Preparation and in vitro Characterization of Porous Carrier–Based Glipizide Floating Microspheres for Gastric Delivery

Floating microspheres have been utilized to obtain prolonged and uniform release of drug in the stomach for development of once-daily formulations. A controlled-release system designed to increase residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microspheres by the emulsion solvent diffusion technique, using (і) calcium silicate (CS) as porous carrier; (ii) glipizide, an oral hypoglycemic agent; and (iii) Eudragit^® S as polymer. The effects of various formulations and process variables on the internal and external particle morphology, micromeritic properties, in vitro floating behavior, drug loading, and in vitro drug release were studied. The microspheres were found to be regular in shape and highly porous. The prepared microspheres exhibited prolonged drug release (~8 h) and remained buoyant for >10 h. The mean particle size increased and the drug release rate decreased at higher polymer concentrations. No significant effect of the stirring rate during preparation on drug release was observed. In vitro studies demonstrated diffusion-controlled drug release from the microspheres. Microsphere formulation CS4, containing 200 mg calcium silicate, showed the best floating ability (88% buoyancy) in simulated gastric fluid. The release pattern of glipizide in simulated gastric fluid from all floating microspheres followed the Higuchi matrix model and the Peppas-Korsmeyer model.

Key words: Calcium silicate, emulsion solvent diffusion method, floating controlled drug-delivery system, glipizide, microspheres.