Leveraging Principles of QbD for Analytical Method Development and Validation for the Estimation of Eltrombopag Olamine in Tablet Dosage Forms by HPLC

Abstract

The primary objective of this study is to implicate the Quality by Design (QbD) principle to develop a simple and stability—indicating High Performance liquid Chromatography (HPLC) method for analysing and quantifying Eltrombopag olamine. Initially, a comprehensive risk assessment was conducted using an Ishikawa (fish-bone) diagram. Following this, an Analytical Target Profile (ATP) was established, with desired specification and Critical Analytical Attributes (CAAs) were identified to fulfil these requirements. Additionally, Critical Material Attributes (CMAs) and Critical Process Attributes (CPPs) were chosen, as they can influence the CAAs. Subsequently, a three-level factorial design was utilized to optimize the primary contributing factors both numerically and graphically. The validation study was performed according to International Council for Harmonisation (ICH) guidelines and forced degradation studies were performed under various stress conditions. Optimal chromatographic separation was done using a mobile phase comprising acetonitrile and water with 0.3% formic acid in both phases at a ratio of 80:20% v/v, with 1.2 mL/min flow rate and UV detection at 248 nm. The developed method exhibited high sensitivity and specificity, with a linear range of 10–70 µg/mL and a correlation coefficient (R2) of 0.9999. It demonstrated accuracy with % recovery ranging from 98–100% and the detection and quantification limits of 0.2443 µg/mL and 0.7403 µg/mL, respectively. The forced degradation studies indicated that the drug is vulnerable to all stress conditions. Overall, the developed method proves to be suitable for estimation of Eltrombopag olamine in its marketed formulation, with potential applicability for analysing it in other dosage form and various biological samples available.