QUALITY BY DESIGN (QbD) APPROACH FOR METHOD DEVELOPMENT FOR AZILSARTAN MEDOXOMIL USING UPLC: APPLICATION TO HYDROLYTIC, THERMAL AND OXIDATIVE DEGRADATION KINETICS

Quality by Design (QbD) is a systematic approach for the development of products and processes. Azilsartan Medoxomil is a competitive antagonist of the Angiotensin II Type 1 receptor. A precise and reproducible ultra-performance liquid chromatographic (UPLC) method was developed and validated for the estimation of Azilsartan Medoxomil from its marketed tablet dosage form applying Quality by Design approach. Eight experiments were conducted using the full factorial design in order to rationally examine the effects of stationary phase, buffer pH and organic phase concentration in primary screening followed by method optimization with variation in Column temperature and flow rate. Chromatographic separation of AZIL was achieved at 40 °C temperature using an Acquity UPLC BEH C18 (4.6mm × 2.1mm, 1.7μ) analytical column; the mobile phase consisted of Acetonitrile: phosphate buffer (pH 5.5, 0.02mM) (40:60, v/v) at a flow rate of 0.3 ml min^-1. Azilsartan eluted with retention time (Rt value) 2.41 min. The linear regression analysis showed good linear relationship with a correlation coefficient of 0.999. The limit of detection and quantitation were found to be 0.171μg/ml and 0.57μg/ml, respectively. The method was validated as per ICH guidelines. Exposure of analyte to different stress conditions showed that AZIL follows second order reaction in both acidic and basic medium and first-order reaction in peroxide medium with rate constant 7.351× 10^-3 mol L^-1 s^-1, 7.427 × 10^-3 mol L^-1 s^-1 and 1.277× 10^-2 mol L^-1 s^-1 respectively. The method developed is a stability-indicating, robust, simple, accurate, and reproducible for the determination of AZIL in bulk and formulation.