Novel Bioequivalent Sitagliptin and Metformin Bilayer Tablet with Improved Chemical Stability

Objectives: Fixed-dose combination tablets containing sitagliptin hydrochloride (SG) and metformin hydrochloride (MF) are a mainstay in the clinical management of type 2 diabetes. However, SG is highly susceptible to chemical degradation during storage, particularly in the presence of MF. Herein, a bilayer tablet in which SG and MF are physically separated into distinct layers was designed to enhance the chemical stability of SG while ensuring pharmacokinetic equivalence to the marketed reference product Janumet®. Methods: The compositions of individual SG and MF compartments were selected based on evaluations of their physical properties and dissolution profiles. Critical process parameters, including the pre- and main compression forces and coating levels of bilayer tablets, were fine-tuned to achieve dissolution characteristics comparable to those of the reference product. Results: Under accelerated storage conditions (40 °C, 75% relative humidity), the optimized bilayer tablet exhibited superior stability, with total SG-related impurity levels of 0.18% compared with 0.86% in the reference product after six months. Furthermore, in a randomized bioequivalence study in healthy volunteers (n = 30), the SG/MF bilayer tablet was pharmacokinetically equivalent to the reference product, with all parameters falling within the Food and Drug Administration-mandated regulatory criteria. Conclusions: In conclusion, this SG/MF bilayer tablet has better storage stability than the reference product and may be an alternative to conventional SG/MF combination tablets.