Optimization of Anti-Diabetic Bilayer Tablets Employing the Concept of Quality-By-Design

Abstract

This study aimed to optimize the formulation of a bilayer tablet containing a fixed-dose combination (FDC) of a biguanide and a dipeptidyl peptidase-4 (DPP-4) inhibitor, classified as BCS Class III and I borderline. The treatment of type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to insulin secretion or action abnormalities. It has a sustained-release layer for the high-dose drug and an immediate release layer for the low-dose drug. Purity of the active pharmaceutical ingredient (API) was performed using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Preliminary trials for the sustained-release layer were formulated by wet granulation with different polymers, such as HPMC K100M CR and HPMC K15M. One-factor-at-a-time (OFAT) trials were carried out for the immediate release layer, and optimization was achieved through this method. These polymers were incorporated intra-granularly and extra-granularly, and concentrations were optimized based on hardness, assay, drug release, thickness, and friability. A 32 full factorial design was employed, with polymer HPMC K100M CR (X1) and binder PVP K30 concentration (X2) as independent factors at three levels (+1), (0), and (-1) and response variables as drug release and hardness. The optimal polymer concentration yielded a drug release profile similar to that of the reference listed drug (RLD) with optimal hardness. The polymer demonstrated a drug release profile similar to and more effective than the RLD polymer. Employing the concept of quality-by-design (QbD) and optimization using DOE software enabled the formulation of the FDC bilayer tablet, enhancing quality, safety, and efficacy over traditional methods.