FORMULATION AND OPTIMIZATION OF CONTROLLED RELEASE FLOATING MICROSPHERES OF FUROSEMIDE FROM ETHYLCELLULOSE AND HYDROXYPROPYL METHYLCELLULOSE POLYMER BLENDS

Furosemide is a potent and commonly used loop diuretic. It is absorbed largely in the stomach and upper small intestine. This narrow absorption window results in its low (average of 50%) and variable (10-100%) bioavailability from conventional dosage forms. The objective of the present study was to develop an optimized controlled release floating microspheres of furosemide capable of floating on the gastric fluid and delivering the drug over a period of 12 h. The floating microspheres were prepared by solvent evaporation method. Preliminary studies were conducted and, drug loading and EC/HPMC ratio were identified as the most important factors affecting the desired response variables: drug release rate and buoyancy. The effects of drug loading and EC/HPMC ratio were further studied and optimized. Simultaneous optimization of buoyancy and release rate was performed using central composite design and the most desirable optimal point was obtained at release rate of 27 h^-1/2 and buoyancy of 58.45%, with corresponding levels of 344 mg furosemide and 4.84 EC/HPMC ratio. Evaluation of the optimized formulation showed high yield, good flow property, extended release and buoyancy over a period of 12 h and excellent drug entrapment efficiency. Comparison of the release profiles of the three different batches of the optimized formulation confirmed that there was no statistically significant difference (p = 0.302) in the release profiles of the formulations.