Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation study

The basic properties and the in vitro release rate kinetics of azelaic acid (AA), alternatively vehiculated in different phospholipid-based vesicles such as ethosomes or liposomes, were investigated. Ethosomes were produced by a simple method based on addition of an aqueous phase to an ethanol solution (comprised between 20\% and 45%, v/v) of soy phosphatidyl choline (5%, w/w) and AA (0.2%, w/w) under mechanical stirring. Liposomes were obtained by the same composition in the absence of ethanol with the reverse-phase evaporation method. Vesicle size was measured by photon correlation spectroscopy (PCS), evidencing smaller mean diameters and narrower dimensional distributions in the case of ethosomes with respect to liposomes. In order to obtain homogeneously sized vesicles, both ethosomal and liposomal dispersions were extruded through polycarbonate membranes with pores of calibrated diameter (400 nm and 200 nm). Vesicle morphology was characterized by freeze-fracture scanning electron microscopy (SEM) showing the presence of unilamellar vesicles both in liposome- and in ethosome-based dispersions. Free energy measurements of the vesicle bilayers were conducted by differential scanning calorimetry (DSC). AA diffusion from ethosomal or liposomal dispersions and from ethosomes and liposomes incorporated in a viscous gel was investigated by a Franz cell assembled with synthetic membranes. The release rate was more rapid from ethosomal systems than from liposomal systems. In particular, ethosomes produced by the highest ethanol concentration released AA more rapidly, and the same trend was found using viscous forms.