Formulation Development and Scale-Up of Sustained Release Tablet of Metformin Hydrochloride

Abstract

Metformin hydrochloride is first line drug therapy for the patient with type 2 diabetes mellitus acts by decreasing hepatic glucose output and peripheral insulin resistance. Sustained release formulation of metformin hydrochloride based on monolithic matrix technology was developed and evaluated. Metformin hydrochloride is a highly watersoluble drug so it is suitable to develop sustained release matrix tablet. As metformin is a short acting drug, so developed formulation provides the advantages of sustained release formulations. As metformin is having absorption only in upper part of GI tract (up to jejunum), it is suitable to develop sustained release matrix tablet. The developed formulation is equivalent to marketed products in view of its’ in vitro release. The developed formulation has an additional advantage like less steps of manufacturing procedure and is therefore economical. All of which made the procedure easily amenable to mass production using conventional tablet machines. Metformin matrix tablets formulations were prepared with different compositions. Finally, one optimized formula for each, matrix tablet was selected and studied in detail. The effect of formulation variables namely, process of manufacturing, different excipients, different polymers, and concentration of polymer were studied. Metformin release was inversely proportional to the polymer concentration. Drug release from the developed formulations was independent of pH of the release medium but dependent on the agitational intensity, hardness of tablet, and surface area of tablet. Similarity factor, ƒ2 values suggest that the test and reference profile are identical. Drug release data is fitting to Korsmeyer-peppas equation that indicated the diffusion is occurs by fickian diffusion for drug release mechanism.