Thermal analysis of the dehydrated form of a diclofenac salt

Abstract

Thermogravimetric (TG) and differential thermal analysis (DTA) were used to follow the extent of the dehydration of three samples of diclofenac/N-(2- hydroxyethyl) pyrrolidine salt (DHEP) obtained from different batches of the preparation from water at industrial level. The dihydrate salt formed from water, and the anhydrous form obtained from organic solvents, have different crystal structures. The dehydration process carried out at a low temperature is not readily accompanied by the phase transition toward the crystal form of the anhydrous salt. DTA measurements on the dehydrated form of different samples showed an endotherm in the range 73-78°C that represents in all cases the phase transitions from the dehydrated toward the anhydrous form, while the endotherm at a higher temperature (98-111°C) is associated with the melting of the anhydrous form. A small loss of weight on TG profiles (at 68-78°C) was interpreted as a small amount of crystallisation water retained after the dehydration process and released after heating. According to the water amount, thermogram profiles of the examined samples appear modified with respect to the reference compounds. All these aspects suggest that industrial process of the dehydration of a large mass of the dihydrate diclofenac salt cannot be so accurate as the treatment at lab-level, and the small amounts of residual water do not prevent the phase transition.