INTEGRATION OF BOX–BEHNKEN DESIGN AND QBDPRINCIPLES FOR OPTIMIZING RP-HPLC ANALYSIS OF IMEGLIMIN HYDROCHLORIDE

Abstract

The development and validation of analytical methods are critical components in ensuring thequality, safety, and efficacy of pharmaceutical products. This study presents a comprehensiveapproach to developing and validating an analytical method for Imeglimin Hydrochloride, a novelanti-diabetic agent with a unique dual mechanism targeting mitochondrial bioenergetics. Emphasisis placed on the integration of Quality by Design  principles to enhance method robustness, accuracy,and reproducibility.A systematic approach was adopted for method development utilizing reverse-phase high-performance liquid chromatography (RP-HPLC). The Box-Behnken Design was utilizedto optimize critical method parameters, and method validation was conducted in accordance withthe ICH Q2 (R1) guidelines. The developed methods were systematically evaluated for linearity,accuracy, precision, specificity, robustness, ruggedness, and stability.The HPLC method, employinga mobile phase consisting of methanol and water in a 60:40 (v/v) ratio, demonstrated excellentsystem suitability and precision, with detection performed at 239 nm.  Method is effectively used toassay marketed formulations, validating their suitability for routine quality control. Furthermore,risk assessments and Quality by Design tools such as design space and control strategies wereemployed to ensure method reliability throughout the drug’s lifecycle. This work highlights thesignificance of adopting a science-based and regulatory-compliant strategy for analytical methoddevelopment, particularly for novel pharmaceutical compounds like Imeglimin Hydrochloride. Thevalidated methods offer reliable tools for quality assurance in both research and industrial settings,supporting regulatory submissions and advancing diabetes therapeutics