A New Topical Fluconazole Microsponge Loaded Hydrogel: Preparation and Characterization

Invasive fungal infections can be devastating, especially in immunocompromized patients. Oral administration of fluconazole (FLZ) often produces gastric irritation, heart-burn, vomiting and sometimes patient can develop ulceration resulting in a less patient compliance with long term therapy. The aim of the present study was to formulate topical microsponge-based delivery system containing FLZ for controlled release of the drug and consequently avoiding its oral side effects. Ethyl cellulose (EC) and Eudragit RS 100 based microsponges were prepared using quasi-emulsion solvent diffusion method. The effect of formulation variables such as drug to polymer ratio, polymer type, polyvinyl alcohol (PVA) concentration and type of internal phase on the physical characteristics of the microsponges was examined using 24 factorial design. Results revealed that FLZ loading and microsponge particle size were increased with increasing the polymer fraction. Moreover, EC significantly increased the drug entrapment efficiency (EE%) and the mean particle size. There was a reverse proportionality between the PVA concentration and both the EE% and the mean particle size. Regarding the solvent type, ethanol significantly increased the EE% and the particle size when compared to methylene chloride. A selected FLZ microsponge (F3, containing FLZ and EC in 1:1 ratio and prepared using 0.75% PVA and methylene chloride) was incorporated in carbopol gel formulation and evaluated for its in vitro release characteristics. The developed microsponges were spherical and porous. There was no interaction between drug and polymer molecules. The drug release through cellulose dialysis membrane showed fickian release pattern. Further antifungal activity and in vivo animal studies for the obtained formula are recommended.