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

Abstract

The development and validation of analytical methods are critical components in ensuring the quality, safety, and efficacy of pharmaceutical products. This study presents a comprehensive approach to developing and validating an analytical method for Imeglimin Hydrochloride, a novel anti-diabetic agent with a unique dual mechanism targeting mitochondrial bioenergetics. Emphasis is 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 utilized to optimize critical method parameters, and method validation was conducted in accordance with the ICH Q2 (R1) guidelines. The developed methods were systematically evaluated for linearity, accuracy, precision, specificity, robustness, ruggedness, and stability.The HPLC method, employing a mobile phase consisting of methanol and water in a 60:40 (v/v) ratio, demonstrated excellent system suitability and precision, with detection performed at 239 nm. Method is effectively used to assay marketed formulations, validating their suitability for routine quality control. Furthermore, risk assessments and Quality by Design tools such as design space and control strategies were employed to ensure method reliability throughout the drug’s lifecycle. This work highlights the significance of adopting a science-based and regulatory-compliant strategy for analytical method development, particularly for novel pharmaceutical compounds like Imeglimin Hydrochloride. The validated methods offer reliable tools for quality assurance in both research and industrial settings, supporting regulatory submissions and advancing diabetes therapeutics