Abstract
Dermal enhancement properties of 12 novel amine enhancers (Azone analogs) were studied using in vitro diffusion cell techniques. Standard enhancers tested were Azone, didodecylamine, dodecylamine, and stearylamine. The synthesis of these novel compounds is presented. Hydrocortisone 21-acetate was used as the model drug and its transdermal permeation and skin retention were examined using hairless mouse skin. Enhancement ratios (ER) were determined for flux, 24 h diffusion cell receptor concentrations (Q24), and 24 h full-thickness skin steroid content. ER for all parameters for control was 1.00. Control was no pretreatment of the skin. All enhancers were applied at 0.4 M in propylene glycol 1 h prior to steroid application. N-dodecyldiethanolamine showed the greatest Q24 value (ER 56.16) while N-(2-methoxyethyl)dodecylamine showed the greatest skin retention (ER 2.0). Azone ER values were Q24 38.30 and skin retention 1.5, and those for didodecylamine were 13.06 and 1.1, respectively. In general, tertiary cyclic amine and secondary amine enhancers showed less activity for flux than the tertiary acyclic amine compounds.
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