Purpose

Diabetes mellitus, especially type II, is one of the most common chronic diseases. Its first-line oral treatment is metformin, commonly in combination with another agent such as sitagliptin, a dipeptidyl peptidase-4 inhibitor. The commercial combination is Janumet XR 50/500 mg, in which the extended-release metformin core tablet is coated with an immediate-release layer of sitagliptin. However, the coating process with solvents and a high temperature might affect the sitagliptin properties and product quality. Hence, the present study aimed to develop bilayer matrix tablets incorporating both drugs into two separate layers, a sustained-release metformin layer, and an immediate-release sitagliptin layer.

Methods

Wet granulation and direct compression methods were used for the metformin and sitagliptin layer, respectively. The optimal formulation was selected and characterized based on the design of experiments method. In vitro release and in vivo bioequivalence studies were also conducted to compare with the reference Janumet XR 50/500 mg.

Results

The optimized formulation immediately released sitagliptin (> 95%) within 30 min at pH 1.2 and sustained the release metformin for 10 h at pH 6.8. The in vivo behaviors of the bilayer tablets were bioequivalent to the commercial product, Janumet XR 50/500 mg.

Conclusion

The bilayer tablets could provide an alternative approach for combination therapy of type II diabetes.