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Interrelation between thermochemical and structural data of polymorphs exemplified by diflunisal
German L Perlovich1, Lars Kr Hansen, Annette Bauer-Brandl
1University of Tromsø, Institute of Pharmacy, Breivika, N-9037 Tromsø, Norway.
Journal of Pharmaceutical Sciences
|April 12, 2002
Summary
Polymorphic forms of diflunisal (A, B, C, D) were investigated using various analytical methods. Their crystal structures and lattice energies were compared, revealing relationships between molecular properties and crystal packing.
Area of Science:
- Solid-state chemistry
- Materials science
- Crystallography
Background:
- Diflunisal exhibits polymorphism, with multiple known solid-state forms.
- Understanding these polymorphic forms is crucial for drug formulation and stability.
Purpose of the Study:
- To synthesize and characterize new and known unsolvated polymorphic phases of diflunisal.
- To investigate the relationships between molecular structure, crystal packing, and physical properties of diflunisal polymorphs.
Main Methods:
- X-ray diffraction (XRD) for structural analysis.
- Infrared (IR) spectroscopy to study molecular vibrations.
- Solution calorimetry and Differential Scanning Calorimetry (DSC) for thermodynamic characterization.
Main Results:
- Four unsolvated polymorphic phases (A, B, C, D) of diflunisal were studied, including a new phase D.
- Relationships were established between O-H/C=O stretching frequencies and molecular volume.
- Crystal lattice energies showed small differences, indicating "isoenergetic" polymorphs, with order A < B < C < E < D by volume and B ≈ A < C < D by lattice energy.
Conclusions:
- Polymorphism in diflunisal is influenced by molecular conformational flexibility, hydrogen bonding capabilities, and the balance between van der Waals and hydrogen bond interactions.
- Forms A and C are enantiotropic, while B, C, D, and A, B, D are monotropic.
- The study provides insights into the factors governing diflunisal's solid-state behavior.