Development and validation of QbD-Integrated sensitive RP-HPLC method for quantitation of Fenofibrate: An application in quality control

Abstract

Aim: The present study aims to develop and validate a robust, sensitive HPLC method for the estimation of fenofibrate in a gel-matrix sustained-release tablet formulation designed to prevent alcohol-induced Dose Dumping. Method: A simple, sensitive, and robust RP-HPLC method for fenofibrate was developed using a Quality by Design approach with a Box–Behnken design to optimise critical chromatographic variables and define a reliable design space. The method was validated as per International Council for Harmonisation Q2(R1) guidelines. Analysis was performed on a Shimadzu HPLC system with PDA detector, binary pump, and column oven. Optimised conditions included a 70:30 (acetonitrile:water, pH 2.5) mobile phase, flow rate of 1.2 mL/min, C18 column (150 × 4.6 mm), 8 min runtime, sample temperature of 4°C, and column temperature of 40 ± 2°C. The method was applied to sustained-release fenofibrate formulations to evaluate blend uniformity, content uniformity, assay, and dissolution under alcohol-induced dose-dumping conditions. Results: The developed method was found to be specific and sensitive, with lower limits of detection and quantitation, and linear (R2 = 0.999) over the concentration range of 5 µg/mL-80 µg/mL. The maximum absorbance was recorded as fenofibrate (λmax) 285 ± 2 nm. Compared to previously reported RP-HPLC methods (LOD: 0.14–0.9 µg/mL; LOQ: 0.45–2.7 µg/mL), the developed method demonstrated significantly improved sensitivity (LOD: 0.0438 µg/mL; LOQ: 0.132 µg/mL) and reduced retention time (~4.5 min vs 6–20 min), indicating enhanced analytical efficiency. All the validated results were within the acceptance limits. Conclusion: Our findings revealed that the developed RP-HPLC method is sensitive and robust. It was successfully employed in the quality control assessment of the laboratory-developed gel-matrix SR-oral formulation of fenofibrate, particularly under conditions that appreciate dose dumping.