Formulation Development and Evaluation of Niosomal Gel of Combined Anti-Fungal Agents

Irene Thomas*, Beena P, Elessy Abraham

Miconazole, glucocorticoid antagonist and Terbinafine, Sqalene epoxidase inhibitor are two of the commonly used drug for fungal diseases. In this present work, Miconazole and Terbinafine in combination was formulated as Niosomal gel and evaluated. Niosomes containing both the drugs were prepared by thin film evaporation technique with varying concentration of Nonionic surface active agent, Span 60 and cholesterol. FTIR and DSC study reports confirmed the absence of incompatibilities between the two drugs and the excipients. Five Niosomal formulations were prepared (N1- N5) and evaluated for surface morphology, particle size, PDI, Drug content, entrapment efficiency, Zeta potential, in vitro drug release and TEM analysis. The formulation (N3) containing equal concentration of Span 60 (100 mg) and Cholesterol (100 mg) showed highest yield, drug content and its entrapment efficiency was found to be 91.06%. All the Niosomal dispersions were incorporated into 2% Carbopol gel base to produce five Niosomal gel formulations NG1–NG5. Niosomal gels were evaluated for physical properties, pH, Viscosity, Spreadability, Extrudability, Drug content and in vitro drug release. NG3 was found to be the best formulation as it showed promising qualities of a gel with a maximum release of 84.523% (MCZ) and 85.812% (TBF) after 8 hrs and maximum anti-fungal activity than all the other Niosomal gel formulations. From the antifungal activity carried out, Zone of inhibition of two drugs in combination was found to be greater than the zone inhibition of individual pure drugs indicating the synergistic activity of the drugs. Skin irritation studies were conducted in Egg CAM and all the formulations showed non-irritant reports. Niosomal gel showed good stability at various temperatures. The kinetic data analysis showed that Niosomal gel fits to Higuchi model and follows zero order release by non-fickian super case ??? diffusion. All these findings proved that Niosomal gel containing combined antifungal drugs is more effective than the marketed plain gel containing a single antifungal agent. Since the two drugs are having different mechanism of action they overcome the anti-fungal resistance shown by the organism and broaden the fungal spectrum. Moreover Niosomal gel improves the topical formulation with a high degree of skin permeation and prolongs maintenance of drug by increasing the retention time in the target area at a therapeutic level thereby decreasing the frequency of administration and increasing patient compliance.