Percutaneous penetration enhancement activity of aromatic S, S-dimethyliminosulfuranes

The activity of three series of iminosulfuranes (classes I-III) as potential transdermal penetration enhancers was investigated. These dimethyl sulfoxide (DMSO) related compounds were synthesized from activated DMSO by trifluoroacetic anhydride. Structure confirmation was accomplished by 1H NMR, and 13C NMR spectroscopy and elemental analysis prior to in vitro testing. Hydrocortisone (HC) was used as a model drug, and the effect of the iminosulfuranes on the penetration of HC through hairless mouse skin was evaluated. All enhancers tested were applied to the skin as saturated suspensions in propylene glycol to ensure their maximum thermodynamic activity. Three compounds, S,S-dimethyl-N-(4-bromobenzoyl)iminosulfurane (9), S,S-dimethyl-N-(5-nitro-2-pyridyl)iminosulfurane (13), and S, S-dimethyl-N-(4-phenylazaphenyl)iminosulfurane (16) showed statistically significant activity quantitated by amounts of model drug permeated through the skin in 24 h (Q(24)), and flux values, compared to control (propylene glycol without enhancer). Highest Q(24) and flux values were obtained for 9: 996.2+/-192.5 microg/cm(2) and 42.9+/-7.5 microg/cm(2) per h, respectively. All arylsulfonyl substituted compounds showed lower or similar enhancement activity when compared to control. S, S-dimethyl-N-(benzenesulfonyl)iminosulfurane (1), S, S-dimethyl-N-(2-methoxycarbonylbenzenesulfonyl)iminosulfurane++ + ( 7) and S,S-dimethyl-N-(4-chlorobenzenesulfonyl)iminosulfurane (8) decreased the permeation of HC significantly (P<0.05). It is possible that these agents work as retardants under these experimental conditions. None of the enhancers tested showed significant skin model drug retention, suggesting that these compounds could be useful for increasing systemic rather than local drug delivery.