Design of Experiments (DoE) - Based Enhanced Quality by Design Approach to Hydrolytic Degradation Kinetic Study of Capecitabine by Eco-friendly Stability Indicating UV-Visible Spectrophotometry

Capecitabine is an anti-metabolite class of anti-neoplastic drug that is converted to fluorouracil in body tissue. Numbers of stability indicating chromatography method such as HPLC, HPTLC etc. have been reported for stability study of capecitabine. But the chromatography methods are tedious, time and solvent consuming methods. Hence, stability-indicating UV-visible spectroscopy method has been developed for hydrolytic degradation kinetic study of capecitabine using design of experiments (DoE)-based enhanced quality by design approach (QbD) to save time, solvent and cost of analysis. The potential method parameters were identified and assessed by risk priority number (RPN) ranking and filtering. The DoE-based full factorial designs were applied for degradation kinetic study in alkaline and acidic medium at different temperature. The rate constant, order of reaction, half-life and % degradation of capecitabine was calculated. The absorbencies of all samples were measured at 307nm wavelength and linearity of capecitabine was found to be in the range of 5-25µg/mL. The order of reactions for alkaline and acidic degradation kinetic was found to be first order. The highest degradation rate constant and % degradation of capecitabine was found to be in 0.3 N acid or base at 50?C. The prediction of rate constant and % degradation of capecitabine was done using DoE-based response surface analysis. The data of degradation kinetic was found to be in good agreement with published RP-HPLC method of capecitabine.