Nanayakkara Gihan R, Bartlett Ann, Forbes Ben, Marriott Chris, Whitfield Phil J, Brown Marc B
Department of Pharmacy, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Int J Pharm. 2005 Sep 14;301(1-2):129-39. doi: 10.1016/j.ijpharm.2005.05.024.
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.
由于对羟基苯甲酸丁酯（BP）、对羟基苯甲酸甲酯（MP）和咖啡因（CF）这几种渗透剂具有不同的辛醇/水分配系数以及假定的透过人体皮肤的渗透途径，因此选择它们来评估由单不饱和脂肪酸（油酸（OA）和棕榈油酸（PA））和多不饱和脂肪酸（亚油酸（LA））在苯甲醇（BA）中组成的预处理溶液的增强活性，采用Franz扩散池和高效液相色谱检测法。在评估渗透剂亲脂性的影响之前，选择MP来研究预处理溶液中脂肪酸的浓度依赖性效应。在BA中含有5%（w/w）脂肪酸时，与单独用BA预处理相比，只有含有棕榈油酸（PA）的预处理溶液增加了MP的渗透，而在较高浓度（10%和20%，w/w）时，除10% OA外的所有预处理溶液均使MP通量显著增加（P<0.05）。在任何浓度下，脂肪酸有效性的一般顺序为PA>LA>OA。在BA中含有20%（w/w）脂肪酸时，所有预处理溶液均显著增强了所有三种渗透剂的渗透（P<0.05），并且观察到渗透剂亲脂性与增强效果之间呈反比关系。所有三种脂肪酸对BP渗透的增强程度相似，而与OA、LA和对照相比，PA对MP和CF通量的增强作用显著更大（P<0.05）。有人提出，预处理溶液中脂肪酸和BA的协同增强机制是通过与角质层脂质的极性和非极性区域相互作用来增强极性途径。此外，PA和BA的组合似乎是亲水性分子良好的渗透促进剂候选物。
