Department of Pharmacy and Pharmaceutical Technology and Physicochemistry, Faculty of Pharmacy and Food Sciences, Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain.
Almirall SA, Carrer de Laureà Miró, 390, 08980 Sant Feliu de Llobregat, Barcelona, Spain.
Int J Pharm. 2019 Oct 5;569:118531. doi: 10.1016/j.ijpharm.2019.118531. Epub 2019 Jul 16.
Novel emulsions with a nanostructured continuous phase have been proposed as controlled drug delivery systems to enhance topical delivery of active ingredients avoiding systemic effects. In this study, oil-in-water (O/W) emulsions with two surfactant/water (S/W) weight ratios of 40:60 and 35:65, and oil concentrations of 10 wt% (diluted emulsion), 40 wt% (concentrated emulsion) and 85 wt% (highly concentrated emulsion) have been investigated to identify the presence of liquid crystalline structures and their influence on drug release and skin permeation. The emulsions have been characterized in terms of visual appearance, rheology and drug release. The presence of cubic liquid crystalline structures in emulsions with S/W 40:60 was confirmed by small angle X-ray scattering (SAXS). Rheology results showed a markedly different behaviour in emulsions with S/W 40:60 compared with nonstructured emulsions. A model drug, diclofenac sodium (DS) was successfully incorporated in the emulsions. DS release was studied with hydrophilic and lipophilic membranes, and the amount of DS in the receptor solution was significantly lower in the formulations containing cubic liquid structures. An in vitro skin permeation study with dermatomed human skin showed that emulsions with a nanostructured continuous phase are suitable formulations for topical delivery with DS retention in skin layers. The results indicate that the amount of drug retained in skin structures may be tuned by modification of liquid crystal concentration and emulsion structure.
已经提出了具有纳米结构连续相的新型乳剂作为控制药物传递系统，以增强活性成分的局部递送，避免全身效应。在这项研究中，研究了两种表面活性剂/水（S/W）重量比为 40:60 和 35:65 的油包水（O/W）乳液，以及油浓度为 10wt%（稀释乳液）、40wt%（浓缩乳液）和 85wt%（高浓度乳液）的乳液，以确定是否存在液晶结构及其对药物释放和皮肤渗透的影响。通过小角度 X 射线散射（SAXS）确认了 S/W 为 40:60 的乳液中立方液晶结构的存在。流变学结果表明，S/W 为 40:60 的乳液与非结构化乳液的行为明显不同。将模型药物双氯芬酸钠（DS）成功掺入乳液中。用亲水和疏油膜研究了 DS 的释放，并且在含有立方液晶结构的制剂中，受体溶液中的 DS 量明显更低。用人脱细胞皮肤进行的体外皮肤渗透研究表明，具有纳米结构连续相的乳液是适用于局部递送 DS 的制剂，DS 在皮肤层中的保留。结果表明，通过改变液晶浓度和乳液结构，可以调节药物在皮肤结构中的保留量。
