Glyburide in a series co-solvent solutions: Solubility and modeling, solvation and quantum chemistry research

Abstract

The shake-flask technique was used to test the solubility of glyburide in mixtures of acetone + water and ethyl acetate + methanol/ethanol/isopropanol under 101.0 kPa. For a fixed temperature, the glyburide solubility positively increased with the mass fraction of acetone in the acetone + water mixture, and reached a maximum value of 8.805 × 10−6 at 298.15 K. The solubility magnitudes reach their peak when the mass fraction of ethyl acetate in solutions containing ethyl acetate plus methanol/ethanol/isopropanol is approximately 0.3, which correspond to 5.703 × 10−4, 5.235 × 10−4 and 4.307 × 10−4, respectively, at 298.15 K. Two models-the Jouyban-Acree and modified van't Hoff-Jouyban-Acree were employed to correlate the solutility and produced the biggest relative average deviation of 7.78 %. The local composition (solvents) around the drug molecule was investigated at 298.15 K using an inverse Kirkwood-Buff integrals. The positive preferred solvation parameters of glyburide were observed in the medium and rich compositions of methanol/n-propanol/isopropanol/acetonitrile/PG/NMP (taken from published works)/acetone, signifying that glyburide was preferentially solvated by these solvents; while they had negative magnitudes in ethyl acetate + methanol/ethanol/isopropanol systems throughout the whole ethyl acetate compositions. The solubility of glyburide in the ten solutions was properly described by an extended Hildebrand solubility parameter approach, with relative average errors of no more than 5.32 %. In addition, the electrostatic characteristics of the basicity/acidity of glyburide molecule were highlighted with the help of quantitative study of molecular surface. Because of their lowest (-158.0 kJˑmol−1 to −136.6 kJˑmol−1) and largest (156.6 kJˑmol−1 to 182.8 kJˑmol−1) global electrostatic potentials, the > C = O and > NH groups are the main targets of electrophilic and nucleophilic assault. Visual examination of the weak interactions between glyburide and the neat solvents (methanol, ethanol, isopropanol, acetone, ethyl acetate, and water) was done using the Hirshfeld partition analysis-based independent gradient model.