Bifonazole Loaded Cubosomal Gel for Topical Fungal Infections: Formulation and Optimization

The aim of this study was to develop Bifonazole-loaded cubosomal gel for the treatment of topical fungal infections, with the primary objective to increase the permeability and reduce the side effects of the drug.Bifonazole-loaded cubosomes were prepared using the top-down approach and optimized using the 3 3 Box-Behnken experimental design consisting of independent parameters Glyceryl monooleate, Poloxamer 407, and Cetyltrimethylammonium bromide, with dependent variables particle size, zeta potential, and entrapment efficiency.The particle size was found to increase with higher concentrations of Glyceryl monooleate while it decreased the zeta potential; increase in Poloxamer 407 and Cetyltrimethylammonium bromide concentration decreased the particle size.However, increased concentrations of Cetyltrimethylammonium bromide exhibited a positive charge.Entrapment efficiency improved with increasing concentrations of both Glyceryl monooleate and Cetyltrimethylammonium bromide.The optimized formulation showed a particle size of 170 nm, zeta potential of 26.64 mV, and entrapment efficiency of 80.45 %.TEM images displayed cubic particles with minimal curvature within the nano-size range.In-vitro studies indicated drug release upto 8 hours following Zero Order Kinetics and Higuchi model.The optimized Bifonazole loaded cubosomal gel, prepared with Xanthan gum (2% w/w) possessed suitable pH, viscosity, and spreadability compared to the gels prepared using Carbopol 934 and HPMC K4M.Comparative studies on the optimized Bifonazole loaded cubosomal gel, Bifonazole gel and marketed cream formulation demonstrated higher drug release, permeation rates with significant higher antifungal activity for optimised gel; safe use of formulation was demonstrated by histopathological studies.