Cubic liquid crystalline structures in diluted, concentrated and highly concentrated emulsions for topical application: Influence on drug release and human skin permeation

摘要

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.