Nisoldipine in Several Aqueous and Non-Aqueous Cosolvent Solutions: Solubility Modeling and Preferential Solvation Research

Abstract

The study mainly reported the equilibrated solubilities of nisoldipine in aqueous solutions of n-propanol/acetonitrile + water and non-aqueous solutions of ethyl acetate + ethanol/isopropanol by dint of experimentation and model correlations. Solubility was experimented via the shake-flask method under 101.2 kPa from 278.15 to 318.15 K. The maximum of nisoldipine solubility (in mole fraction unit) was found in neat n-propanol/acetonitrile/ethyl acetate at 318.15 K, and the minimum was found in neat water/isopropanol/ethanol. The total and three-dimensional Hansen solubility parameters were employed herein to explain the solubility behavior of nisoldipine. Modeling solubility through mixture response surface, Jouyban−Acree, and Jouyban−Acree−van't Hoff models resulted in relative average deviations of <10.3%. Quantitative research upon preferential solvation was carried out by applying the approach of inverse Kirkwood−Buff integrals for the four solution systems considered in the present study and two aqueous solutions of ethanol/isopropanol reported in the literature. The local fractions of n-propanol/ acetonitrile/ethanol/isopropanol for the four aqueous solutions as well as ethyl acetate for non-aqueous solution of ethyl acetate + isopropanol were greater than that of bulk ones in n-propanol/acetonitrile/ethanol/isopropanol/ethyl acetate-rich and middle composition proportions, demonstrating that the solvation of nisoldipine was preferred by cosolvents (n-propanol/acetonitrile/ ethanol/isopropanol/ethyl acetate). It is able to speculate that nisoldipine displays Lewis acid behavior in these regions with the cosolvent molecules in aqueous solution systems and with the ethyl acetate molecules or isopropanol in the ethyl acetate + isopropanol solution system.