QbD-Enabled Development and Validation of a Liquid Chromatographic Method for Estimating Galantamine Hydrobromide in Biological Fluids

Background: Analytical method development and validation remain the key prerequisites for the successful development of a product. Methods: An endeavour, therefore, was made for the development of an effortless, swift, sensitive and cost-effective method for estimation of galantamine hydrobromide using the established paradigms of Quality by Design (QbD). Results: Chromatographic separation was accomplished on a reverse phase C18 column employing an optimized mixture of methanol, acetonitrile and ammonium formate buffer, adjusted to pH 9, at a flow rate of 0.7 mL/min with UV detection at 212 nm. At the onset, risk assessment and factor screening studies using Taguchi design facilitated the understanding of the factors that are crucial in varying Critical Analytical Attributes (CAAs). The mobile phase ratio and the flow rate through the column were identified as the Critical Method Parameters (CMPs), and were subsequently employed for systematic method optimization using a Face-Centred Cubic Design (FCCD), employing four Critical Analytical Attributes (CAAs) viz. retention time, peak area, peak tailing and theoretical plates. Statistical modeling was accomplished, followed by response surface analysis leading to complete analytical understanding and comprehending plausible interaction(s) among CMPs, if any. Numerical and graphical optimizations were employed in order to demarcate the design space and eventually search for an optimum solution. Conclusion: The studies successfully reveal the utility of analytical QbD (AQbD) paradigms for developing quite sensitive and precise liquid chromatographic method, for galantamine hydrobromide, with enhanced method performance and improved analytical understanding.