HSPiP and quality by design-assisted optimized analytical method validation for linagliptin and dapagliflozin using HPTLC

Abstract A simultaneous estimation of linagliptin and dapagliflozin from a combination product is still challenging in terms of sensitivity, analytical cost, efficiency, time, simplicity, accuracy, and reproducibility. To circumvent the current issues, a simple, sensitive, efficient, and environmentally sustainable High-Performance Thin-layer Chromatography (HPTLC) method was recommended by employing HSPiP and QbD (quality by design)-enabled optimized strategic approach. HSPiP programme predicted n-hexane, toluene, ethyl acetate, methanol, and aqueous solution of formic acid (0.1%) (ratio of 40:10:5:40:5, v/v) as promising mobile phase for aluminium-backed silica gel 60 F254 plates. Box–Behnken design model identified the critical materials and process parameters. Risk assessment guided the selection of three key parameters (band length, saturation time, and wavelength) to evaluate responses. The developed method resulted in well-resolved bands at R f = 0.41 for linagliptin and R f = 0.66 for dapagliflozin. A linear regression analysis demonstrated high correlation coefficients ( r 2 = 0.9989 for linagliptin and r 2 = 0.9505 for dapagliflozin), meeting the validation criteria outlined by the International Conference on Harmonization (ICH) for accuracy, precision, robustness, limit of detection, and limit of quantification. The validated method was environmentally sustainable as evidenced with high score of AGREEprep and AGREE tools. Conclusively, the method is simple, economic, sensitive, reproducible, and environmentally sustainable for simultaneous estimation of linagliptin and dapagliflozin from fixed combination. Graphical abstract