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

Abstract

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 ≥ 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 μg cm −2 h −1. When cetrimide was present in the donor (and receptor) phase the flux was very low 0.1 μg cm −2 h −1. Across heat-separated epidermal membrane the flux from PEG was 11.9 ± 2.4 μg cm −2 h −1 with a 2.42× 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 μg cm −2 h −1, with a 2.34× 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.