Exploring Analytical Quality by Design (AQbD) Enabled RP-HPLC Method for Carvedilol

Abstract

Background: Carvedilol (CDL) is a beta-blocker that helps to lower the risk of heart attack related mortality and is used to treat congestive heart failure and excessive blood pressure. Objectives: The present study deals with the development and validation of a reverse-phase high performance liquid chromatography method for rapid and reliable analysis of CDL by utilizing the Analytical Quality by Design (AQbD) approach. Materials and Methods: Critical Analytical Attributes (CAAs) were selected based on predefined Analytical Target Attributes (ATPs). Further screening of Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) having a significant impact on assigned CAAs was done by Taguchi Design. The optimized mobile phase consists of 0.1% Orthophosphoric Acid (OPA) and methanol in a ratio of 35:65% v/v. The flow rate was maintained at 1 mL/min, the column temperature was 30ºC, and the analysis was carried out at 240 nm. Based on the results obtained, fine tuning of the CAAs was done by opting for the 3 2 -Box-Behnken design. Results: The area under the curve was found to be linear within the studied range of 5-30 µg/mL (R 2 =0.999). The retention time was found to be 4.18 min, with a sharp, well-defined peak. The percentage recovery of the drug during the accuracy study was found to be in the range between 97.06 and 99.29%. The detection and quantification limits were found to be 0.61 µg/mL and 1.86 µg/mL, respectively. Conclusion: The developed method was found to be precise with a RSD of <1%. The method can be effectively utilized for routine analysis of bulk drug and dosage forms in quality control labs.