ABSTRACT:
The present study describes a Quality by Design (QbD)-driven RP-HPLC method for the simultaneous estimation of Metformin Hydrochloride (MET), Dapagliflozin (DAPA), and Vildagliptin (VILDA) in a combined dosage form. QbD offers a systematic, science-based, and risk-oriented framework for analytical method development and validation, overcoming the limitations of traditional trial-and-error approaches. The method was developed by defining an Analytical Target Profile (ATP), identifying Critical Quality Attributes (CQAs) and Critical Process Parameters (CPPs), and establishing a robust Design Space. Box-Behnken Design (BBD) was employed to explore the effect of independent variables such as mobile phase composition, flow rate, and column temperature on method performance. The desirability function was applied to simultaneously optimize retention time and resolution of the three analytes. The isosbestic point for MET, DAPA, and VILDA was found at 209nm and was utilized during experimental design. The optimized chromatographic conditions included Methanol: 10mM KH2PO4 buffer (80:20 v/v), a flow rate of 0.8mL/min, and ambient column temperature, yielding effective baseline separation. The method was validated as per ICH Q2 guidelines, confirming its precision, accuracy, specificity, and robustness. Thus, the QbD approach proved highly effective in developing a reliable and efficient RP-HPLC method for simultaneous drug estimation.