In vitro evaluation of a series of N-dodecanoyl-L-amino acid methyl esters as dermal penetration enhancers

A series of N-dodecanoyl-L-amino acid methyl esters (1-10) and n-pentyl N-acetylprolinate (11) were evaluated for dermal enhancement properties using an in vitro diffusion cell technique. Methods of synthesis of these compounds were described. Enhancers were applied 1 h prior to drug treatment. Hydrocortisone was used as the model drug and was applied to excised hairless mouse skin as a saturated suspension in propylene glycol. Enhancement ratios (ER) were determined for permeability coefficient, 24 h diffusion cell receptor concentration (Q(24)), and 24 h full-thickness skin steroid content. Controls received no enhancer pretreatment of the skin. N-Dodecanoyl-L-proline (10) showed the highest Q(24) value for total steroid (ER 13.7) while N-dodecanoyl-L-phenylalanine (5) showed the highest total steroid skin retention (ER 16.5).