Abstract-Terahertz Spectroscopy and Computational Investigation of the Flufenamic Acid/Nicotinamide Cocrystal

Sean Delaney and Timothy Michael Korter

J. Phys. Chem. A, Just Accepted Manuscript

DOI: 10.1021/jp5125519

Publication Date (Web): March 18, 2015

Copyright © 2015 American Chemical Society

http://pubs.acs.org/doi/abs/10.1021/jp5125519

Terahertz spectroscopy probes the low-frequency vibrations that are sensitive to both the intermolecular and intramolecular interactions of molecules in the solid-state. Thus, terahertz spectroscopy can be a useful tool in the investigation of crystalline pharmaceutical compounds, where slight changes in the packing arrangement can modify the overall effectiveness of a drug formulation. This is especially true for cases of polymorphic systems, hydrates/solvates, and cocrystals. In this work, the cocrystal of flufenamic acid with nicotinamide was investigated using terahertz spectroscopy and solid-state density functional theory. The solid-state simulations enable understanding of the low-frequency vibrations seen in the terahertz spectra, while also providing insight into the energetics involved in the formation of the cocrystal. The comparison of the cocrystal to the pure forms of the molecular components reveals that the cocrystal has better overall binding energy, driven by increased intermolecular hydrogen bond strength and greater London dispersion forces, and that the trifluoromethyl torsional potential is significantly different between the studied solids.