Low-Frequency Raman Spectroscopy of Pure and Cocrystallized Mycophenolic Acid

The aqueous solubility of solid-state pharmaceuticals can often be enhanced by cocrystallization with a coformer to create a binary cocrystal with preferred physical properties. Greater understanding of the internal and external forces that dictate molecular structure and intermolecular packing arra...

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Bibliographic Details
Published in:Pharmaceutics 2023-07, Vol.15 (7), p.1924
Main Authors: Wallace, Catherine S, Davis, Margaret P, Korter, Timothy M
Format: Article
Language:English
Subjects:
Comparative analysis
crystal engineering
Crystal lattices
Crystal structure
Density functionals
Energy
Keywords
Laboratories
Lasers
NMR
Nuclear magnetic resonance
periodic boundary conditions
Pharmaceuticals
Physical properties
Radiation
Raman spectroscopy
Simulation
terahertz vibrations
Thermodynamics
vibrational spectroscopy
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Summary:The aqueous solubility of solid-state pharmaceuticals can often be enhanced by cocrystallization with a coformer to create a binary cocrystal with preferred physical properties. Greater understanding of the internal and external forces that dictate molecular structure and intermolecular packing arrangements enables more efficient design of new cocrystals. Low-frequency (sub-200 cm ) Raman spectroscopy experiments and solid-state density functional theory simulations have been utilized together to investigate the crystal lattice vibrations of mycophenolic acid, an immunosuppressive drug, in its pure form and as a cocrystal with 2,2'-dipyridylamine. The lattice vibrations primarily consist of large-amplitude translations and rotations of the crystal components, thereby providing insights into the critical intermolecular forces governing cohesion of the molecular solids. The simulations reveal that despite mycophenolic acid having a significantly unfavorable conformation in the cocrystal as compared to the pure solid, the cocrystal exhibits greater thermodynamic stability over a wide temperature range. The energetic penalty due to the conformational strain is more than compensated for by the strong intermolecular forces between the drug and 2,2'-dipyridylamine. Quantifying the balance of internal and external energy factors in cocrystal formation indicates a path forward in the development of future mycophenolic acid cocrystals.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15071924