Controlling Release of Metformin HCl through Incorporation into Stomach Specific Floating Alginate Beads

Abstract

The aim of present study was to develop stomach specific floating beads of metformin hydrochloride for effective management of type 2 diabetes mellitus. The beads were evaluated for surface morphology, particle size, tapped density, true density, percent porosity, drug entrapment efficiency, percent yield, differential scanning calorimetry, in vitro floating ability and in vitro drug release. Stability studies were performed at 25 and 40 °C up to 45 days. Effectiveness of the formulations was evaluated in vivo by hypoglycemic response in both normal and diabetic albino rats. The beads were grossly spherical in shape, and average particle diameter of beads was found to be in the size range of 861.34 to 991.75 μm. Percent entrapment was found to be in the range of 77.61 to 82.48%. Beads demonstrated favorable in vitro floating ability. All the formulations followed a non-Fickian release mechanism. It was found that there was no significant effect on floating ability of aged beads since it floated up to an 8 h study period. In vivo studies on diabetic rats showed that the hypoglycemic effect induced by the metformin hydrochloride loaded alginate beads was significantly greater (P < 0.05) and more prolonged than that induced by the nonfloating beads. The results clearly demonstrated the ability of the formulation to maintain blood glucose level and improved the patient compliance by enhancing, controlling and prolonging the systemic absorption of metformin hydrochloride.

In vitro and in vivo evaluation of alginate and alginatechitosan beads containing metformin hydrochloride

“…It was observed that the degree of swelling of AL beads increased with increase of pH of release medium, probably due to exchange of the Ca 2+ ion with Na + . These results are in agreement with the results of previous studies [11,15]. Various approaches (chemicals, dietary manipulation, or surgery) are available in the literature for development of experimentallyinduced type 2 diabetes.…”

“…On the other hand, the fasting blood glucose levels of metformin HCl-loaded AL-CS and AL beads gradually declined and peaked in 6 hr and 4 hr, respectively, indicating that hypoglycaemic effect was extended by both bead formulations. Similar observations are reported in the literature [15,32]. Nayak et al [15] evaluated the hypoglycaemic effects of nonfloating and floating alginate beads containing metformin HCl on STZ-induced diabetic rats and found that a significant hypoglycaemic effect was obtained for floating beads 3 to 9 hr after bead administration.…”

“…Similar observations are reported in the literature [15,32]. Nayak et al [15] evaluated the hypoglycaemic effects of nonfloating and floating alginate beads containing metformin HCl on STZ-induced diabetic rats and found that a significant hypoglycaemic effect was obtained for floating beads 3 to 9 hr after bead administration. However, this effect was visible up to 5 hr after the administration of non-floating beads.…”

“…It has cationic character due to its primary amino groups and thus, shows muco-adhesive properties. AL beads and CS beads containing metformin HCl were prepared in previous studies [14,15]. In our study, besides metformin HClloaded AL beads, we also prepared AL-CS beads containing metformin HCl using AL and CS combination.…”

“…In our study, besides metformin HClloaded AL beads, we also prepared AL-CS beads containing metformin HCl using AL and CS combination. CS and AL are very useful in pharmaceutical applications and they are the most widely used hydrogels in the preparation of sustained release dosage forms [11,15,16].…”