Effect of polymorphism on thermodynamic properties of cefamandole nafate

• Effect of polymorphism on thermodynamic properties of cefamandole nafate was investigated.
• The solid–liquid equilibrium of cefamandole nafate form I and form II were experimentally determined and compared.
• Several solution thermodynamic properties of cefamandole nafate were calculated.

For solid state active pharmaceutical ingredient (API), it might be able to exist in different crystal structures, which is well known as polymorphism. Different polymorphs of the same pharmaceutical might exhibit different physicochemical properties. In this work, the effect of polymorphism on thermodynamic properties of cefamandole nafate was investigated in detail. Two new polymorphic forms of cefamandole nafate were successfully prepared and characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). It was found that form IV has higher melting temperature than form V. By using dynamic method, the solid–liquid equilibrium of cefamandole nafate form IV and form V were experimentally determined and compared in (ethanol + water) binary solvent mixtures over the temperature ranges of (278.15–308.15) K. The effects of solvent and temperature on the solubility of these two forms were discussed. It was found that the solubility data of cefamandole nafate form V are higher than those of form IV. The experimental solubility data were correlated by the modified Apelblat equation, the CNIBS/R–K equation and the Jouyban–Acree model, respectively. Furthermore, the dissolution thermodynamic properties, including the enthalpy, entropy and Gibbs free energy change, were also calculated. Combining the results of DSC analysis, the solubility and the thermodynamic properties, it can be concluded that the thermodynamic properties of the two forms are apparently different.