Miconazole Nitrate based cubosome hydrogels for topical application

Abstract

Cubosomes are discrete, sub-micron, nano-structured particles of bicontinuous cubic liquid crystalline phase. Cubosomes consist of honeycombed (cavernous) structures separating two internal aqueous channels and a large interfacial area. They are the biocompatible novel approach for the drug delivery system. The controlled release application of these nanoparticles is of a great significance in cosmeceutical and pharmaceutical fields. The present study is concerned with the design and evaluation of a novel nano-particulate system; cubosomes, loaded with miconazole nitrate (MN); which is used as antifungal agent. Cubosome dispersions were formulated by emulsification technique using different concentrations of a lipid phase monoolein and the nonionic surfactant, Poloxamer 407. The prepared cubosomal dispersions were characterized regarding dimensional distribution, particle size, and in vitro drug release. The optimum formulae were incorporated in a CMC or HPMC based hydrogels, to form cubosomal hydrogels (cubogels). The cubogels were characterized regarding in vitro release of (MN), viscosity and pH. A comparison between the cubogels and a commercially available product, Miconaz ® cream, was carried out to judge their efficacy. The drug release from the commercial preparation was lower than all the prepared nano-emulsion based gel formulations. G1 and G8 showed highest drug release percent (100%) after 8 hours, in contrast the marketed formulation released (44.8%) of the drug after 8 hrs. The in vitro Miconazole nitrate release data were fitted to Korsmeyerpeppa's release model. The formulation exhibited non-fickian transport with zero order kinetics. Formulae G1, G8 and G10, that showed both small droplet size and highest extent of drug release, were microbiologically evaluated against Candida albicans ( C. albicans ) using agar cup diffusion method. The selected formulae showed superior antimycotic activity compared to the commercially available formulation.