Preparation of alkyl-substituted pyrrolidone derivatives and their evaluation as transdermal penetration enhancers.
The preparation of novel transdermal penetration enhancers derived from 2-pyrrolidone were carried out, and the enhancing activities of drug permeation through the skin were evaluated by means of in vitro experiment. All the enhancers contain a short alkyl group, such as methyl, ethyl, propyl or butyl group, at 1-position and a dodecyl group at 3-position of 2-pyrrolidone ring. The enhancing activities were considerably influenced by the length of the short alkyl group at 1-position. 1-Propyl and 1-butyl-3-dodecyl-2-pyrrolidone showed the effective enhancement of penetration of indomethacin through the skin in 60 wt% ethanolic aqueous solution. Moreover, the similar enhancing activities of these compounds were also observed even in ethanolic vehicle.
Aoyagi
T
T
Sagami Chemical Research Center, Kanagawa, Japan.
Yamamura
M
M
Suzuki
N
N
Matsui
K
K
Nagase
Y
Y
D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007213:Indomethacin / Q000493:pharmacokinetics; D008297:Male; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D012869:Skin Absorption / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001381:Azepines; D011760:Pyrrolidinones; C035229:laurocapram; D007213:Indomethacin