Molecular-Level Interactions of Dapagliflozin Propanediol Monohydrate Antidiabetic Drug with d‑(+)-Glucose in Aqueous...

In this work, volumetric, acoustic, viscometric, photon correlation, and near-infrared spectroscopic studies on an antidiabetic drug, dapagliflozin propanediol monohydrate (DPM) have been reported in binary mixtures in aqueous media and ternary systems with d-(+)-glucose. Volumetric studies show a structure-breaking nature of DPM at low (approximately from 0.5 × 10^-4 mol kg^-1 to 1.5 × 10^-4 mol kg^-1) and high (approximately from 2.5 × 10^-4 mol kg^-1 to 3.5 × 10^-4 mol kg^-1) concentrations, whereas a structure-making nature is observed at intermediate (approximately from 1.5 × 10^-4 mol kg^-1 to 2.5 × 10^-4 mol kg^-1) concentrations. Acoustic study suggests that the formation of water structure around DPM is the most prominent at intermediate concentrations. Absorption spectra in the range of 5800-4600 cm^-1 show a shift in absorption maxima to the left at low concentrations and to the right at high concentrations. DPM exhibits a breaking-making-breaking behavior of the water structure with increasing concentration in aqueous media. DPM-DPM interactions predominate over DPM-water interactions at lower and higher limiting temperatures, and the opposite occurs at intermediate temperatures. In the low-temperature range, the absorption maxima shift dramatically to a higher frequency region with increasing temperature, but in the high-temperature range, no major shift is observed, and an isosbestic point is noted. A breaking-making-breaking nature of the water structure is observed with increasing concentration of d-(+)-glucose in DPM-d-(+)-glucose-water systems. A small amount of d-(+)-glucose (up to 10 × 10^-3 mol kg^-1) causes water structure breaking by pulling out water from the hydration layers of DPM, and further addition helps to add water molecules around DPM. With increasing temperature (from 293.15 to 333.15 K), a making-breaking-making nature of the water structure is observed. Finally, molecular-level interactions of DPM and d-(+)-glucose in an aqueous environment under perturbations of concentration and temperature have been established.