Percutaneous penetration enhancement activity of aromatic S,S-dimethyliminosulfuranes

The activity of three series of iminosulfuranes (classes I-III) as potentia l transdermal penetration enhancers was investigated. These dimethyl sulfox ide (DMSO) related compounds were synthesized from activated DMSO by triflu oroacetic anhydride. Structure confirmation was accomplished by H-1 NMR, an d C-13 NMR spectroscopy and elemental analysis prior to in vitro testing. H ydrocortisone (HC) was used as a model drug, and the effect of the iminosul furanes on the penetration of HC through hairless mouse skin was evaluated. All enhancers tested were applied to the skill as saturated suspensions in propylene glycol to ensure their maximum thermodynamic activity. Three com pounds, S,S-dimethyl-N-(4-brornobenzoyl)iminosulfurane (9), S,S-dimethyl-N- (5-nitro-2-pyridyl)iminosulfurane (13), and S,S-dimethyl-N-(4-phenylazaphen yl)iminosulfurane (16) showed statistically significant activity quantitate d by amounts of model drug permeated through the skin in 24 h (Q(24)), and flux values, compared to control (propylene glycol without enhancer). Highe st Q(24) and flux values were obtained for 9. 996.2 +/- 192.5 mu g/cm(2) an d 47.9 +/- 7.5 mu g/cm(2) per h, respectively. All arylsulfonyl substituted compounds showed lower or similar enhancement activity when compared to co ntrol. S,S-dimethyl-N-(benzenesulfonyl)iminosulfurane (1), S,S-dimethyl-N-( 2-methoxycarbonylbenzesulfonyl)iminosulfurane (7). and S,S-dimethyl-N-(4-ch lorobenzenesulfonyl)iminosulfurane (8) decreased the permeation of HC signi ficantly (P < 0.05). It is possible that these agents work as retardants un der these experimental conditions. None of the enhancers tested showed sign ificant skin model drug retention, suggesting that these compounds could be useful for increasing systemic rather than local drug delivery. (C) 1999 P ublished by Elsevier Science B.V. All rights reserved.