Mechanisms for Dehydration of Three Sodium Naproxen Hydrates

Abstract

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

Evaluation of Sodium Naproxen Hydrated Forms by Isoconversional Analysis

“…A dehydration occurring by one-step mechanism has been revealed for the MSN and DSN, while a multi-step mechanism explains the dehydration of CSN and TSN. The results of this study showed a good correlation with those previously determined by applying an isothermal method [1]. In conclusion, the isoconversional analysis may be considered as a simple and fast method to predict the conversional behaviour of pharmaceutical substances and it may be applied to predict the phase transition of complex systems.…”

“…Mechanisms of dehydration have been previously determined by an isothermal method [1,2]. In this study, their dehydration was followed by an isoconvertional analysis (ICA), which is based on a nonisothermal method.…”

Simultaneous UV Imaging and Raman Spectroscopy for the Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

“…). Various hydrate forms of sodium naproxen with complex structure (at least monohydrate, dihydrate, and tetrahydrate, as well polymorphic hydrate forms) have been reported in the literature . However, detailed assignment of the molar ratio of water of crystallization for these intermediate species detected was not possible from the Raman spectra.…”

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

“…The physical stability of hydrates and anhydrous forms strongly depends upon the relative humidity and/or temperature of the environment [46][47][48], and transitions from one form to the other occur as a consequence of variations in storage conditions and/or technological treatments [37,49].…”