Action of penetration enhancers on human skin as assessed by the permeation of model drugs 5-fluorouracil and estradiol. I. Infinite dose technique.

We have conducted permeation studies to assess the effectiveness of accelerants Azone, oleic acid (OA), decylmethyl sulfoxide (DCMS) and propylene glycol (PG) in promoting the absorption through human skin of model drugs 5-fluorouracil (5FU) and estradiol (ES). Drug permeation from saturated aqueous solutions was monitored before and after accelerant treatment (applied in aqueous and PG vehicles). With ES, the study was repeated with 50% ethanol/water as donor and receptor phases instead of water. Two percent Azone in PG promoted 5FU absorption by almost 100-fold, but 3% Azone with 0.1% Tween 20 in normal saline demonstrated only an eightfold effect. Five percent OA in PG was moderately successful, but 4% aqueous DCMS enhanced 5FU permeation 35-fold initially, but rapidly fell to fourfold. PG itself was ineffective. The accelerants were much less effective in promoting ES absorption; only 5% OA in PG enhanced steroid permeation by more than tenfold, but this fell with time to threefold due to washout of accelerant (ethanol/water system). The experimental conditions utilized fully hydrated stratum corneum with permeants in saturated solutions; under these already optimized conditions for permeation, accelerants were only marginally effective in enhancing the delivery of the relatively non-polar drug ES. Polar drug delivery, as exemplified by 5FU, could still be increased markedly. Azone was considerably more effective when used in conjunction with PG compared to an aqueous vehicle; thus PG itself may play an accelerating role. The 5FU results indicated that Azone and OA remained in the tissue for a long period, but DCMS was rapidly removed by washout.