Development of a Stability‐Indicating RP‐HPLC Method for the Quantification of Tolperisone Hydrochloride and Diclofenac Sodium Impurities in Drug Substances and in Combination: Implementation of Analytical Quality by Design and Degradation Kinetics

ABSTRACT Tolperisone hydrochloride and Diclofenac sodium are formulated for the treatment of musculoskeletal conditions due to their complementary muscle relaxant and anti‐inflammatory actions. Accurate impurity profiling in such formulations is essential for ensuring drug stability, safety, and regulatory compliance. Traditional analytical methods often lack sustainability and robustness. Reverse phase high‐performance liquid chromatography remains a central tool in impurity analysis, but integrating Quality by Design strategies is still under development. This study aims to develop a novel, sustainable RP‐HPLC method for impurity profiling of tolperisone hydrochloride and diclofenac sodium tablets using Quality by Design approach. Chromatographic separation was achieved using a C18 Inertsil column (250 × 4.6 mm, 5 µm). Quality by Design was employed to optimize key parameters pH and mobile phase composition, ensuring method robustness. A kinetic study of tolperisone hydrochloride degradation under basic conditions was also conducted. The method demonstrated high resolution, precision, and reproducibility across batches. Impurities were effectively separated and quantified. Kinetic analysis indicated that tolperisone hydrochloride degradation follows second‐order kinetics under basic conditions. This Quality by Design optimized, environmentally conscious RP‐HPLC offers a reliable, scalable solution for impurity profiling in complex formulations. It supports improved pharmaceutical quality control while aligning with sustainability and regulatory standards.