Conformational origins of polymorphism in two forms of flufenamic acid

Delaney, Sean P.; Smith, Tiffany; Korter, Timothy M.

doi:10.1016/j.molstruc.2014.02.001

Cited by 27 publications

(39 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 In all cases, the predicted vibrations match well with the observed spectral features arising from the −CF 3 motions. Given the excellent correlation between theory and experiment, the −CF 3 torsions in these solids must be quasi-harmonic, indicating that the vibration is oscillating near the bottom of its potential well, far from the top of the barrier.…”

Section: Relative Energies Of the Molecular Solidssupporting

confidence: 66%

See 1 more Smart Citation

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

Delaney

Korter

2015

J. Phys. Chem. A

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Relative Energies Of the Molecular Solidssupporting

confidence: 66%

“…Further details on the optimized structures of the pure FFA can be found elsewhere. 27 3.2.2. Vibrational Analyses.…”

Section: Methodsmentioning

confidence: 99%

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

Delaney

Korter

2015

J. Phys. Chem. A

Self Cite

View full text Add to dashboard Cite

show abstract

“…32 In the FFA-NIC CO structure, hydrogen-bonded rings are formed by two FFA and two NIC molecules. These four-molecule rings are linked into infinite tubes by the amide chain motif.…”

Section: Ffa I and Ffa Cocrystals Characterization Morphology Predicmentioning

confidence: 99%

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

et al. 2017

View full text Add to dashboard Cite

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinyl pyrrolidone/vinyl acetate (PVP-VA), on the dissolution behaviour of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analysed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and non-sink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by pre-dissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

show abstract

“…Functionals that take account of dispersion forces have particularly allowed normal mode simulations with unprecedented accuracy . Frequency calculations have been reported in a broad spectrum of systems, including explosives, hydrocarbons, pharmaceuticals, and biomolecules …”

Section: Introductionmentioning

confidence: 99%

“…Functionals that take account of dispersion forces have particularly allowed normal mode simulations with unprecedented accuracy. [41][42][43][44] Frequency calculations have been reported in a broad spectrum of systems, including explosives, 45 hydrocarbons, 23,39,46 pharmaceuticals, [47][48][49][50] and biomolecules. 40,43,44,[51][52][53][54][55][56][57][58] Given the impact of THz spectroscopy and ab initio DFT simulations, we have systematically investigated the basic structure of molecular phonon modes.…”

Section: Introductionmentioning

confidence: 99%

Mixing of intermolecular and intramolecular vibrations in optical phonon modes: terahertz spectroscopy and solid‐state density functional theory

Zhang

Wang

Tominaga

et al. 2016

WIREs Comput Mol Sci

View full text Add to dashboard Cite

Conformational origins of polymorphism in two forms of flufenamic acid

Cited by 27 publications

References 34 publications

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

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

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

Mixing of intermolecular and intramolecular vibrations in optical phonon modes: terahertz spectroscopy and solid‐state density functional theory

Contact Info

Product

Resources

About