Development and validation of a stability indicating chromatographic methods for simultaneous estimation of selected drugs in their dosage forms using doe approach

Abstract

The applicability of a quality by design (QbD) approach for the development of sensitive and selective stability-indicating chromatographic methods for simultaneous estimation of Ivabradine and Metoprolol in their combined dosage form and Budesonide and Levosalbutamol in their combined dosage form were investigated. Design of experiments was used for method development. Fractional Factorial Design was used to optimize the chromatographic conditions for HPLC and HPTLC method for Ivabradine and Metoprolol Combination. Central composite design (CCD) was used to optimize the chromatographic conditions for the HPLC method of Budesonide and Levosalbutamol combination. Box-Behnken design was used to optimize the chromatographic conditions for the HPTLC method of Budesonide and Levosalbutamol combination. The optimized methods (HPLC and HPTLC) for both the combinations produced sharp peaks with good resolution (gt2). Significant degradation was obtained after acidic and basic hydrolysis and in Oxidation condition for Ivabradine and Metoprolol. One Major impurity of Ivabradine was isolated and identified using mass spectroscopy. Significant degradation was obtained after acidic and basic hydrolysis for Budesonide, and in acidic hydrolytic condition for Levosalbutamol. This approach can be applied to expedite method development and optimization activities in analytical laboratories. newline newline