5 research outputs found
Naproxen–Nicotinamide Cocrystals: Racemic and Conglomerate Structures Generated by CO<sub>2</sub> Antisolvent Crystallization
Cocrystallization of naproxen racemic
mixture and nicotinamide
was investigated in this work, using compressed CO<sub>2</sub> as
antisolvent. A novel racemic cocrystal structure containing both enantiomers
of naproxen linked to nicotinamide has been produced thanks to the
CO<sub>2</sub> antisolvent batch crystallization process. The structure
of the molecular complex and its intermolecular interactions were
investigated by single-crystal X-ray diffraction and attenuated total
reflectance Fourier transform infrared spectroscopy. The antisolvent
feed rate was found to have a direct influence on the cocrystallization
outcome. The racemic cocrystal was obtained at slow and moderate CO<sub>2</sub> feed rate, while very fast introduction of CO<sub>2</sub> resulted in the formation of a mixture of chiral cocrystals (conglomerate).
Cross-seedings, thermal analysis, and temperature-resolved X-ray powder
diffraction were used to probe the relationship between the different
phases. In addition, all powders produced with CO<sub>2</sub> technology
were obtained as cocrystal-pure, without significant excess of naproxen
or nicotinamide homocrystals
Mechanisms of Reversible Phase Transitions in Molecular Crystals: Case of Ciclopirox
The detailed characterization
of several subambient solid state
transitions occurring in the pharmaceutical ingredient Ciclopirox
between −20 °C and −85 °C was performed by
using a combination of DSC, cold-stage optical microscopy, vibrational
spectroscopies, solid state NMR at controlled temperature, structural
analyses by single crystal X-ray diffraction, and temperature-resolved
X-ray powder diffraction. The global analysis of the available data
reveals that the mechanisms of these reversible transitions involve
a subtle compromise between phenomena related to molecular disorder,
cooperative release of strains induced by cooling, and structural
reorganization associated with topotactic changes in crystal lattice
and symmetry. However, no major change in the main features of crystal
packings is observed during the successive single crystal-to-single
crystal transitions, which highlights the difficulty to classify such
transitions in the frame of conventional theoretical frameworks. The
successive thermal events and related structural changes or relaxations
can be seen as the consequences of a deconvolution phenomenon for
the global phase transition between the dynamically disordered room
temperature form (<i>C</i>2/<i>c</i>, Z = 8, Z′
= 1) and the ordered low-temperature form (<i>P</i>2<sub>1</sub>/<i>c</i>, Z = 48, Z′ = 12). In this respect,
the intermediate form(s) can be seen as transient states of kinetic
origin with a questionable genuine crystallographic relevance
Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches
In this article, we conduct a comprehensive
molecular relaxation
study of amorphous Quinidine above and below the glass-transition
temperature (<i>T</i><sub>g</sub>) through broadband dielectric
relaxation spectroscopy (BDS) experiments and theoretical density
functional theory (DFT) calculations, as one major issue with the
amorphous state of pharmaceuticals is life expectancy. These techniques
enabled us to determine what kind of molecular motions are responsible,
or not, for the devitrification of Quinidine. Parameters describing
the complex molecular dynamics of amorphous Quinidine, such as <i>T</i><sub>g</sub>, the width of the α relaxation (β<sub>KWW</sub>), the temperature dependence of α-relaxation times
(τ<sub>α</sub>), the fragility index (<i>m</i>), and the apparent activation energy of secondary γ relaxation
(<i>E</i><sub>a‑γ</sub>), were characterized.
Above <i>T</i><sub>g</sub> (> 60 °C), a medium degree
of nonexponentiality (β<sub>KWW</sub> = 0.5) was evidenced.
An intermediate value of the fragility index (<i>m</i> =
86) enabled us to consider Quinidine as a glass former of medium fragility.
Below <i>T</i><sub>g</sub> (< 60 °C), one well-defined
secondary γ relaxation, with an apparent activation energy of <i>E</i><sub>a‑γ</sub> = 53.8 kJ/mol, was reported.
From theoretical DFT calculations, we identified the most reactive
part of Quinidine moieties through exploration of the potential energy
surface. We evidenced that the clearly visible γ process has
an intramolecular origin coming from the rotation of the CH(OH)C<sub>9</sub>H<sub>14</sub>N end group. An excess wing observed in amorphous
Quinidine was found to be an unresolved Johari–Goldstein relaxation.
