FORMULATION DEVELOPMENT AND CHARACTERIZATION OF MULTIPLE LAYER TABLETS OF IMMEDIATE RELEASE SITAGLIPTIN AND EXTENDED RELEASE METFORMIN

Abstract

The management of type 2 diabetes mellitus often necessitates combination therapy, which can increase treatment complexity and reduce patient compliance. Fixed-dose combination (FDC) tablets of sitagliptin and metformin offer a practical solution but are often associated with high production costs and formulation challenges. This study aimed to develop cost-effective multilayer tablets combining immediate-release (IR) sitagliptin and sustained-release (SR) metformin, and to evaluate final product performance in terms of critical parameters.

Six formulations were prepared, four bilayer and two trilayer tablets using wet granulation and direct compression techniques. Pre-formulation studies confirmed satisfactory flow and compressibility. All formulations passed standard physical and chemical quality tests. Sitagliptin showed >85% release within 30 minutes, meeting IR criteria. Metformin release was sustained over 12 hours, with trilayer formulations (F5, F6) closely matching the reference product, Janumet XR®.

Comparative dissolution testing using model-independent (ƒ1 and ƒ2) and model-dependent (zero-order, Higuchi, and Korsmeyer–Peppas) approaches identified F1, F5, and F6 as pharmaceutically equivalent to the innovator product. These formulations followed zero-order release kinetics and anomalous non-Fickian diffusion, indicating controlled and predictable drug release. Stability testing under ICH conditions demonstrated no significant changes in drug content or dissolution behavior over six months.

In conclusion, the optimized multilayer tablet formulations (F1, F5, F6) offer a robust, scalable alternative to existing FDC products, with potential for local use and export market.