Quality by design approach to method development and validation for quantitative estimation of dapagliflozin and linagliptin in pharmaceutical tablet dosage forms

Objectives: The present study utilizes a quality by design approach to develop a simple, robust, and stability-indicating high-performance liquid chromatography method for quantifying dapagliflozin (DAPA) and linagliptin (LINA) in a fixed-dose combination and validate it according to the ICH-Q2 (R1) guidelines. Materials and Methods: The effect of critical method parameters (CMPs), namely percentage of acetonitrile (ACN), pH of the buffer, and flow rate, on critical quality attributes (CQAs) such as retention time, area, tailing factor, and theoretical plates was studied using Box–Behnken design (BBD). Response optimizer was utilized to optimize the experimental conditions. The mobile phase (MP) consisted of ACN and phosphate buffer (0.01 M KH2PO4). The chromatographic separation was performed in C 18 column (250 × 4.6 mm, 5 μm) with ultraviolet (UV) detection set at 225 nm. The method was validated according to the ICH-Q2 (R1) guideline and applied to estimate DAPA and LINA in commercially available fixeddose combination. Results: The study on the effect of the CMPs against the four CQAs using BBD produces second-order polynomial equations. The optimized condition consisted of ACN and phosphate buffer (0.01 M KH2PO4, pH 6.5) in the ratio of 43:57 as a MP maintained at a flow rate of 0.8 mL/min through C 18 column (250 × 4.6 mm, 5 μm) with an oven temperature of 35°C, and UV detection at 225 nm. The method successfully detected the peak of DAPA and LINA at retention times of 4.64 and 7.35 min, respectively, demonstrating good resolution. There was a linear relationship between the concentration of the drugs and their corresponding area, with an R2 value of 0.9975 for DAPA and 0.9996 for LINA over the concentration range of 13.5–24.5 µg/mL and 7.0–13 µg/mL, respectively. The optimized assay conditions were validated according to the ICH-Q2 (R1) guidelines. The method was suitable for the assay of a marketed tablet. The forced degradation study revealed DAPA to be susceptible to alkaline degradation while LINA was prone to acidic, alkaline, oxidative, and photolytic degradation. Conclusion: An analytical method was developed for the quantitative estimation of DAP and LINA using BBD and validated according to the ICH-Q2 (R1) guidelines. The proposed method was utilized for the analysis of drugs in pharmaceutical dosage forms and to assess drug stability under various stress conditions.