Thermodynamics Research Center / ThermoML | Journal of Chemical Thermodynamics

ABSTRACT

Co-solvent plays an important role in drug crystallization. More importantly, the change of temperature and the addition of co-solvent can make the operation of crystallization purification more controllable. In this work, the solubility of diprophylline in methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, water, toluene and mixture of (methanol + water) was experimentally determined at T = 283.15-323.15 K. The solubility data obtained experimentally in all studied pure solvents followed the sequence: water greater than 1,4-dioxane greater than methanol greater than acetonitrile greater than isopropanol greater than ethanol greater than n-propanol greater than ethyl acetate greater than toluene greater than acetone. In addition, in mixture of (methanol + water) the solubility increases at first and then decreases with the increasing mass fraction of methanol. The composition dependence of the solubility has a maximum around (methanol mass fraction) w = 0.4 at all investigated temperatures. Moreover, the effect of solvent properties on solubility is briefly discussed. The modified Apelblat equation, lambdah equation, Jouyban-Acree model and CNIBS/R-K model are applied to correlate the solubility. All the values of RAD and RMSD are no more than 5.34 * 10-2 and 5.83 * 10-4, respectively. Apparent thermodynamic analysis indicates that the dissolution is an endothermic and entropy driven process.