Enhancing effect of pyrrolidone derivatives on transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen.

The enhancing effects of pyrrolidone derivatives on the transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen were studied by using an in vitro technique and full-thickness rat skin. The enhancers included 1-methyl (1), 1-hexyl (2), and 1-lauryl-2-pyrrolidone (3). Penetrants with various physicochemical properties were used. Flurbiprofen penetrated through skin rapidly after application alone. 5-Fluorouracil, triamcinolone acetonide, and indomethacin showed little penetration. Pyrrolidone derivatives enhanced the penetration of penetrants, especially the lipophilic compounds 2 and 3, which showed a great enhancing effect on the penetration of 5-fluorouracil and indomethacin. Pyrrolidone derivatives also enhanced the solubility of these penetrants in isopropyl myristate. Compounds 2 and 3 showed greater enhancing effects on the solubility and penetration of hydrophilic penetrants than those of lipophilic penetrants. These results suggest that the pyrrolidone derivatives enhance the flux of penetrants in skin by increasing the solubility of penetrants in the stratum corneum. Compounds 1 and 2 were detected in the receptor phase. All enhancers accumulated to a great extent in the skin. These derivatives also enhanced the skin retention of drug. It is concluded that these pyrrolidone derivatives are useful for transdermal drug delivery, although further studies are necessary before they could be used clinically.