Development and In Vitro/In Vivo Evaluation of Floating In Situ Gelling Oral Liquid Extended Release Formulation of Furosemide

Abstract

Floating in situ gel as gastroretentive drug delivery system represents a revolution in oral controlled release dosage forms in comparison with conventional oral liquids, as it prolongs the residence time of the drugs that have narrow absorption windows in the absorptive sites like stomach or upper gastrointestinal tract by having a bulk density lower than gastric fluids and thus remains buoyant in the stomach without affecting the gastric emptying rate until the drug released slowly, continuously and completely. This study was undertaken to formulate furosemide oral solution, which undergoes gelation when it is in direct contact with gastric fluid by using primary polymer (sodium alginate) in addition to the secondary polymer (iota-carrageenan) at different concentrations. Different variables that affect drug release profile like cross linking agent, combination of polymer, gas generating agent and drug concentrations were studied to optimize the best formulation through measuring their effects on viscosity, gel strength, floating lag time and floating duration. The best formulation exhibited 94.9% release of the drug after 5 h with effective floating property. In vivo test was applied and demonstrated good indication to the gastroretentive property of the optimum formulation through its relation to the diuretic property of the drug, and it agreed with in vitro release and the proposed kinetic mathematical modeling.