Eco-Friendly Analytical Quality By Design-Based Liquid Chromatographic Method For Estimation Of Molnupiravir In Bulk And Pharmaceutical Formulation

Abstract

Implementation of quality by design (QbD) in developing greener analytical methods provides valuable knowledge about the use of greener chemicals and their impact on method performance.Green analytical chemistry(GAC) has mainly focussed on developing analytical methods that are safe for the environment and the analyst. The GAC works on 12 principles that mainly focus on reducing solvent usage, replacing toxic chemicals, reusing the generated waste, and avoiding unnecessary steps.The prime focus of the existing study was to develop analytical quality by design aided stability indicating green high performance   liquid chromatography(HPLC) method for estimation  of  Molnupiravir in a capsule dosage form. The critical chromatographic factors were the % of ethanol in the mobile phase, and flow rate, their overall effect on the responses like capacity factor, tailing factor and theoretical plates were studied to optimize the method. A rotatable central composite design was employed, and the optimized conditions for chromatographic separation were made with a run time of 10 minutes using Zorbax C18 column (4.6× 150 mm, 5 µm) with  0.1%acetic acid and ethanol (70:30 v/v) as components of a mobile phase, flowing at a rate of 1.0 ml/minute. Photodiode array detection was carried out at 235 nm..The retention time was found to be 4.21 min. According to the ICH guidlines, the proposed  method was validated and stress studies revealed that Molnupiravir is prone to acidic and basic stress conditions. An analytical eco-scale score evaluated the greenness profile, and a software-based evaluation Analytical Greenness metrics, which affirmed excellent greenness. The developed HPLC method is more eco-friendly and shall be adopted  in the routine quality control of Molnupiravir in a capsule dosage form