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The influence of N, N-diethyl-m-toluamide (Deet) and 1-dodecylazacycloheptan-2-one (Azone), on skin permeability was examined for nifedipine (NP), taking into account their effects on the thermodynamic activity of the drug. The percutaneous absorption efficiency of NP was determined by measuring the drug concentration in rat plasma. Comparisons were made among NP suspensions in the enhancers to ensure equal thermodynamic activity. Azone increased NP penetration over that of propylene glycol (PG), while Deet produced a similar response to that of PG. The addition of a small amount of Deet to PG or diethyl sebacate (DES) provided for a rather large increase in NP penetration compared with that from PG or DES alone. The results of this study strongly suggest that Deet and Azone have different modes of action. Azone exerted a genuine effect on the skin and produced marked improvement in the penetration of NP. The effect of Deet was interesting as it was effective only in combination with other vehicles. Deet exhibits excellent solubilizing properties and penetrates the skin easily. Accordingly, it may be concluded that Deet functions simply as a cosolvent to produce saturated or supersaturated solutions of the active ingredient by its rapid disappearance from the vehicle, and thereby maximizes the thermodynamic activity of the drug.

Effects of penetration enhancers on percutaneous absorption of nifedipine. Comparison between Deet and Azone.