n-pentyl N-acetylprolinate. A new skin penetration enhancer

The activity of n-pentyl N-acetylprolinate (PNAP) as a transdermal penetration enhancer was investigated. PNAP was synthesized from L-proline by acetylation with acetic anhydride, followed by acid-catalyzed esterification with 1-pentanol. Structure confirmation was accomplished by IR and NMR spectroscopy and elemental analysis. Benzoic acid (BA) was used as a model drug, and the effect of PNAP on the flux of BA through human cadaver skin was evaluated. The central nervous system (CNS) toxicity of PNAP was evaluated by comparing the effects of intraperitoneal administration of PNAP to mice with those of laurocapram (Azone), a known penetration enhancer. Based on preliminary studies, PNAP appears to be an effective transdermal penetration enhancer, is nontoxic at low doses, and exhibits dose-related CNS toxicity at higher doses.