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.

Floating Microspheres of Enalapril Maleate as a Developed Controlled Release Dosage Form: Investigation the Effect of Ionotropic Gelation Technique

“…This was due to the immediate crosslinking of microspheres matrix as an outcome of strongly acidic sulfate groups in iota carrageenan molecule that allows a certain degree of polymer ionization in (0.1 N HCl, pH 1.2) leading to the formation of insoluble gel-like layer of aggregated double-helical segments that form a three-dimensional network by complexation, and consequently slower solvent penetration into the matrices and more controlled CO2 diffusion was achieved and thus inducing the microspheres to float rapidly. 55 While a further increment of iota carrageenan concentration as shown in F5 will lead to a decrease of buoyancy effect. This was related to the increment of iota-carrageenan viscosity as the concentration raised.…”

“…The gel matrix will swell and withstand erosion under acidic conditions to maintain a constant diffusion path length; forming a highly crosslinked matrix with minimum porosity. 55…”

Preparation, in vitro and in vivo Characteristics of Floating in situ Gel of Carvedilol Using Semi Synthetic and Natural Polymers to Enhance the Oral Bioavailability

“…The naked eye was used to check the clarity of all the prepared in situ gel using the black and white background. 30,31…”

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“…At the free end of the device a lightweight pan (3 g) was attached to which the weights were added. The gel strength was reported in terms of weight required to pass the apparatus through the formed gel mass 17,18 .…”