Solubility Determination, Model Correlation, and Solvent Effect Analysis of Nisoldipine in Different Solvent Systems at a Series of Temperature

Abstract

In this work, the solubility of nisoldipine in ethyl acetate, toluene, 1-butanol, 1-propanol, ethanol, acetonitrile, water, 2-propanol, cyclohexane, and two binary solvents mixtures (2-propanol/ethanol + water) at the temperature ranging from 278.15 to 318.15 K, solvent effect in a monosolvent system, and model correlation are studied. The solubility of nisoldipine is positively correlated with temperature. At a certain temperature, the subsequence of solubility of nisoldipine was of the order ethyl acetate (2.782 × 10–2, 298.15 K) > acetonitrile (1.687 × 10–2, 298.15 K) > 1-butanol (1.105 × 10–2, 298.15 K) > 2-propanol (9.350 × 10–3, 298.15 K) > 1-propanol (7.804 × 10–3, 298.15 K) > ethanol (6.483 × 10–3, 298.15 K) > toluene (3.092 × 10–3, 298.15 K) > cyclohexane (1.114 × 10–4, 298.15 K) > water (1.154 × 10–5, 298.15 K). To study the effect of solvation interaction on solubility, the solute–solvent and solvent–solvent interactions were studied. Hydrogen-bonding acceptor (HBA) interaction of the solvent with the solute and nonspecific dipolarity/polarizability interactions are in favor of the increase of solubility of nisoldipine. In addition, the solubility increases with an increasing composition of 2-propanol or ethanol and decreases with an increase of water. Four thermodynamic models (modified Apelblat model, λh model, Jouyban–Acree model, and Apelblat–Jouyban–Acree model) were used to correlate the relationships between the solubility of nisoldipine and temperature. The correlation results obtained from all systems show that the largest values of relative average deviation (RAD) and root-mean-square deviation (RMSD) are 1.35% and 1.13 × 10–4, respectively. Moreover, statistical analysis was used to evaluate the appropriateness of the models; in a word, these four models can describe the solubility behavior of nisoldipine very well.