Analytical Quality by Design (aqbd)-based Development and Validation of a Robust Rp-hplc Method for the Quantitative Estimation of Empagliflozin in Pharmaceutical Dosage Forms
Year: 2026
Type: article
Abstract: Background: Empagliflozin, a selective sodium-glucose co-transporter-2 (SGLT2) inhibitor, is widely prescribed for the management of type 2 diabetes mellitus and has demonstrated significant cardiovascular and renal protective effects. Owing to its extensive clinical use, a robust, reliable, and stability-indicating analytical method is essential for routine quality control. Analytical Quality by Design (AQbD) has emerged as a systematic approach that integrates risk assessment, Design of Experiments (DoE), and lifecycle management to develop analytical procedures with enhanced robustness and regulatory flexibility. (Objective: The present study aimed to develop and validate a robust AQbD-based reverse-phase high-performance liquid chromatographic (RP-HPLC) method for the quantitative estimation of empagliflozin in bulk drug and pharmaceutical dosage forms.Methods: The Analytical Target Profile (ATP) was established before method development. Critical Method Parameters (CMPs), including mobile phase composition, flow rate, column temperature, and detection wavelength, were identified through preliminary risk assessment using Ishikawa diagrams and Failure Mode and Effects Analysis (FMEA). A Design of Experiments approach employing response surface methodology was used to optimize chromatographic conditions. Method validation was performed according to ICH Q2(R2) recommendations by evaluating specificity, linearity, accuracy, precision, robustness, detection limit, quantification limit, and system suitability. Results: The optimized chromatographic method demonstrated excellent peak symmetry, acceptable retention time, and satisfactory resolution. Calibration exhibited excellent linearity across the selected concentration range with correlation coefficient greater than 0.999. Accuracy and precision complied with ICH acceptance criteria, while robustness studies confirmed that small deliberate variations in analytical parameters did not significantly influence method performance. The AQbD strategy enabled establishment of a Method Operable Design Region (MODR), ensuring reliable analytical performance during routine analysis. Conclusion: The proposed AQbD-assisted RP-HPLC method is accurate, precise, robust, economical, and suitable for routine quality control of empagliflozin in pharmaceutical dosage forms. Integration of AQbD principles significantly improved method understanding, robustness, and lifecycle management compared with conventional trial-and-error analytical development approaches.
Institution: Shri Venkateshwara University
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W7204273577