Effervescent floating tablets of metformin HCl developed by melt granulation. Part I: Effect of hydrophilic polymer on biopharmaceutical properties

Abstract

In the present study which the aim to evaluate the effect of hydrophilic polymer on the biopharmaceutical properties of metformin hydrochloride floating tablets, we have prepared floating systems using melt granulation, according to effervescent approach. Two hydrophilic polymers are used at various concentrations (10, 12.5, 15 and 17.5%), Acacia gum and hydroxypropylmethylcellulose (HPMC) at three viscosity grades (K4M, K15M and K100M). In addition to the satisfactory physical parameters, the evaluation of buoyancy and in vitro dissolution of floating developed systems revealed that the biopharmaceutical performances of these systems depended on the nature of the polymer. Unlike the acacia gum which did not produce floating systems, the HPMC matrixes had good buoyancy properties: fast buoyancy time (240±30 to 360±30 sec) and total flotation time more than 24 hours with matrix maintained integrity. In addition, in the case of HPMC, a significant influence of viscosity grade on MTH kinetics has been demonstrated. Indeed, the observed results showed that at 17.5% of HPMC, as the viscosity grade increases, the dissolution kinetics of metformin HCl was extended. The formulations F8 (HPMC K15M) and F12 (HPMC K100M) have exhibited the drug release rates of about 92 and 80% respectively at the end of 8 hours dissolving. These formulations followed Korsmeyer-Peppas/Higuchi release kinetics according to a Non-Fickian mechanism. Finally, the melting granulation process of MTH with stearic acid, in the case of HPMC K100M, used at high concentration (17.5%), has allowed the development of extended-release effervescent floating tablets (> 8 h).