Central Composite Design-assisted development and validation of HPTLC method for simultaneous determination of azelnidipine and metoprolol succinate

Azelnidipine and Metoprolol Succinate are commonly used together for hypertension. A simple, reliable method is required for simultaneous determination in formulations. Objective: This study aimed to develop, optimize, and validate a HPTLC method for simultaneous estimation of both drugs using an analytical quality by design (AQbD) approach. The method was developed on silica gel 60 F254 plates with Toluene acetate (6:3:0.2:0.2, v/v/v/v) as the mobile phase, with densitometric detection at 227 nm. Toluene, methanol, and chamber saturation time were optimized using a 17-run central composite design. The method was validated according to ICH Q2(R2) guidelines. Environmental impact, performance, practicality, and sustainability were assessed using AGREE, GAPI, RAPI, BAGI, and WECA tools. The optimized method provided resolved bands for both drugs with Rf values of 0.48 ± 0.01 and 0.28 ± 0.01, respectively, with resolution of 2.15 ± 0.04. Linearity was obtained over 1600–8000 ng/band and 2500–12500 ng/band, with correlation coefficients of 0.9988. Precision, accuracy, specificity, and robustness were satisfactory. AGREE, GAPI, RAPI, BAGI, and WECA scores were 0.53, 62%, 70, 72.5%, and 83%, respectively. The HPTLC method is simple, accurate, precise, robust, practical, and sustainable.