Generation of predictive models for oxidative degradation kinetics of dapagliflozin with the applications of DOE and stability indicating HPLC method

Abstract

AbstractApplying kinetics principles to drug degradation studies helps in determine the expiration dates of drugs and formulations. An accurate, precise and sensitive stability‐indicating high‐performance liquid chromatographic method was developed and validated to study the degradation kinetics of Dapagliflozin (DGZ). DGZ was degraded under different stress conditions and degraded samples were chromatographed on C18 (150 mm × 4.6 mm, 5 µm) column, separated using solvent system acetonitrile and 0.01% triethylamine solution (pH 5 adjusted with orthophosphoric acid) in a ratio of 70:30 v/v and detected at 270 nm. The design of experiments (DOEs) was applied to study the degradation kinetics of DGZ in the oxidative medium. The effect of temperature and concentration of H2O2 on the order of reaction and % degradation was studied at three levels using a full factorial design. The linearity range for DGZ was 1–60 µg/mL (correlation coefficient = 0.9996) with an average recovery of 99.98%. The limit of detection (LOD) and limit of quantitation (LOQ) for DGZ were 0.07 and 0.22 µg/mL, respectively. Degradation of DGZ in the oxidative medium was found to follow first‐order kinetics. Contour plots have been generated to predict the degradation rate constant and % degradation of DGZ in different combinations of temperature and concentration of H2O2 using Design Expert software (Trial version).