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-penty l N-acetylprolinate (11) were evaluated for dermal enhancement propert ies using an in vitro diffusion cell technique. Methods of synthesis o f these compounds were described. Enhancers were applied 1 h prior to drug treatment. Hydrocortisone was used as the model drug and was appl ied to excised hairless mouse skin as a saturated suspension in propyl ene glycol. Enhancement ratios (ER) were determined for permeability c oefficient, 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 highe st Q(24) value for total steroid (ER 13.7) while N-dodecanoyl-L-phenyl alanine (5) showed the highest total steroid skin retention (ER 16.5).