Desolvation Kinetics of Sulfameter Solvates

Solvates are often encountered in pharmaceutical solids and knowledge of their physical stability is necessary for their effective formulation. This work investigates the solid-state stability of five structurally related solvates of sulfameter (5-methoxysulfadiazine) by studying the kinetics of their desolvation reaction with thermogravimetric analysis, both isothermally and nonisothermally. Desolvation kinetic analysis was done isothermally by conventional model-fitting and nonisothermally by the complementary method. Calculated kinetic parameters (model, A and Ea) were compared and related to the crystal structure of these solvates. A relationship was established between desolvation activation energy from isothermal results and solvent size; the larger the solvent molecule, the higher its solvate's desolvation activation energy. The best fitting solid-state reaction model correlated to single crystal structural features of sulfameter-solvates where solvent molecules occupied cavities in the unit cell. Finally, it was found that kinetic parameters obtained isothermally and nonisothermally were at variance. Therefore, kinetic results obtained from one method may not be extended to results form the other.