Probing the permeation enhancement of mefenamic acid by ethanol across full-thickness skin, heat-separated epidermal membrane and heat-separated dermal membrane.

The permeation enhancement of mefenamic acid by ethanol across full-thickness porcine skin, heat-separated epidermal membrane and heat-separated dermal membrane has been probed. Three donor phases saturated with mefenamic acid were used: (1) PEG400; (2) PEG400 with 10% ethanol; (3) mefenamic acid in PEG 400 with 30 mg ml(-1) cetrimide; these were applied to membranes mounted in Franz diffusion-type cells with 30 mg ml(-1) cetrimide as receptor phase (n > or =5). Across full-thickness skin, the flux was below the limit of detection from PEG400, but with the inclusion of 10% ethanol was 0.83 microg cm(-2)h(-1). When cetrimide was present in the donor (and receptor) phase the flux was very low 0.1 microg cm(-2)h(-1). Across heat-separated epidermal membrane the flux from PEG was 11.9+/-2.4 microg cm(-2)h(-1) with a 2.42 x increase in flux observed when 10% ethanol was present (p=0.0095). Across heat-separated dermal membrane the flux from PEG400 was 0.62+/-0.13 microg cm(-2)h(-1), with a 2.34 x increase in flux observed when 10% ethanol was present (p=0.0027). To conclude, complexation and co-permeation with ethanol via a pull effect was confirmed as the mechanism of enhanced skin permeation of mefenamic acid. Full thickness skin provides a more effective barrier than either isolated dermis or epidermis, casting doubt over the use of heat-separated epidermal membranes to model skin permeation and penetration. There was evidence that cetrimide does not cause skin barrier modulation, supporting its use as an effective receptor phase.