QbD-Optimized RP-HPLC Method Development for Simultaneous Quantification of Pregabalin and Duloxetine Hydrochloride

Quality by design (QbD) is a systematic approach focused on achieving consistent, predictable quality based on predefined objectives. Unlike traditional methods, QbD prioritizes risk assessment and management, which significantly enhances the robustness of the analytical method. In this study, we initiated factor screening using a three-factor, two-level design to evaluate three independent variables: flow rate, pH, and mobile phase composition. To further investigate the interaction of these variables, we employed Central Composite Design (CCD). This allows us to apply response surface methodology to the Critical Analytical Attributes (CAAs), specifically retention time, peak area, and symmetry factor, by conforming to the method’s robustness. The combination of pregabalin and duloxetine hydrochloride (HCl) dosage form was determined using a straightforward, exact, specific, and accurate reverse-phase HPLC approach. The results showed retention times of 3.265 min and 4.318 min for duloxetine HCl and pregabalin, respectively. Pregabalin demonstrated linearity from 100 to 200 μg/mL (R2 = 0.998), whilst duloxetine HCl demonstrated linearity between 20 and 120 μg/mL (R2 = 0.997). Lower LOD values of 0.925 µg/mL and 0.853 μg/mL and LOQ values of 2.809 μg/mL and 2.587 μg/mL of pregabalin and duloxetine HCl, respectively, suggest good sensitivity for the technique. The drug content of the commercial formulation may thus be determined using the recommended method. This technique can be used for standard quality control studies to simultaneously estimate pregabalin and duloxetine HCl. The novelty of the present studies lies in the development of a robust RP-HPLC method for simultaneous estimation of pregabalin and duloxetine HCl using a systematic AQbD approach, enhancing robustness, reproducibility, and reliability, making it highly suitable for routine quality control and regulatory applications.