Application of QbD based approach in method development of RP-HPLC for simultaneous estimation of antidiabetic drugs in pharmaceutical dosage form

Abstract

The aim of the proposed study was to develop a novel sensitive and rugged stability indicating HPLC method based on an approach of fractional factorial design (FFD) for the simultaneous of estimation of gliclazide and metformin hydrochloride without prior separation in tablets. Preliminary experiments were conducted to identify the critical attribute factors and using Taguchi screening method to assess risk management method process parameters. Later on FFD was applied to optimize the resolution as response between both drugs in short run time. Sixteen experimental runs were performed from grid search data using design of expert software v.7.0. Furthermore, the optimized method was then validated according to the ICH guidelines. The generated model using FFD for the resolution was found to be highly statistically significant (p < 0.05) and after analyzing the optimized zone within the design space, the final chromatographic conditions were selected as mobile phase 60:20:20:0.5, pH 7.5, flow rate 1.0 ml/min and column temperature 25 °C using analytical column C₁₈ Nucleosil ODS (250 × 4.6 mm² i.d, 5 µ) at 227 nm of detector wavelength. Validation of the developed method by QbD has manifested the specificity, accuracy and excellent linearity range and correlation values (R²) 0.997 and 0.996 for drugs. From the analysis it was measured that their LOD and LOQ values for the drugs were 0.035, 0.080 μg/ml and 0.40, 0.55 μg/ml. Therefore, a novel sensitive, accurate and stability indicating method was developed with high degree of practical utility of both drugs estimation in pharmaceutical dosage forms.