Percutaneous delivery of econazole using microemulsion as vehicle: formulation, evaluation and vesicle-skin interaction

Abstract

This project was carried out to exploit the feasibility of using microemulsion (ME) as an alternative carrier for percutaneous delivery econazole nitrate (ECN) and elucidate the underlying mechanism of permeation enhancement. The ME was developed based on Labrafil M 1944 Cs as oil phase, Solutol HS15 and Span 80 as surfactants, Transcutol P as cosurfactant and water as aqueous phase. The solubility of ECN was firstly determined for screening the ingredients of the system. Pseudo-ternary phase diagrams were constructed to formulate ME and select surfactant and cosurfactant. Central composite design-response surface methodology (CCD-RSM) was utilized to optimize the formulation of ME. The ECN loaded ME was characterized in terms of morphology, particle size and size distribution, pH value, refractive index, viscosity and conductivity, and storage stability of the ECN loaded ME was assayed. Percutaneous permeation of ECN from ME in vitro through rat skin was investigated in comparison with PBS aqueous suspension (1%, w/w), and results showed that ME enhanced drug retention in the skin and permeation through the skin, the enhancement of ME on skin deposition was further visualized through fluorescent-labeled ME by confocal laser scanning microscope (CLSM). The action mechanism of ME on improving percutaneous delivery was studied by performing a pretreatment test. It can speculate that ME does not simply behave as enhancer but it also acts as drug carrier. Furthermore, ME-skin interaction was elucidated through transmission electron microscope (TEM), and attenuated total reflectance fourier-transform infrared (ATR-FTIR). TEM was performed to visualize the micro morphological change of skin. ATR-FTIR was carried out to investigate the molecular vibrations of the components of stratum corneum (SC). The results indicate that the ME system may be a promising vehicle for percutaneous delivery of ECN.

Keywords: ATR-FTIR; CLSM; Econazole nitrate; Econazole nitrate (PubChem CID: 68589); Microemulsion; Percutaneous delivery; TEM; Vesicle-skin interaction.