Design, development and scale up studies of metformin hydrochloride multiparticulate system: A promising alternative to large size tablet

Abstract

Metformin hydrochloride (MH) is prescribed for treating diabetes mellitus. The most popular dosage form, viz., tablets has a bulky nature as MH dose ranges up to 1000 mg leading to large size. In geriatric or dysphagic patients, due to altered physiology, swallowing such bulky formulation is troublesome. Thus, this study aims towards formulation of palatable multiparticulate system in the form of pellets, which are presented in unit sachets, in the dose of 1000 mg and 500 mg. These pellets in sachets can be substituted for bulky tablets. The main challenge of this study was to mask the bitter taste of MH, which could be achieved by applying a coat of sweetener to the pellets. The formulation was optimized using 23 factorial design. Povidone as a binder, quantity of sucralose in coating and amount of coating over pellets were considered as independent factors at two levels. The pellets were evaluated for surface texture, bulk density, sweetness, dissolution and assay. Their manufacturing process was scaled up at 50X level compared to the laboratory batch size. The stability studies were conducted as per the ICH guidelines using 3 ply sachets (12 μm polyester/9 μm aluminium/63 μm polyethylene). The optimized formulation was free flowing having a sweet and pleasant taste, exhibited acceptable compliance with the quality standards. The formulations were found stable for 6 months at accelerated conditions and 12 months at the room temperature during stability study. Hence, the present work can provide an alternate option for better patient compliance.