Stability indicating Analytical Method Development using Quality by Design (QbD) approach for simultaneous estimation of Ivabradine and Metoprolol

Abstract

The applicability of a quality by design (QbD) approach for the development of a sensitive and selective stability indicating reversed-phase high performance liquid chromatography (RP-HPLC) method for the estimation of Ivabradine and Metoprolol was investigated. Design of experiments using a fractional factorial design approach was used for method development. Fifteen experimental runs were performed to optimize the chromatographic conditions like mobile phase, flow rate and column oven temperature. Mobile phase composition was optimized by changing Acetonitrile composition ranging between 13 and 17% v/v, Flow rate from 0.6 to 1.0 ml/min and temperature between 30 to 50 0C. The optimized method produced sharp peaks with good resolution (>2) for Metoprolol and Ivabradine with retention times of 3.3 and 9.2 min, respectively. The experimental data revealed that volume of Acetonitrile in mobile phase was prominently affecting the Retention time, Resolution & tailing factor of both the drugs. Normal probability plots revealed that the residual and predicted data fall approximately on a straight line, indicating that the experimental error for these studies was evenly distributed suggesting that the model could be used to navigate the design space. This approach is useful to expedite method development and optimization activities in analytical laboratories.