Abstract

Metformin hydrochloride is recommended globally as first line therapy due to its favorable profile on morbidity and mortality associated with type-2 diabetes mellitus. However, limitations of multiple dosing and risk of triggering gastrointestinal symptoms make its dose optimization difficult. The present study was designed to develop the oral sustained release metformin hydrochloride tablet formulation using lipophilic waxes viz. hydrogenated castor oil, stearic acid and glyceryl monostearate either alone or their combinations. The in vitro dissolution study was carried out using USP 22 apparatus I, basket method. The drug release kinetics demonstrated that hydrogenated castor oil sustained the release of metformin greater than stearic acid and glyceryl monostearate when used alone. Combination of hydrogenated castor oil with stearic acid (1:1) sustained the drug release (75.69 ± 0.76%) greater than hydrogenated castor oil with glyceryl monostearate (86.45 ± 0.96%) and stearic acid with glyceryl monostearate (92.29 ± 0.76%) combinations. Kinetic modeling of in-vitro dissolution profiles revealed that metformin release ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport mechanisms. Applying Korsmeyer equation to in-vitro drug release data indicated that diffusion along with erosion could be the mechanism of drug release.

Key words: Hydrogenated castor oil, stearic acid, glyceryl monosterate, metformin matrix tablet, release kinetics.