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 (Q24), and 24 h full-thickness skin steroid content. Controls received no enhancer pretreatment of the skin. N-Dodecanoyl-L-proline (10) showed the highest Q24 value for total steroid (ER 13.7) while N-dodecanoyl-L-phenylalanine (5) showed the highest total steroid skin retention (ER 16.5).
Fincher
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TK
College of Pharmacy, University of South Carolina, Columbia 29208, USA.
Yoo
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SD
Player
M R
MR
Sowell
J W
JW
Michniak
B B
BB
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004058:Diffusion; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D006854:Hydrocortisone