Investigations on the Desolvation Reaction of Pseudopolymorphic Forms of Hydrocortisone

Suitchmezian, Viktor; Jeß, Inke; Näther, Christian

doi:10.1021/cg8002838

Cited by 15 publications

(7 citation statements)

References 37 publications

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“…In our own investigations, we have discovered a large number of hitherto unknown modifications, and we have studied their stability and transition behavior in detail. – In recent investigations, our interest focused on prednisolone, also known as 1,2-dehydrocorticosterone or as 11,17α,21-trihydroxy-1,4-pregnadien-3,20-dion (Scheme ), which possesses a strong antirheumatic activity and less undesired effects. , …”

Section: Introductionmentioning

confidence: 99%

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

Suitchmezian

Jeß

Sehnert

et al. 2008

Crystal Growth & Design

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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.

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Section: Introductionmentioning

confidence: 99%

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

Suitchmezian

Jeß

Sehnert

et al. 2008

Crystal Growth & Design

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“…113 Crystal structures of the chloroform and N,N -dimethylformamide solvatomorphs of hydrocortisone were reported, and contrasted with the previously reported structures of the isopropanol, methanol, and pyridine solvates. 114 Desolvation of the solvatomorphs yielded either the stable Form-I or metastable Form-II, indicating the existence of desolvation pathways to solvent-free crystal forms of hydrocortisone.…”

Section: Solvatomorphic Systemsmentioning

confidence: 99%

Polymorphism and Solvatomorphism 2009

Brittain¹

2011

Journal of Pharmaceutical Sciences

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“…Some years ago we reported on the polymorphism of some glucocorticoids, still among the most effective and versatile drugs. − In the course of this project we detected several new polymorphic modifications and cocrystals for, e.g., hydrocortisone, triamcinoloneacetonide, and prednisolone. − …”

Section: Introductionmentioning

confidence: 99%

Trimorphism of Betamethasone Valerate: Preparation, Crystal Structures, and Thermodynamic Relations

Näther

Jeß

Seyfarth

et al. 2014

Crystal Growth & Design

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The glucocorticoide bethamethasone valerate was investigated for polymorphism. The commercially available modification (Form I) and one methanol solvate were characterized by single crystal structure analysis. DTA-TG and DSC investigations reveal that on solvent removal the methanol solvate decomposes into a new polymorphic modification (Form III), which, upon further heating, transforms into another modification (Form II) via melting and recrystallization. The crystal structures of forms II and III were determined by a combination of 13 C NMR spectroscopy and X-ray powder diffraction. In all modifications as well as in the methanol solvate differences in the conformation and the packing of the molecules are observed. Solvent mediated conversion experiments reveal that form I represents the thermodynamically stable form at room temperature. Thermomicroscopic, XRPD, and heating rate dependent DSC measurements on forms I−III do not show any interconversion of these forms via the solid. Further DSC measurements indicate both a higher melting point and heat of fusion for form I compared to form II and form III. Therefore, form I should also be the thermodynamically stable form over the whole temperature range and all forms seems to be monotropically related.

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Investigations on the Desolvation Reaction of Pseudopolymorphic Forms of Hydrocortisone

Abstract: Details on the structure determination of hydrocortisone chloroform solvate (4).Details on the structure determination of hydrocortisone N,N'dimethyl formamide solvate (5).

Cited by 15 publications

References 37 publications

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

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

Polymorphism and Solvatomorphism 2009

Trimorphism of Betamethasone Valerate: Preparation, Crystal Structures, and Thermodynamic Relations

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