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

Abstract

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 topical formulation of a special drug. In this study, the structural requirements of penetration enhancers have been investigated using the Quantitative Structure-Activity Relationship (QSAR) technique. Activities of naturally occurring terpenes, pyrrolidinone and Nacetylprolinate derivatives on the skin penetration of 5-fluorouracil, diclofenac sodium, hydrocortisone, 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.3

The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation

“…Kang et al (2007) determined permeability coefficient of different terpenes experimentally using human skin and employed non-linear regression model. Their results suggested that (a) liquid terpenes have a tendency to produce ameliorate enhancing effects than solid terpenes; (b) terpenes with higher Log P values were more effective enhancers than those with smaller Log P as it was easier for lipophilic terpenes to get mixed with stratum corneum intercellular lipids (Ghafourian et al 2004;Narishetty and Panchagnula 2004a).…”

Percutaneous Permeation Enhancement by Terpenes: Mechanistic View

“…These QSAR models provide an insight into the mechanism of skin penetration and guidance for predicting permeability of new compounds. Ghafourian et al constructed QSAR models for 34 terpenes, 16 pyrrolidinone derivatives and seven N-acetylprolinate esters with respect to several drugs (83). These QSAR models were based on data of different sources and skin types, including human, rats and hairless mouse skins.…”

Review on Transdermal Drug Delivery Systems

“…Some researcher have reported that the (-) enantiomer of a terpene is more effective than the corresponding (±) racemate or the (+) isomer. Futhermore, some terpenes with a minimal degree of saturation are more effective enhancers to deliver the hydrophilic drugs [32,33].…”

“…Some researcher have reported that the (-) enantiomer of a terpene is more effective than the corresponding (±) racemate or the (+) isomer. Futhermore, some terpenes with a minimal degree of saturation are more effective enhancers to deliver the hydrophilic drugs [32,33].Annex Publishers | www.annexpublishers.com 2. The lipophilicity of terpenes: High lipophilicity is an important structural feature for terpenes; accordingly, hydrocarbon, nonpolar terpenes, such as limonene, are more effective to promote the transdermic absorption of lipophilic drugs than oxygencontaining polar terpenes and vice versa [34,35].…”