The effect of penetration enhancers on drug delivery through skin: A QSAR study

Ghafourian, Taravat, Zandasrar, Parinaz, Hamishekar, Hamed and Nokhodchi, Ali (2004) The effect of penetration enhancers on drug delivery through skin: A QSAR study. Journal of Controlled Release, 99 (1). pp. 113-125. ISSN 0168-3659

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Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. A full understanding of the mode of action could be beneficial for the design of potent enhancers and for the choice of the enhancer to be used in the topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structurea-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and N-acetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium (DFS), hydrocortisone (HC), estradiol and benazepril have been considered. The resulting QSARs indicated that for 5-fluorouracil and diclofenac sodium, less hydrophobic enhancers were the most active. More precisely, molecular descriptors in the corresponding QSARs indicated the possible involvement of intermolecular electron donor-acceptor interactions. This was in contrast to the skin permeation promotion of hydrocortisone, estradiol and benazepril by enhancers, where a linear relationship between enhancement activity and n-octanol/water partition coefficients of enhancers was evident. The possible mechanisms of penetration enhancement as suggested by the QSARs will be discussed. © 2004 Elsevier B.V. All rights reserved.

Item Type: Article
Keywords: Intermolecular interactions; Penetration rate; Skin permeation, Derivatives; Drug dosage; Drug interactions; Hydrophobicity; Molecular dynamics, Skin, 2 pyrrolidone derivative; 3 carene; ascaridole; benazepril; bisabolol; carveol; cineole; cymene; diclofenac; drug vehicle; estradiol; farnesol; fluorouracil; geraniol; hydrocortisone; menthol; menthone; n acetylprolinate derivative; nerolidol; octanol; phytol; piperitone; proline derivative; pulegone; pyrrolidine derivative; terpinen 4 ol; terpineol; thymol; unclassified drug; unindexed drug; verbenone, article; controlled study; drug delivery system; drug formulary; drug penetration; drug structure; electron; human; human tissue; partition coefficient; priority journal; quantitative structure activity relation; skin penetration; skin permeability, Administration, Cutaneous; Animals; Benzazepines; Diclofenac; Estradiol; Fluorouracil; Humans; Hydrocortisone; Mice; Mice, Inbred HRS; Molecular Structure; Proline; Pyrrolidinones; Skin Absorption; Structure-Activity Relationship; Terpenes
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 30 Nov 2017 10:02
Last Modified: 02 Jul 2019 17:18

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