Equilibrium solubility, Hansen solubility parameter, dissolution thermodynamics, transfer property and preferential solvation of zonisamide in aqueous binary mixtures of ethanol, acetonitrile, isopropanol and N,N-dimethylformamide

The present contribution was devoted to the equilibrium solubility profile, thermodynamics of dissolution process and solvation performance of zonisamide in aqueous binary mixtures of acetonitrile, ethanol, isopropanol and N,N-dimethylformamide (DMF) by using experiment and mathematical correlations. A shake-flask method was used throughout all experimental process under ambient pressure of 101.2 kPa from 278.15 to 323.15 K. The maximum magnitude of equilibrium solubility of zonisamide in neat acetonitrile/ethanol/isopropanol/DMF at T = 323.2 Kwas recorded as 23.28 x 10(-3), 4.460 x 10(-3), 3.522 x 10(-3) and 136.4 x 10(-3) (mole fraction), respectively; while the minimum one was recorded in pure solvent of water (0.01783 x 10(-3) at 278.15 K). The solubility behavior of the drug zonisamide was analyzed through Hansen solubility parameter. The solubility data was represented computationally by various models such as the modified Jouyban-Acree-van't Hoff, Jouyban-Acree, and general single model (GSM), achieving the overall relative average deviations of less than 8.23 %. The relative prominence of interactions of solvent-solvent and solute-solvent molecules upon zonisamide solubility studied through the linear solvation energy relationships indicated that the chief contributions to solubility variation were dipolarity-polarizability and solubility parameter of solutions. The determined solubility data at 298.15 K was analyzed by using the extended Hilde brand solubility approach gaining correlation coefficient of 0.86. According to several solution properties, a quantitative study on preferential solvation was performed by the technique of inverse Kirkwood-Buff integrals. The preferential solvation parameters for neat solvents of isopropanol, acetonitrile, ethanol and DMF were positive in isopropanol/acetonitrile/ethanol/DMF-rich and intermediate proportions in solutions, suggesting that the drug zonisamide was preferentially solvated by the cosolvents (isopropanol/acetonitrile/ethanol/DMF). In these composition regions, it is conjectured that zonisamide is acting as a Lewis acid with the molecules of isopropanol/acetonitrile/ethanol/DMF. Thermodynamic dissolution calculation exhibited an entropy-driven and endothermic dissolution of the drug zonisamide in all the isopropanol/acetonitrile/ethanol/DMF + water mixtures. In addition, the evaluation of enthalpy-entropy compensation specified an enthalpy-drivenmechanism for the solvation of zonisamide. The investigation on transfer properties indicated more advantageous solubilization capability in intermediate proportions of isopropanol/acetonitrile/ethanol/DMF. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the equilibrium solubility profile, dissolution thermodynamics, and solvation behavior of zonisamide in various aqueous binary mixtures. The solubility behavior was analyzed using Hansen solubility parameter and various computational models, with overall deviations less than 8.23%. Solubility variations were mainly influenced by dipolarity-polarizability and solubility parameter of solutions. Thermodynamic dissolution calculations showed an entropy-driven and endothermic dissolution process for zonisamide, with a correlation coefficient of 0.86 using extended Hilde brand solubility approach. Additionally, preferential solvation analysis indicated zonisamide was preferentially solvated by the cosolvents (isopropanol/acetonitrile/ethanol/DMF), with an enthalpy-driven mechanism identified for solvation. These findings suggest more advantageous solubilization capability in intermediate proportions of isopropanol/acetonitrile/ethanol/DMF mixtures.