Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 255, Issue 1-2, Pages 153-166Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0378-5173(03)00086-3
Keywords
percutaneous absorptio; flurbiprofen; enhancer; irritation; bioengineering method; cell culture
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The efficacy and safety of commonly used enhancers were systemically evaluated by in vitro and in vivo methods in this study. Flurbiprofen was used as the model drug to examine the enhancing capacity of these enhancers. Both in vitro permeation by Franz cells and in vivo kinetics of skin disposition were performed to determine the flurbiprofen permeation by enhancers. Unsaturated fatty acids showed the greatest enhancement of flurbiprofen permeation. The enhancing effect of D-limonene was slightly lower than that of fatty acids. Azone and L-alpha-lecithin even reduced the skin deposition by flurbiprofen application. In vitro prostaglandin E-2 (PGE(2)) release by cell culture, in vivo transepidermal water loss (TEWL) and colorimetry, and skin morphological changes were determined to examine the irritation of the skin by enhancers. The results showed that skin disruption and inflammation did not necessary correspond to the enhancing efficiency of the enhancers. Moreover, some discrepancies were observed in these irritant profiles when using various methods. The fatty acids generally showed the most irritating properties, followed by Azone, D-limonene, and L-alpha-lecithin. A complete portrait of the efficacy and safety of commonly used enhancers was therefore established in this study. (C) 2003 Elsevier Science B.V. All rights reserved.
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