Green liquid chromatographic method for simultaneous determination of metformin, linagliptin and rivaroxaban: Tablet manufacturing and application to in-vitro dissolution studies

Abstract

Single-pill fixed combination therapy enhances patient adherence and facilitates the effective management of asymptomatic conditions such as cardiovascular disease and diabetes etc. Considering the potential need for a fixed triple-dose combination of metformin HCl, linagliptin and rivaroxaban, here we report, fixed-dose film-coated tablet manufacturing of three co-prescribed drugs (metformin HCl, linagliptin, rivaroxaban) and development of assay method for its analysis followed by in-vitro drug release profile. The analysis was performed under isocratic conditions using phosphate buffer (pH 6.8): ACN (70:30) at 1.00 mL min−1 flow rate. The detector wavelength was adjusted at 248 nm. ICH guidelines were followed for method validation. Linearity was found to be 40–1500, 0.2–7.50 and 0.80–30 µg mL−1 with quantification limits 24.05, 0.264 and 0.565 μg mL−1 for metformin HCl, linagliptin and rivaroxaban respectively. The good reproducibility of the developed method confirmed its suitability for its intended use in routine analyses as per pharmaceutical quality control practices. Greenness evaluation of the proposed method using AES score, AMVI, AGREE, and NEMI tools suggested that the method is environment friendly.