IN-VITRO EVALUATION OF A SERIES OF AZONE ANALOGS AS DERMAL PENETRATION ENHANCERS .3. ACYCLIC AMIDES

A series of acyclic amides was synthesized and tested for enhancement properties using excised hairless mouse skin and hydrocortisone 21-acetate as the model drug. All compounds were applied at 0.4 M (or at their respective saturation solubilities) in propylene glycol. Atone (0.4 M) was used as a standard enhancer. Enhancement ratios were calculated for flux, 24 h diffusion cell receptor concentrations (Q(24)) and 24 h full-thickness mouse skin steroid content. Enhancer 5 showed the highest activity for flux (35.22-fold over control), 24 h receptor concentration (79.86-fold over control) and skin drug content (4.3-fold over control). These enhancement ratios were higher than those for Atone which were 19.51, 38.30 and 1.5-fold over control, respectively. Enhancers 4, 10 and 11 showed similar Q(24) values to Atone, and 3, 9 and 10 increased skin steroid content to a greater extent than Atone.