Ossowicz Paula, Klebeko Joanna, Janus Ewa, Nowak Anna, Duchnik Wiktoria, Kucharski Łukasz, Klimowicz Adam
West Pomeranian University of Technology, Szczecin, Faculty of Chemical Technology and Engineering, Department of Chemical Organic Technology and Polymeric Materials Piastów Ave. 42 71-065 Szczecin Poland
Pomeranian Medical University in Szczecin, Department of Cosmetic and Pharmaceutical Chemistry Powstańców Wielkopolskich Ave. 72 70-111 Szczecin Poland.
RSC Adv. 2020 Nov 16;10(68):41727-41740. doi: 10.1039/d0ra06567f. eCollection 2020 Nov 11.
The effect of various alcohols as vehicles on skin permeability was compared for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with l-valine alkyl esters [ValOR][IBU], in which the alkyl chain R was changed from C1 to C8. permeation experiments were conducted in a Franz cell with porcine skin. Methanol, ethanol, and isopropanol solutions of 70% (v/v) were chosen as vehicles for penetrants and a buffer solution of pH 5.4 or 7.4 as the acceptor phase. The comparisons of permeation profiles for various [ValOR][IBU] from different alcohols were determined. The cumulative mass, skin accumulation, steady-state flux, diffusion coefficient, and lag time were investigated and compared. It was observed that -propanol was the best enhancer of skin permeation of both unmodified ibuprofen and its salts with l-valine alkyl esters for both acceptor phases. The permeability of the various carriers increases with increasing chain-length of the alcohol. In most cases, significantly higher cumulative mass was found in the acceptor buffer of pH 7.4. The conjugate of ibuprofen with l-valine propyl ester [ValOPr][IBU] permeated the skin to the highest degree in comparison to unmodified ibuprofen. The accumulation of ibuprofen was higher for all salts in relation to the parent acid applied onto the skin. The greatest amounts of ibuprofen were accumulated in the skin when ibuprofen was used as the ionic pair with l-valine butyl ester, [ValOBu][IBU] in the -propanol solution and pH 7.4 buffer as the acceptor phase.
比较了各种醇类作为载体对未修饰的布洛芬（IBU）以及布洛芬与L-缬氨酸烷基酯[ValOR][IBU]的离子对（其中烷基链R从C1变化到C8）皮肤渗透性的影响。在Franz扩散池中和猪皮上进行渗透实验。选择70%（v/v）的甲醇、乙醇和异丙醇溶液作为渗透剂的载体，并选择pH 5.4或7.4的缓冲溶液作为接受相。确定了不同醇类中各种[ValOR][IBU]渗透曲线的比较。研究并比较了累积质量、皮肤蓄积量、稳态通量、扩散系数和滞后时间。观察到，对于两个接受相而言，正丙醇是未修饰的布洛芬及其与L-缬氨酸烷基酯盐类皮肤渗透的最佳增强剂。各种载体的渗透性随着醇类链长的增加而增加。在大多数情况下，在pH 7.4的接受缓冲液中发现了显著更高的累积质量。与未修饰的布洛芬相比，布洛芬与L-缬氨酸丙酯的共轭物[ValOPr][IBU]对皮肤的渗透程度最高。与涂抹在皮肤上的母体酸相比，所有盐类中布洛芬的蓄积量更高。当布洛芬与L-缬氨酸丁酯形成离子对[ValOBu][IBU]，以正丙醇溶液为载体且pH 7.4的缓冲液为接受相时，皮肤中蓄积的布洛芬量最大。
