Dept. Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, University of Cagliari, Cagliari 09124, Italy.
Dept. Scienze Chimiche e Geologiche, University of Cagliari, SS 554 Bivio Sestu, 09042, Monserrato (CA), Italy.
Colloids Surf B Biointerfaces. 2018 Feb 1;162:8-15. doi: 10.1016/j.colsurfb.2017.11.012. Epub 2017 Nov 6.
The poor ability of many drugs to cross skin layers is the main limiting factor for the exploitation of the transdermal route for drug delivery. As a consequence, several approaches have been proposed to overcome the skin barrier, such as the inclusion of penetration enhancers in the topically applied drug solutions and emulsions. In this work, the penetration enhancer diethylene glycol monoethyl ether was included in novel diclofenac acid nanocrystal formulations, developed using the wet media milling technique and Poloxamer 188 as stabilizer. The nanosuspensions were characterized by different techniques such as scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and photon correlation spectroscopy. The influence of diethylene glycol monoethyl ether on (trans)dermal delivery of diclofenac nanosuspensions was evaluated by in vitro studies using Franz diffusion cells and pig skin.
demonstrated that the presence of diethylene glycol monoethyl ether influences the Poloxamer 188 ability to stabilize the nanocrystals during the milling process, leading to larger particles as compared to penetration enhancer-free nanosuspensions. As previously reported, the in vitro permeation studies indicate the nanosizing as a key factor in the dermal penetration of topically applied diclofenac. Surprisingly enough, the inclusion of increasing amounts of the penetration enhancer in the formulation decreased the diclofenac accumulation in the stratum corneum, while showing no significant effect on the drug delivered to the epidermis. Overall, the present results exclude a synergistic effect of the nanosizing approach and the addition of diethylene glycol monoethyl ether in regard to the skin penetration of diclofenac applied as a nanosuspension.
许多药物穿透皮肤层的能力较差，这是限制经皮给药途径开发的主要因素。因此，已经提出了几种方法来克服皮肤屏障，例如在局部应用的药物溶液和乳剂中加入渗透增强剂。在这项工作中，将二乙二醇单乙醚作为渗透增强剂加入到使用湿介质研磨技术和泊洛沙姆 188 作为稳定剂开发的新型双氯芬酸酸纳米晶体制剂中。通过扫描电子显微镜、差示扫描量热法、X 射线粉末衍射、傅里叶变换红外光谱和光子相关光谱等不同技术对纳米混悬剂进行了表征。通过使用 Franz 扩散池和猪皮进行体外研究评估了二乙二醇单乙醚对双氯芬酸纳米混悬剂（经）皮传递的影响。
结果表明，二乙二醇单乙醚的存在会影响泊洛沙姆 188 在研磨过程中稳定纳米晶体的能力，导致与不含渗透增强剂的纳米混悬剂相比，颗粒更大。如前所述，体外渗透研究表明，纳米化是局部应用双氯芬酸经皮渗透的关键因素。令人惊讶的是，制剂中渗透增强剂含量的增加会降低角质层中双氯芬酸的积累，而对表皮中药物的传递没有显著影响。总的来说，目前的结果排除了纳米化方法和添加二乙二醇单乙醚协同作用对双氯芬酸经皮渗透的影响，双氯芬酸以纳米混悬剂形式应用。
