Investigations on the Polymorphism and Pseudopolymorphism of the Glucocorticoid Triamcinolone: New Findings for a Well-Known Drug

Abstract

The glucocorticoid triamcinolone was investigated for polymorphism. If crystalline suspensions of the commercial available drug (form A) are stirred in different solvents, a new and hitherto unknown modification (form B) is always obtained. However, in water, a third form is isolated, which is a monohydrate (form C). Form B represents the thermodynamically most stable solvent-free modification at room temperature, whereas the commercially available form A is metastable. The stable form B crystallizes in the chiral, non-centrosymmetric monoclinic space group P21 with two crystallographically independent molecules in the asymmetric unit. In the crystal structure, the molecules are connected by O−H···O hydrogen bonding into a three-dimensional network. Dehydration of the modification C by thermogravimetry leads to its transformation into the metastable form A. The differential scanning calorimetry (DSC) thermograms of forms B and C exhibit three endothermic events, while form A shows two endothermic events. The last endothermic signal is assigned to the melting of the compounds. The X-ray powder diffraction investigations of the residues formed in these thermal events indicate the formation of at least one additional solvent-free modification.