QbD Stressed Development and Validation of Stability-Indicating RP- HPLC Method for the Simultaneous Estimation of Linagliptin and Metformin HCl in Pharmaceutical Dosage Form

Abstract

A new simple stability indicating reverse phase liquid chromatography method was developed by employing Quality by Design (QbD) approach for the simultaneous determination of Linagliptin and Metformin HCl. Within QbD paradigm, the present study aimed to establish the optimization of the RP-HPLC (Reverse phase high performance liquid chromatography) by means of design of experiments and response surface mythology like, Centre composite design (CCD) in order to achieve a good separation and resolution. The developed method is effective to separate Linagliptin and Metformin HCl with a good chromatographic resolution of 6.4. Chromatographic separation was acquired with column Water C18 (250mm x 4.5mm x 5μm) at flow rate 1.0 ml/min with the mobile phase consists of acetonitrile and methanol (75:25 % v/v). The detection of Linagliptin and Metformin HCl was carried out at 245nm. The proposed method was validated according to ICH guidelines. The method was linear in range of 0.5-3μg/ml and 100-600μg/ml of Linagliptin and Metformin HCl respectively and recovery were in the range of 98% to 102%. The degradation product found in stress patterns were well separated among the drug compounds. The method was validated to be specific, rapid, precise and robust for routine analysis in its pharmaceutical dosage form.