Greenness assessment and stability-indicating HPTLC method for the concurrent analysis of empagliflozin and metoprolol succinate in a novel combined oral formulation.

BACKGROUND

Empagliflozin a sodium-glucose co-transporter 2 inhibitor, and Metoprolol succinate, a cardioselective β1-blocker, are co-formulated in a novel bilayer tablet currently under clinical evaluation. Reliable stability-indicating methods are required for simultaneous quantification of these drugs and to ensure environmental sustainability of pharmaceutical analysis.

OBJECTIVE

To develop and validate a stability-indicating HPTLC method for concurrent quantification of EMP and METO in a novel combined oral formulation, in compliance with ICH Q2(R2) guidelines.

METHODS

Chromatographic separation was achieved on HPTLC silica gel 60 F254 plates using chloroform: methanol: toluene (3.0:2.5:4.5, v/v/v) as mobile phase. Detection was carried out at 222 nm. The method was validated for specificity, linearity, accuracy, precision, robustness, and sensitivity. Stressed degradation studies under acid, base, oxidative, thermal, and photolytic conditions were performed.

RESULTS

EMP and METO exhibited Rf values of 0.54 and 0.26, respectively. Linearity was observed over 100-600 ng/band for EMP (r2 = 0.9987) and 500-3000 ng/band for METO (r2 = 0.9998). Recovery ranged from 99.54-101.21% (EMP) and 98.23-100.73% (METO). LOD/LOQ values were 24.67/74.76 ng/band (EMP) and 45.29/137.25 ng/band (METO). The method demonstrated precision in both intraday (EMP-8738.68 ± 80.86 and METO- 4510.93 ± 27.61) and interday (EMP-8744.97 ± 131.91 and MET0-4492.87 ± 32.53) analyses and repeatability, with the %RSD of the peak area remaining below 2%. The stressed degradation conditions were optimized to induce degradation ranging from 5% to 20%.

CONCLUSION

The validated HPTLC method is precise, accurate, and stability-indicating, making it suitable for routine quality control and stability testing of EMP-METO bilayer tablets.