Solubility Determination and Data Correlation of Paliperidone in Different Pure Solvents at 288.15 to 328.15 K

Abstract

The solubility of paliperidone in 15 pure solvents (methanol, ethanol, i-propanol, n-propanol, n-butanol, n-pentanol, n-hexanol, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, acetone, acetonitrile, tetrahydrofuran, and 1,4-dioxane) was determined using a dynamic laser monitoring method at 0.1 MPa and temperatures ranging from 288.15 to 328.15 K. With increasing temperature, the molar fraction solubility of paliperidone in each solvent also increased. Acetonitrile exhibited the lowest solubility at 288.15 K, whereas 1,4-dioxane showed the highest at 328.15 K. Various models, including the modified Apelblat, Yaws, λh, Wilson, and NRTL models, were applied to correlate and analyze the experimental data. The relative average deviation and root-mean-square deviation indicated strong correlation between experimental and modeled solubility data. Additionally, based on the Wilson model, the thermodynamic analysis of paliperidone dissolution suggested an entropy-driven and spontaneous process, with entropy exerting a greater influence on Gibbs free energy than enthalpy.