INVITRO EVALUATION OF A SERIES OF AZONE ANALOGS AS DERMAL PENETRATION ENHANCERS .1.

The influence of a series of Azone analogs on the percutaneous penetration of a lipophilic model drug (hydrocortisone-21-acetate) across hairless mouse skin has been investigated. Methods of synthesis of these novel compounds are also described. Permeability studies utilized vertical non-occluded Franz cells at 37-degrees-C and propylene glycol as the vehicle for the drug. Enhancers were applied one h prior to drug treatment in the same vehicle. Three enhancers were applied at their maximum saturation solubilities in propylene glycol, the rest of the compounds at 0.4 M. Enhancement ratios were calculated for flux, 24 h diffusion cell receptor concentrations, and full-thickness skin total steroid contents. All enhancers were found to increase permeation parameters to a greater or lesser extent over control. A few compounds were found to be more effective than Azone in increasing these parameters; particularly skin retention of the model drug.