QbD-based development and AGREE-guided validation of a stability-indicating RP-HPLC method for Tafamidis Meglumine in bulk drug and formulation

Abstract A Quality by Design (QbD) is a systematic approach to ensure product quality by understanding critical factors, variables, and their interactions through well-planned studies and controlled processes. Three essential elements of the RP-HPLC method viz. mobile phase composition, column temperature, and flow rate were used in the Box-Behnken design of the factor screening investigations. Herein, a stability-indicating RP-HPLC method was developed and validated for quantifying Tafamidis Meglumine in bulk drugs and pharmaceutical formulations. The method demonstrated robust performance and environmental sustainability, as evidenced by a favourable AGREE score of 0.83. Methanol was used as the solvent for its excellent solubilizing properties, and chromatographic separation was achieved on a Qualisil BDS C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase of 0.1% ortho-phosphoric acid in methanol and acetonitrile (50:50 v/v ) at a flow rate of 1.0 mL/min and detection at 309 nm. The method exhibited a sharp, symmetrical peak with a retention time of 5.02 ± 0.25 min. Validation followed ICH Q2(R1) guidelines, demonstrating excellent linearity over 2–12 µg/mL (R² = 0.9998), high sensitivity with LOD and LOQ of 0.0236 µg/mL and 0.0717 µg/mL respectively, and accuracy with recovery rates between 98.5% and 101.5% (%RSD < 2%). The forced degradation studies under acidic, alkaline, oxidative, photolytic, and thermal conditions confirmed the method’s stability-indicating capability by effectively separating Tafamidis Meglumine from its degradation products. The method’s novelty lies in its simple solvent system, avoiding buffers and hazardous reagents, and its successful application to an in-house capsule formulation highlights its suitability for routine quality control and stability studies. Graphical abstract