Abstract
A simple, sensitive, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of saxagliptin (SAXA) and dapagliflozin (DAPA) in pharmaceutical formulation. Design of experiments (DoE) was applied for multivariate optimization of the experimental conditions of RP-HPLC method. Risk assessment was performed to identify the critical method parameters. Three independent factors; mobile phase composition, flow rate and column temperature were used to design mathematical models. Central composite design (CCD) was used to study the response surface methodology and to study in depth the effects of these independent factors. Desirability function was used to simultaneously optimize the retention time and resolution of SAXA and DAPA. The optimized and predicted data from contour diagram consisted of acetonitrile and ortho phosphoric acid (0.1%) in the ratio of 50:50 respectively, at a flow rate of 0.98 ml/min and column temperature 31.4 °C. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 6 min were achieved. The optimized assay conditions were validated according to ICH guidelines. Hence, the results clearly showed that Quality by design approach could be successfully applied to optimize RP-HPLC method for simultaneous estimation of SAXA and DAPA.
Highlights
Saxagliptin (SAXA), chemically, known as (1s,3s,5s)-2-[(2s)-2-amino-2-(3-hydroxyltricyclo[3.3.1.1]dec-1-yl)acetyl]-2-azabicyclo[3.1.0] hexane-3-carbonitrile (Figure 1), is a potent, selective, long-acting, and reversible inhibitor of the enzyme dipeptidyl peptidase 4 (DPP-4) used for treatment of type 2 diabetes mellitus
Dapagliflozin (DAPA) is chemically described as (1s)-1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxy phenyl) methyl]phenyl]-D-glucitol (Figure 2) (Meira et al, 2017). It belongs to a new class of oral antidiabetic drugs called sodium glucose cotransporter 2 (SGLT2) inhibitors
Literature has depicted very critical care and typical reports of reverse phase high performance liquid chromatographic (RP HPLC) for simultaneous estimation of SAXA and DAPA in bulk and tablet form namely, a new stability indicating by the RP HPLC method (Vinutha, Chowdary, Prasad, 2017) and precise UPLC (Madhavi, Prameela Rani, 2017)
Summary
Saxagliptin (SAXA), chemically, known as (1s,3s,5s)-2-[(2s)-2-amino-2-(3-hydroxyltricyclo[3.3.1.1]dec-1-yl)acetyl]-2-azabicyclo[3.1.0] hexane-3-carbonitrile (Figure 1), is a potent, selective, long-acting, and reversible inhibitor of the enzyme dipeptidyl peptidase 4 (DPP-4) used for treatment of type 2 diabetes mellitus. An extensive literature survey has revealed that there is no reverse phase high performance liquid chromatographic (RP HPLC) method available for individual or simultaneous estimation of SAXA and DAPA in bulk, or pharmaceutical dosage forms use an experimental design approach. Literature has depicted very critical care and typical reports of RP HPLC for simultaneous estimation of SAXA and DAPA in bulk and tablet form namely, a new stability indicating by the RP HPLC method (Vinutha, Chowdary, Prasad, 2017) and precise UPLC (Madhavi, Prameela Rani, 2017). These methods did not describe the design space as per recent FDA guidelines. Our quest for developing a simple, rapid, precise, robust RP HPLC method for analysis of SAXA and DAPA, assisted with DoE, was developed and central composite design (CCD) for evaluation of robustness of developed method, followed by graphical interpretation of data by response surface methodology (RSM)
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