IN-VITRO EVALUATION OF A SERIES OF AZONE ANALOGS AS DERMAL PENETRATION ENHANCERS .4. AMINES

Dermal enhancement properties of 12 novel amine enhancers (Atone analo gs) were studied using in vitro diffusion cell techniques. Standard en hancers tested were Atone, didodecylamine, dodecylamine, and stearylam ine. The synthesis of these novel compounds is presented. Hydrocortiso ne 21-acetate was used as the model drug and its transdermal permeatio n and skin retention were examined using hairless mouse skin. Enhancem ent ratios (ER) were determined for flux, 24 h diffusion cell receptor concentrations (Q(24)), and 24 h full-thickness skin steroid content. ER for all parameters for control was 1.00. Control was no pretreatme nt of the skin. Al enhancers were applied at 0.4 M in propylene glycol 1 h prior to steroid application. N-dodecyldiethanolamine showed the greatest Q(24) value (ER 56.16) while N-(2-methoxyethyl)dodecylamine s howed the greatest skin retention (ER 2.0). Atone ER values were Q(24) 38.30 and skin retention 1.5, and those for didodecylamine were 13.06 and 1.1, respectively. In general, tertiary cyclic amine and secondar y amine enhancers showed less activity for flux than the tertiary acyc lic amine compounds.