Development and Optimization of Stability-Indicating Method of Solifenacin Succinate and its Main Product of Degradation in Tablet Dosage form using the Quality by Design Approach

This work presents the development and optimization of the stability-indicating method for solifenacin succinate and its main degradation product, formed through oxidation, using the high-performance liquid chromatography technique with diode array detection using the quality by design approach. In this work, a forced degradation study was performed to evaluate the potential degradation profile of the active ingredient, solifenacin succinate. Here, multiple optimizations of the extraction procedure are proposed. Often, the prescribed procedure focuses on recovering the active pharmacological ingredient while neglecting the recovery of impurities, a critical step in the development of stability-indicating methods. In this step, an experimental design of mixtures using the simplex model was used in order to optimize the recovery of the active ingredient and its main degradation product. Mixture solvents were evaluated by combining water (0–40%), acetonitrile (0–100%), and ethanol (0–100%) using the ultrasound-assisted extraction technique, with evaluation times set at 10 and 30 min. The highest values were obtained using a solvent mixture of acetonitrile and ethanol in a ratio of 90 : 10 (v/v), along with a 30-minute ultrasound-assisted extraction. These recovery values exceeded those of the control condition. The development of the chromatographic method was carried out from a screening step based on the conditions reported in the literature. Subsequently, it was submitted to an optimization step where the possible analysis time was significantly reduced without loss of chromatographic efficiency. The optimal condition obtained was on the Xbridge chromatographic column with dimensions of 250 × 4.6 mm and 5 μm particle size. The system operated in gradient mode using a mobile phase containing a phosphate buffer (pH 6.7), with 0.5% diethylamine and acetonitrile in a ratio of 85 : 15 (v/v). Another mobile phase contained a phosphate buffer (pH 6.7) with 0.5% diethylamine and acetonitrile in a ratio of 20 : 80 (v/v). The temperature of the chromatographic column was maintained at 40°C, with a mobile phase flow rate of 1.1 mL/min and an injection volume of 10 μL in a gradient elution mode. The developed method was applied to evaluate the degradation profile of commercially purchased drugs.