RESUMO
Hydrocortisone was investigated for polymorphism and pseudopolymorphism and three different polymorphic modifications (I-III) and one 2-propanol solvate were found. Forms I and III crystallize in the orthorhombic space group P2(1)2(1)2(1), whereas form II and the 2-propanol solvate crystallize monoclinic in space group P2(1). In all the modifications the molecules are connected by intermolecular O--H...O hydrogen bonding. In the 2-propanol solvate, channels are formed in which the solvent molecules are embedded. Solvent-mediated conversion experiments reveal that the commercially available form I represents the thermodynamically most stable modification at room temperature, whereas forms II and III are metastable. On heating, form III transforms into form II in an endothermic reaction, which shows that an enantiotropic relationship exists between these forms. Form I exhibits the highest melting point and the highest heat of fusion and thus represents the thermodynamically most stable form over the whole temperature range. DSC measurements indicate that form I behaves monotropic to forms II and III. Desolvation of the 2-propanol solvate at higher temperatures results in a transformation into form II, whereas the removal of 2-propanol at room temperature and in vacuum reduced pressure leads to the formation of form III.
Assuntos
Hidrocortisona/química , Termodinâmica , Varredura Diferencial de Calorimetria , Ligação de Hidrogênio , Estrutura MolecularRESUMO
The glucocorticoide triamcinolone diacetate was investigated for polymorphism. Crystallization experiments in different solvents performed at room-temperature reveal that in most cases solvates has formed (form B) which are isotypic and which crystallize in the orthorhombic space group P2(1)2(1)2(1). In their crystal structure channels are formed in which the solvent molecules are located. In some other solvents the commercial available form A is the thermodynamic most stable form. On heating form A using differential scanning calorimetry (DSC) the compound melts at a peak temperature of 136 degrees C without any further polymorphic transformation. If the solvents are removed at higher temperatures using simultaneous differential thermoanalysis and thermogravimetry coupled to mass spectroscopy (DTA-TG-MS) the remaining residues are amorphous against X-rays because the compound melts directly after desolvation. If the desolvation process is investigated by DSC measurements the same is observed for most solvents but in some cases different peaks for desolvation and melting are observed. In this case a new modification can be isolated after removing the solvent (form C). If the solvent are removed in vacuum or by storage at room-temperature always the commercial available form A is obtained, whereas desolvation experiments at 80 degrees C indicate the formation of a further polymorphic modification (form D).