Université de Rouen Unité de Croissance Cristalline et de Modélisation Moléculaire (UC2M2), Sciences et Méthodes Séparatives (SMS) UPRES EA 3233, IRCOF rue Tesnière F-76821 Mont Saint-Aignan Cedex France
A combined analysis of structural data and experimental results (DSC, temperature-resolved XRPD and hot stage optical microscopy)
revealed that the dehydration mechanism of cortisone acetate monohydrate (CTA·H2O) involves a collective and anisotropic departure of water molecules followed by a cooperative structural reorganization
toward the anhydrous polymorph CTA (form 2). In spite of the lack of crystal structure data, it can be postulated from experimental
data that thermal decomposition of the dihydrated form (CTA·2H2O) and of the tetrahydrofuran solvate (CTA·THF) toward another polymorph (CTA (form 3)) also proceeds according to a cooperative
mechanism, thus giving rise to probable structural filiations between these crystalline forms of CTA. The crystal structure
determination of two original solvates (CTA·DMF and CTA·DMSO) indicates that these phases are isomorphous to the previously
reported acetone solvate. However, their desolvation behaviour does not involve a cooperative mechanism, as could be expected
from structural data only. Instead, the decomposition mechanism of CTA·DMF and CTA·DMSO starts with the formation of a solvent-proof
superficial layer, followed by the partial dissolution of the enclosed inner part of crystals.
Hot stage optical microscopy observations and DSC measurements showed that dissolved materials (resulting from a peritectic
decomposition) is suddenly evacuated through macroscopic cracks about 30°C above the ebullition point of each solvent. From
this unusual behaviour, the necessity to investigate rigorously the various aspects (thermodynamics, kinetics, crystal structures
and physical factors) of solvate decompositions is highlighted, including factors related to the particular preparation route
of each sample.