Measurement and mathematical correlation of the solubility of urea in polar protic solvents

The accurate determination of the solubility of an active pharmaceutical ingredient in a solvent is essential for the design and development of the purification process. The solubility of urea in nine polar protic solvents (water, methanol, ethanol, 1-propanol, isopropanol, 1-butanol, isobutanol, 1-pentanol and isopentanol) was measured by dried gravimetric method from 20-70 degrees C (293.15-343.15 K). The solubility of urea in selected solvents was found to increases with temperature. The solubility of urea was highest in water and lowest in pentanol. The mole fraction (x) solubility of urea was correlated with the modified Apelblat equation and lambda h equation. The maximum relative average radiation (RAD) and root-mean-square deviation (RMSD) predicted were 0.0021 (Apelblat) and 0.0011 (lambda h), respectively. The maximum values of RMSD were 3.57 x 10- 8 (Apelblat) and 0.6160 x 10- 8 (lambda h), respectively. The lambda h equation showed a better fit with experimental values for the solubility of urea. The RAD and RMSD values were smaller in all selected solvents, ranging from -0.0006 to 0.0011 and 0.0003 x 10- 8 to 0.6160 x 10-8, respectively. The thermodynamic energy properties of the solution were calculated using the van 't Hoff equation. The obtained values of Delta H, Delta S and Delta G were found to be positive, indicating that the dissolution process was an endothermic, entropy-driven and non-spontaneous process. Water exhibited the most favourable thermodynamics for urea dissolution, likely due to stronger interactions arising from its higher polarity and linear structure compared to the alcoholic solvents. The solubility data, solubility model and thermodynamic parameters of urea are of great significance to the application of industrial urea production and crystallisation.