosphate, taurodeoxycholate, dodecyl sulfate and dioctyl sulfosuccinate were used. At pH 4.0, the transport of methotrexate was enhanced by the counter ions and a marked increase in the flux of the drug was measured when dodecyl sulfate and dioctyl sulfosuccinate were used. At pH 5.0 only a slight increase of the flux was observed. The increased permeation was attributed to the lipophilization of methotrexate as a consequence of ion pair formation.