Development and characterization of multiparticulate system as an alternative to unit dosage forms containing drugs with diverse release profiles

Abstract

Abstract Background Currently, the Bilayer tablets, Tablet in tablet and Inlay tablets composed of Glimepiride (GMP) and Pioglitazone (PGH) as immediate release part, and Metformin (MFH) as sustained-release part are available for the treatment of type II diabetes mellitus (T2DM). In these products, there is a possibility of the incomplete release of immediate release part (GMP and PGH) due to their entrapment into high viscosity gel barrier of MFH sustained-release part when drug product comes in contact with media. Therefore, the present study was aimed to deliver the above combination drugs in the form of hard gelatin capsules (as unit dosage form) containing MFH sustained-release (MFH-SR) pellets and immediate release pellets of PGH and GMP (PG-IR). Results The MFH-SR and GP-IR pellets, prepared by extrusion and spheronization technique, were optimized based on the drug content and % cumulative drug release. The MFH-SR pellets formulation (batch A6) has shown maximum drug content, and sustained-release of MFH similar to marketed glucophage tablet while, the GP-IR pellets formulation (batch B5) has displayed maximum drug contents and immediate release of GMP and PGH; thus, these batches were considered for further characterizations. The optimized MFH-SR and GP-IR formulations have shown particle sizes of 0.23 ± 0.0010 mm and 0.35 ± 0.0018 mm, respectively. Besides, the formulations exhibited good micromeritics properties. The in vivo pharmacokinetic study in rabbits has demonstrated comparable bioavailability of the drugs from pellets and the marketed formulations following oral administration. Further, the pellets were found to be stable for 6 months at 40 ± 2 °C/75% ± 5%RH. Conclusions The study results revealed that the multiparticulate systems with varied release profiles could be a promising approach to overcome drug release issues associated with the unit dosage forms.