The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants

G.R. Nanayakkara, A. Bartlett, B Forbes, C. Marriott, P.J. Whitfield, Marc Brown

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    43 Citations (Scopus)


    The model penetrants butyl paraben (BP), methyl paraben (MP) and caffeine (CF), because of their different octanol/water partition coefficients and postulated routes of permeation through human skin, were selected to assess the enhancing activity of pre-treatment solutions consisting of monounsaturated (oleic (OA) and palmitoleic (PA)) and poly-unsaturated (linoleic (LA)) fatty acids in benzyl alcohol (BA) using Franz diffusion cells and HPLC detection. Prior to assessing the effect of penetrant lipophilicity, NIP was chosen to investigate the concentration-dependent effect of fatty acids in pre-treatment solutions. At 5% (w/w) fatty acids in BA, only pre-treatment solutions containing palmitoleic acid (PA) increased the permeation of MP when compared to pre-treatment with BA alone, whereas at higher concentrations (10 and 20%, w/w), all pre-treatment solutions except 10% OA produced a significant increase in MP flux (P < 0.05). The general order of fatty acid effectiveness at any concentration was PA > LA > OA. At 20% (w/w) fatty acids in BA, all pre-treatment solutions significantly enhanced the permeation of all three penetrants (P<0.05) and an inverse relationship between penetrant lipophilicity and enhancement effect was observed. The permeation of BP was enhanced to a similar extent by all three fatty acids, whereas PA caused a significantly greater enhancement in the flux of both MP and CF when compared to CIA, LA and controls (P<0.05). It was proposed that the synergetic enhancement mechanisms of fatty acids and BA in pre-treatment solutions were augmenting the polar route by way of interactions with both polar and non-polar regions of stratum corneum lipids. Furthermore, the combination of PA and BA appears to be a good candidate as a penetration enhancer for hydrophilic molecules. (C) 2005 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)129-139
    Number of pages11
    JournalInternational Journal of Pharmaceutics
    Issue number1-2
    Publication statusPublished - 14 Sept 2005


    • palmitoleic acid
    • fatty acids
    • benzyl alcohol
    • transdermal
    • lipophilicity
    • IN-VITRO
    • RAT SKIN


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