For prednisolone, two polymorphic modifications (forms I and II) and one sesquihydrate were found. Form I crystallizes in the monoclinic space group P2 1 , whereas form II and the sesquihydrate crystallize orthorhombic in space group P2 1 2 1 2 1 . In all forms, the molecules are connected via O-H • • • O hydrogen bonding. Solvent-mediated conversion experiments reveal that form II represents the thermodynamically stable form at room temperature, whereas form I is metastable. This observation could also be independently confirmed by force field calculations. Differential scanning calorimetry (DSC) measurements indicate no polymorphic transformation of one form into the other. The DSC melting point of form I is significantly higher than that of form II, indicating that form I represents the thermodynamically most stable form at higher temperatures and that both modifications behave enantiotropic. This was proven by solvent-mediated crystallization experiments that show that above 130°form II transforms into form I. Dehydration of the sesquihydrate results in the formation of modification I. The 13 C MAS spectra allow distinguishing between all three phases and confirms the crystallographic symmetry. By combining the NMR data with quantum chemical shift calculations on DFT niveau, packing effects were probed.

No abstract

No 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 P2 1 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.