Investigation on co-solvency, solvent effect, Hansen solubility parameter and preferential solvation of fenbufen dissolution and models correlation

Abstract

The solubility behavior as a significant molecular property in pharmaceuticals development is challenging in modern pharmaceutical industry. The high quality solubility is advantageous to crystal forms optimization, dosage forms design and product purification. In this work, the saturated solubility of fenbufen in 2-butanone, acetone, ethyl acetate, 1-propanol, 2-propanol, 1-butanol, methanol, ethanol, acetonitrile, water, cyclohexane, toluene and two mixtures (ethanol + water and acetone + water) at region of 278.15 K-318.15 K was measured by employing isothermal saturation method. The preferential solvation investigation, solvent effect analysis, Hansen solubility parameters discussion, models correlation and thermodynamics properties were explored. The molarity solubility of fenbufen present as a positive relation with temperature and enhance as the rise of temperature with a different rate of increase in different solvents. In view of mono-solvent systems, the tendency of molarity solubility was as 2-butanone > acetone > ethyl acetate > 1-butanol > 1-propanol > ethanol > methanol > 2-propanol > acetonitrile > toluene > water > cyclohexane. Solvent effect was analyzed by KAT-LSER model which indicated that the solute–solvent interactions came into prominence in solubility of fenbufen. In addition, the Hansen solubility parameter (HSP) was employed to discuss the dissolution ability of solvents to fenbufen. In view of mixtures systems, the co-solvency phenomenon appeared in acetone + water systems. The solubility of fenbufen in mixtures could be explained in depth by HSP. Moreover, the preferential solvation of fenbufen was investigated by IKBI method. The positive preferential solvation parameters (δx1,3) occurred at 0.24 < x1 < 1 for ethanol (1) + water (2) mixtures and 0.20 < x1 < 0.70 for acetone (1) + water (2) which indicated that ethanol/acetone solvated fenbufen preferentially. In other regions, the δx1,3 values were negative which indicated that water solvated fenbufen preferentially. What’s more, fenbufen solubility data was correlated by four famous models (Apelblat, Wilson, Jouyban-Acree and Apelblat-Jouyban-Acree models). The maximum relative average deviation (RAD) and root-mean-square deviation (RMSD) values were 1.99% and 3.35 × 10-4 for mono-solvents systems, 1.91% and 1.30 × 10-4 for mixtures systems, respectively. Finally, all positive values of these thermodynamics properties illustrated that the dissolution of fenbufen was an entropy increment and endothermic process.