Spectrophotometric Analysis of Favipiravir Using Hydrotropic Solubilization Technique: Method Development and Validation

Abstract

Background: Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide) is a broad-spectrum antiviral agent approved for the treatment of influenza and repurposed for COVID-19 management. It is classified as slightly soluble in water, and most reported analytical methods for its estimation employ expensive and potentially toxic organic solvents. Hydrotropic solubilization is an eco-friendly, cost-effective technique that enhances aqueous solubility of poorly water-soluble drugs without organic solvents, offering a greener alternative for routine analytical applications. Aim: To develop and validate a simple, eco-friendly, and cost-effective UV spectrophotometric method for the estimation of Favipiravir in pure and pharmaceutical formulations using sodium salicylate as a hydrotropic solubilizing agent. Materials and Methods: Preliminary solubility studies were performed in distilled water and various hydrotropic agents (sodium benzoate, sodium salicylate, urea, sodium citrate, and sodium acetate) at concentrations of 0.2 M, 0.4 M, 0.6 M, 0.8 M, and 1.0 M. Sodium salicylate (0.2 M) was selected as the optimal hydrotrope based on maximum solubility enhancement. UV spectrophotometric analysis was performed using a Jasco V-630 double beam spectrophotometer at the wavelength of maximum absorption (λmax = 324 nm). The developed method was validated as per ICH Q2(R1) guidelines for linearity, accuracy, precision, ruggedness, robustness, limit of detection (LOD), and limit of quantitation (LOQ). Results: The method demonstrated excellent linearity in the concentration range of 0.3–1.8 µg/mL with a correlation coefficient (r²) of 0.9959 and a regression equation of Y = 0.5115x + 0.0436. Accuracy studies showed percentage recovery in the range of 97.77–100.72%. Intraday and interday precision studies yielded %RSD values of 0.09% and 0.65%, respectively. The LOD and LOQ were determined to be 0.067614 µg/mL and 0.20489 µg/mL, respectively. Ruggedness studies between two analysts showed %RSD values of 0.62% and 0.43%, and robustness studies with wavelength variation (±2 nm) demonstrated %RSD values ranging from 0.01–1.071%. Conclusion: A novel, simple, precise, accurate, eco-friendly, and cost-effective UV spectrophotometric method was successfully developed and validated for the estimation of Favipiravir using 0.2 M sodium salicylate as a hydrotropic solubilizing agent. The method eliminates the need for costly and hazardous organic solvents and can be employed for routine quality control analysis of Favipiravir in bulk and pharmaceutical formulations.