Mechanisms for Dehydration of Three Sodium Naproxen Hydrates

Sodium naproxen, a member of the class of nonsteroidal anti-inflammatory drugs (NSAID), exists in an anhydrous form and the following four hydrated ones: one monohydrate, two dehydrates, and one tetrahydrate. In the present work, the authors observed the isothermal dehydration of some of these hydrates by thermogravimetry at several temperatures. The rate of water removal from the crystal was used to determine the mechanism of dehydration in the solid state, by fitting results with selected expressions corresponding to the most common solid-state processes. The water loss was then evaluated according to Eyring's equation, and both changes in activation enthalpy (Delta H*) and activation entropy (Delta S*) were estimated from rate constant values. Experiments made it possible to distinguish different dehydration mechanisms for these hydrate forms, and in particular, to discern the dehydration behavior of two different dihydrate forms, one obtained by crystallizing sodium naproxen from water (CSN) and the other obtained after exposure to 55% RH (DSN). These results add new evidence supporting the X-ray powder diffraction study carried out in this work, showing different patterns for these two forms. X-ray powder diffractometry evaluation of the phase transitions occurring during dehydration of these two dihydrate forms showed that they vary according to dehydration temperature.