Design, fabrication and evaluation of clotrimazole loaded polymeric microsphere based in situ ophthalmic gel

The present study was started with aim to design clotrimazole loaded polymeric microsphere based in situ  ophthalmic gel for management of corneal fungal infections. The clotrimazole loaded microsphere was fabricated using various percentage of polylactide-co-glycolide polymer by solvent evaporation technique and evaluated for particle size, zeta potential and encapsulation efficiency. The polyvinyl alcohol was used as stabilizer. The formulation batch which showed good particle size and entrapment efficiency was selected for further study. The in situ  ophthalmic gel of optimized drug loaded microsphere was formulated using various ratios of sodium alginate and hydroxy propyl methyl cellulose. The formulated gel was evaluated with respect to pH, in vitro gelling capacity, clarity, viscosity, in vitro  antifungal activity and in vitro transcorneal permeation behavior. The fabricated drug loaded microspheres revealed acceptable particle size, zeta potential and encapsulation efficiency. The prepared in situ  gels were clear and exhibited acceptable pH, rheological properties and in vitro  gelation. The drug loaded microsphere based gel revealed superior in vitro  antifungal activity against Aspergillus niger  than conventional formulation and sufficient drug permeation across goat cornea. Thus, formulated clotrimazole loaded microsphere based in situ gel based systems can be a promising approach for sustained ophthalmic delivery of antifungal agents.