Investigations on the Desolvation Reaction of Pseudopolymorphic Forms of Hydrocortisone
2009-02-04T00:00:00Z (GMT) by
The crystal structures of two pseudopolymorphic modifications of the glucocorticoid hydrocortisone were determined, in addition to the known structures of the 2-propanol (<b>1</b>), methanol (<b>2</b>) and pyridine (<b>3</b>) solvate reported recently. The chloroform solvate (<b>4</b>) and the <i>N</i>,<i>N</i>′-dimethylformamide solvate (<b>5</b>) crystallize in the monoclinic space group <i>P</i>2<sub>1</sub>, with <i>a</i> = 12.5947 (8) Å, <i>b</i> = 12.4413 (5) Å, <i>c</i> = 14.9884 (11) Å, β =90.571 (9)°, <i>V</i> = 2348.5(2) Å<sup>3</sup> for (<b>4</b>) and <i>a</i> = 13.4186 (10) Å, <i>b</i> = 6.0878 (3) Å, <i>c</i> = 14.6595 (11) Å, β = 104.711 (10)°, <i>V</i> = 1158.27(14) Å<sup>3</sup> for <b>5</b>. The crystal structures of <b>1</b>, <b>3</b>, and <b>5</b> are isotypic and are very similar to that of the thermodynamically metastable solvent free modification <b>III</b> of hydrocortisone. The removal of solvents from the pseudopolymorphic forms at elevated temperatures results in the formation of the thermodynamically most stable form <b>I</b> or the metastable form <b>II</b> of hydrocortisone. For the methanol solvate, the desolvation reaction indicates the formation of a new modification of this drug. In contrast, the removal of the solvent from the <i>N</i>,<i>N</i>′-dimethylformamide solvate (<b>5</b>) at room-temperature leads to the formation of the metastable form <b>III</b> of hydrocortisone. These results indicate a smooth reaction pathway for the desolvation reactions of the solvates into the solvent free modifications of hydrocortisone.