Development and Evaluation of Multiparticulate Delivery System for the treatment of Type II Diabetes

Abstract

Fixed dose combination of Pioglitazone plus Glimepiride immediate release and Metformin sustained release provide loading and maintenance dose and have proven to be very effective in the management of Type 2 Diabetes mellitus (T2DM). Multiparticulate systems have the advantage of providing minimal fluctuations in plasma drug concentrations and enhancing the patient convenience and compliances in comparison to single unit dosage forms. However, till date no multiunit system containing the combination of these drugs has been commercialised. The objective of this study was to develop and compare fixed dose combination of Metformin (500 mg) as sustained release and Pioglitazone (15 mg) and Glimepiride (1 mg) as immediate release pellets with the innovator products, Glucophage Tablet 500 mg (for Metformin), Actos Tablet 15 mg (for Pioglitazone) and Amaryl Tablet 1 mg (for Glimepride). Metformin hydrochloride pellets were prepared using Carbopol 971 as hydrophilic control release polymer and microcrystalline cellulose as an extrusion spheronization aid whereas Glimepiride and Pioglitazone hydrochloride immediate release pellets were formulated using lactose monohydrate (solubilizer), microcrystalline cellulose (disintegrant) and Tween 80 (surfactant). Both, sustained as well as immediate release pellets, prepared by extrusion-spheronization technique, were found to possess drug content within 90% to 110% range of the label claimed dose. The SEM images confirmed the spherical shape of the pellets. Development involves design of experiment approach (DoE,IV-Design, Three factorial design) , where studied factors and ranges demonstrated comparable results as that of final composition, which confirms that within studied design space product showed no significant impact with respect to product quality. Dissolution of immediate release pellets exhibited of more than 80 % at 15 minutes for Glimepride and complete release at 30 minutes for Pioglitazone, which was comparable to the release provided by Amaryl and Actos release. newline