The solubility and dissolution thermodynamic properties of chloroquine diphosphate in different organic solvents

Abstract

Due to the currently commercial process for production of chloroquine diphosphate with certain disadvantages, there is need to select relevant solvents and to design an optimized production process. The dissolution process of chloroquine diphosphate (form II) in different solvents within the temperature range from 273.15 K to 313.15 K is studied by using the isothermal equilibrium method. Most information in pure solvents is in DMF (3.781 × 10−5 in mole fraction) at 313.15 K, followed by ethanol (2.426 × 10−5), n-propanol (1.153 × 10−5) and isopropanol (8.20 × 10−6). In mixtures of isopropanol (1-w) + DMF (w), the solubility values increase monotonically with the increasing mass fraction (w) of DMF. However, in the system of ethanol (1-w) + DMF (w), solubility increases first, and then decreases with the composition as DMF increases. The maximum value is (4.466 × 10−5) at w = 0.40 at 313.15 K, an increase about 2 fold. The solubility process depends on the chemical properties of solvent such as the hydrogen bond acidity (α), hydrogen bond basicity (β), dipolarity/polarizability (π*) and the Hildebrand solubility parameter (δ2 H), which are discussed. Moreover, the solubility results are evaluated by the modified Apelblat equation and Jouyban-Acree model, and the values of relative average deviation (RAD) are all less than 1.11% in pure organic solvents, and no more than 4.03% in two mixtures. Besides, the calculation of apparent thermodynamic analysis indicates that the dissolution is an endothermic, spontaneous and entropy driven process.