Hoppel Magdalena, Mahrhauser Denise, Stallinger Christina, Wagner Florian, Wirth Michael, Valenta Claudia
Research Platform 'Characterisation of Drug Delivery Systems on Skin and Investigations of Involved Mechanisms', University of Vienna, Vienna, Austria.
J Pharm Pharmacol. 2014 May;66(5):658-67. doi: 10.1111/jphp.12194. Epub 2013 Dec 23.
The aim of this study was to create multiple water-in-oil-in-water (W/O/W) emulsions with an increased long-term stability as skin delivery systems for the hydrophilic model drug 5-fluorouracil.
Multiple W/O/W emulsions were prepared in a one-step emulsification process, and were characterized regarding particle size, microstructure and viscosity. In-vitro studies on porcine skin with Franz-type diffusion cells, tape stripping experiments and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) were performed.
The addition of Solagum AX, a natural polymer mixture of acacia and xanthan gum, led to multiple W/O/W emulsions with a remarkably increased long-term stability in comparison to formulations without a thickener. The higher skin diffusion of 5-fluorouracil from the multiple emulsions compared with an O/W-macroemulsion could be explained by ATR-FTIR. Shifts to higher wave numbers and increase of peak areas of the asymmetric and symmetric CH2 stretching vibrations confirmed a transition of parts of the skin lipids from an ordered to a disordered state after impregnation of porcine skin with the multiple emulsions.
Solagum AX is highly suitable for stabilization of the created multiple emulsions. Moreover, these formulations showed superiority over a simple O/W-macroemulsion regarding skin permeation and penetration of 5-fluorouracil.
本研究的目的是制备具有更高长期稳定性的多重水包油包水（W/O/W）乳液，作为亲水性模型药物5-氟尿嘧啶的皮肤给药系统。
采用一步乳化法制备多重W/O/W乳液，并对其粒径、微观结构和粘度进行表征。使用Franz型扩散池对猪皮进行体外研究、胶带剥离实验以及衰减全反射傅里叶变换红外光谱（ATR-FTIR）分析。
添加Solagum AX（一种阿拉伯胶和黄原胶的天然聚合物混合物）后得到的多重W/O/W乳液，与未添加增稠剂的配方相比，长期稳定性显著提高。通过ATR-FTIR分析可知，与O/W型宏观乳液相比，多重乳液中5-氟尿嘧啶在皮肤中的扩散性更高。在猪皮用多重乳液浸渍后，不对称和对称CH2伸缩振动的波数向更高值移动以及峰面积增加，证实了部分皮肤脂质从有序状态转变为无序状态。
Solagum AX非常适合用于稳定所制备的多重乳液。此外，这些配方在5-氟尿嘧啶的皮肤渗透方面表现出优于简单O/W型宏观乳液的性能。
