PREPARATION AND EVALUATION OF ONCE-DAILY FLOATING GMO-ALGINATE MICROSPHERES CONTAINING FAMOTIDINE

Abstract

Objective: In this work, a gastro-retentive floating microsphere delivery system composed of Drug/Glyceryl mono-oleate (GMO) embedded in a Ca-alginate gas-generated matrix was designed to improve the bioavailability of a slightly-soluble model drug Famotidine. Methods: The water/Oil emulsion method was used to prepare Famotidine floatable microspheres, and formulation variables such as Alginate: GMO ratio, gas-generated bicarbonates concentration, and loading drug concentration were investigated. Conventional techniques, including DSC, XRD and FTIR were performed to confirm Famotidine compatibility with GMO and Alginate polymers. Real-Time X-ray Radiography was used for in vivo imaging of Famotidine floatable microspheres using rabbits as an animal model. HPLC spectroscopic technique was used to determine Famotidine plasma concentration after oral administration of Alginate-GMO loaded microspheres. Results: Floating Famotidine Alginate-GMO microspheres (0.75:1:0.25) w/w/w showed a remarkable entrapment efficiency (>98%), good buoyancy (>84) and prolonged in vitro drug release properties (>24 hours). DSC, XRD, and FTIR techniques showed no evidence of interaction between Famotidine and Alginate or GMO. In vivo Imaging of Famotidine floatable microspheres showed that capsules containing Famotidine-Alginate microspheres were not detected after 3 h of administration, while capsules containing Famotidine-GMO-Alginate microspheres can be detected for more than 12 h, indicating superior gastric retention properties. The pharmacokinetic parameters were calculated for Famotidine: GMO-Alginate, and Famotidine: alginate and compared with the plain drug over 24 h period. Famotidine: GMO-Alginate microspheres exhibited controlled and prolonged absorption Tmax of 6.0 vs. 3.0 and 2.0 h; Cmax of 124.9±0.9 vs. 323.7±0.4and 458.6±0.5 ng/ml; AUC0-24 of 2153.025±6.7 vs. 1650.4±1.9 and 1110.725±2.1 ng/ml for Famotidine: alginate and plain drug, respectively, reflecting the increase in the bioavailability of the drug in the floating formulations compared to the free drug. Conclusion: Prolonged gastric retention time and sustained release properties of floating GMO-alginate microsphere suggest that it could provide a valuable sustained release dosage form of slightly-soluble drugs.