These studies were supplemented by sub-<i>T</i><sub>g</sub> experimental evaluations of the life expectancy of amorphous Quinidine
by X-ray powder diffraction and differential scanning calorimetry.
We show that the difference between <i>T</i><sub>g</sub> and the onset temperature for crystallization, <i>T</i><sub>c</sub>, which is 30 K, is sufficiently large to avoid recrystallization
of amorphous Quinidine during 16 months of storage under ambient conditions
Enhanced Second Harmonic Generation from an Organic Self-Assembled Eutectic Binary Mixture: A Case Study with 3‑Nitrobenzoic and 3,5-Dinitrobenzoic Acids
This work illustrates the use of
powder second harmonic generation
(powder SHG), temperature-resolved second harmonic generation (TR-SHG),
and second harmonic generation microscopy (SHGM) in monophasic and
multiphasic sample studies. The commercial powder of 3,5-dinitrobenzoic
acid was found to exhibit a significant second harmonic generation
signal, whereas only two centrosymmetric polymorphic forms have been
reported for this compound. Second harmonic generation techniques
were used in combination with chromatography, differential scanning
calorimetry, and powder X-ray diffraction to show that the SHG activity
of 3,5-dinitrobenzoic acid powder originates from a chemical impurity
(3-nitrobenzoic acid) present in the commercial powder under the form
of a new metastable noncentrosymmetric polymorph. The metastable equilibria
between 3,5-dinitrobenzoic acid and 3-nitrobenzoic acid were studied,
and SHG analyses performed on crystallized binary mixtures showed
significant enhancements of the SHG signal compared to that of the
pure noncentrosymmetric phase. This is due to the formation of a suitable
eutectic microstructure that enables quasi phase matching (QPM). In
particular, powders from near-eutectic compositions exhibit SHG signals
up to 20 times higher than that of the powder containing pure 3-nitrobenzoic
acid noncentrosymmetric phase. This observation could provide the
basis for a new route to achieve new, efficient materials for second-order
frequency conversion
Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches
In this article, we conduct a comprehensive
molecular relaxation
study of amorphous Quinidine above and below the glass-transition
temperature (<i>T</i><sub>g</sub>) through broadband dielectric
relaxation spectroscopy (BDS) experiments and theoretical density
functional theory (DFT) calculations, as one major issue with the
amorphous state of pharmaceuticals is life expectancy. These techniques
enabled us to determine what kind of molecular motions are responsible,
or not, for the devitrification of Quinidine. Parameters describing
the complex molecular dynamics of amorphous Quinidine, such as <i>T</i><sub>g</sub>, the width of the α relaxation (β<sub>KWW</sub>), the temperature dependence of α-relaxation times
(τ<sub>α</sub>), the fragility index (<i>m</i>), and the apparent activation energy of secondary γ relaxation
(<i>E</i><sub>a‑γ</sub>), were characterized.
Above <i>T</i><sub>g</sub> (> 60 °C), a medium degree
of nonexponentiality (β<sub>KWW</sub> = 0.5) was evidenced.
An intermediate value of the fragility index (<i>m</i> =
86) enabled us to consider Quinidine as a glass former of medium fragility.
Below <i>T</i><sub>g</sub> (< 60 °C), one well-defined
secondary γ relaxation, with an apparent activation energy of <i>E</i><sub>a‑γ</sub> = 53.8 kJ/mol, was reported.
From theoretical DFT calculations, we identified the most reactive
part of Quinidine moieties through exploration of the potential energy
surface. We evidenced that the clearly visible γ process has
an intramolecular origin coming from the rotation of the CH(OH)C<sub>9</sub>H<sub>14</sub>N end group. An excess wing observed in amorphous
Quinidine was found to be an unresolved Johari–Goldstein relaxation.
These studies were supplemented by sub-<i>T</i><sub>g</sub> experimental evaluations of the life expectancy of amorphous Quinidine
by X-ray powder diffraction and differential scanning calorimetry.
We show that the difference between <i>T</i><sub>g</sub> and the onset temperature for crystallization, <i>T</i><sub>c</sub>, which is 30 K, is sufficiently large to avoid recrystallization
of amorphous Quinidine during 16 months of storage under ambient conditions