The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants.
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, MP 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 OA, 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.
Nanayakkara
Gihan R
GR
Department of Pharmacy, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Bartlett
Ann
A
Forbes
Ben
B
Marriott
Chris
C
Whitfield
Phil J
PJ
Brown
Marc B
MB
D000465:Algorithms; D019905:Benzyl Alcohol / Q000494:pharmacology*; D002110:Caffeine / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D015194:Diffusion Chambers, Culture; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D010226:Parabens / Q000493:pharmacokinetics*; D010539:Permeability; D010592:Pharmaceutic Aids; D012869:Skin Absorption / Q000187:drug effects*; D012996:Solutions
D000697:Central Nervous System Stimulants; D005231:Fatty Acids, Unsaturated; D010226:Parabens; D010592:Pharmaceutic Aids; D012996:Solutions; D002110:Caffeine; C038091:butylparaben; C015358:methylparaben; D019905:Benzyl Alcohol