Structural, Thermodynamic, and Kinetic Aspects of the Polymorphism and Pseudopolymorphism of Prednisolone (11,17α,21-Trihydroxy-1,4-pregnadien-3,20-dion)

For prednisolone, two polymorphic modifications (forms I and II ) and one sesquihydrate were found. Form I crystallizes in the monoclinic space group P 2 1, whereas form II and the sesquihydrate crystallize orthorhombic in space group P 2 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.