14 research outputs found
Nitazoxanide Cocrystals in Combination with Succinic, Glutaric, and 2,5-Dihydroxybenzoic Acid
Combination of nitazoxanide (NTZ)
with a total of 32 cocrystal
formers gave cocrystals with succinic acid (NTZ-SUC, 2:1) and glutaric
acid (NTZ-GLU, 1:1). Additionally, 2,5-dihydroxybenzoic acid provided
a cocrystal solvate with acetonitrile (NTZ-25DHBA-CH<sub>3</sub>CN,
1:1:1). All solid phases were characterized by X-ray powder diffraction
analysis, IR spectroscopy, thermogravimetric analysis, differential
scanning calorimetry, and single-crystal X-ray diffraction analysis.
Single-crystal X-ray crystallography revealed that NTZ and the carboxylic
acid cocrystal formers were linked in all three cocrystals through
the same supramolecular heterodimeric synthon, C(N)NH···HOOC.
Despite having different stoichiometries, the crystal structures of
NTZ-SUC and NTZ-GLU showed similarities in the supramolecular organization,
both containing two-dimensional layers formed by NTZ molecules, which
were further interconnected by single (NTZ-SUC) and homodimeric entities
(NTZ-GLU) of the cocrystal former. Basic physical stability tests
showed that cocrystals NTZ-SUC and NTZ-GLU are stable at least for
one month under standardized temperature/relative humidity stress
conditions but decompose within 1 h into the corresponding physical
phase mixtures, when exposed to aqueous solutions simulating physiological
gastrointestinal conditions. Measurement of the dissolution rates
gave small increases of the intrinsic dissolution rate constants when
compared with NTZ. Pressure stability tests showed that the cocrystals
support higher pressures (at least up to 60 kg/cm<sup>2</sup>) than
NTZ
Nitazoxanide Cocrystals in Combination with Succinic, Glutaric, and 2,5-Dihydroxybenzoic Acid
Combination of nitazoxanide (NTZ)
with a total of 32 cocrystal
formers gave cocrystals with succinic acid (NTZ-SUC, 2:1) and glutaric
acid (NTZ-GLU, 1:1). Additionally, 2,5-dihydroxybenzoic acid provided
a cocrystal solvate with acetonitrile (NTZ-25DHBA-CH<sub>3</sub>CN,
1:1:1). All solid phases were characterized by X-ray powder diffraction
analysis, IR spectroscopy, thermogravimetric analysis, differential
scanning calorimetry, and single-crystal X-ray diffraction analysis.
Single-crystal X-ray crystallography revealed that NTZ and the carboxylic
acid cocrystal formers were linked in all three cocrystals through
the same supramolecular heterodimeric synthon, C(N)NH···HOOC.
Despite having different stoichiometries, the crystal structures of
NTZ-SUC and NTZ-GLU showed similarities in the supramolecular organization,
both containing two-dimensional layers formed by NTZ molecules, which
were further interconnected by single (NTZ-SUC) and homodimeric entities
(NTZ-GLU) of the cocrystal former. Basic physical stability tests
showed that cocrystals NTZ-SUC and NTZ-GLU are stable at least for
one month under standardized temperature/relative humidity stress
conditions but decompose within 1 h into the corresponding physical
phase mixtures, when exposed to aqueous solutions simulating physiological
gastrointestinal conditions. Measurement of the dissolution rates
gave small increases of the intrinsic dissolution rate constants when
compared with NTZ. Pressure stability tests showed that the cocrystals
support higher pressures (at least up to 60 kg/cm<sup>2</sup>) than
NTZ
Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
Acetazolamide (ACZ) has been combined via liquid-assisted
grinding
in water with a library of cocrystal formers derived from benzoic
and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide,
2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The
cocrystalline phases were identified first by XRPD analysis and then
structurally characterized by IR spectroscopy and single-crystal X-ray
diffraction analysis. These cocrystals and the previously reported
cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide
constitute a series of six cocrystals of varied stoichiometric ratios
(3:1, 2:1, 1:1, and 1:2), which allowed for a profound analysis of
the structural and chemical factors that govern their formation. The
structural analysis has shown that the ACZ molecules participate in
the dominant hydrogen-bonding patterns within the crystal structures:
three cocrystal structures exhibit extended supramolecular aggregates
of ACZ having channels, pores, or semispherical voids, in which the
cocrystal formers are included as guest molecules, and can, therefore,
be described as inclusion or clathrate complexes. One cocrystal can
be considered as a pillared or intercalation compound, and the remaining
two cocrystals are true two-component 2D or 3D networks. In addition,
a variety of alternative preparative methods (liquid-assisted grinding,
neat grinding, reaction crystallization, solution-mediated phase transformation,
and solution crystallization) have been employed, showing that four
of the six cocrystals required the presence of water for successful
cocrystal formation
Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
Acetazolamide (ACZ) has been combined via liquid-assisted
grinding
in water with a library of cocrystal formers derived from benzoic
and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide,
2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The
cocrystalline phases were identified first by XRPD analysis and then
structurally characterized by IR spectroscopy and single-crystal X-ray
diffraction analysis. These cocrystals and the previously reported
cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide
constitute a series of six cocrystals of varied stoichiometric ratios
(3:1, 2:1, 1:1, and 1:2), which allowed for a profound analysis of
the structural and chemical factors that govern their formation. The
structural analysis has shown that the ACZ molecules participate in
the dominant hydrogen-bonding patterns within the crystal structures:
three cocrystal structures exhibit extended supramolecular aggregates
of ACZ having channels, pores, or semispherical voids, in which the
cocrystal formers are included as guest molecules, and can, therefore,
be described as inclusion or clathrate complexes. One cocrystal can
be considered as a pillared or intercalation compound, and the remaining
two cocrystals are true two-component 2D or 3D networks. In addition,
a variety of alternative preparative methods (liquid-assisted grinding,
neat grinding, reaction crystallization, solution-mediated phase transformation,
and solution crystallization) have been employed, showing that four
of the six cocrystals required the presence of water for successful
cocrystal formation
Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
Acetazolamide (ACZ) has been combined via liquid-assisted
grinding
in water with a library of cocrystal formers derived from benzoic
and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide,
2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The
cocrystalline phases were identified first by XRPD analysis and then
structurally characterized by IR spectroscopy and single-crystal X-ray
diffraction analysis. These cocrystals and the previously reported
cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide
constitute a series of six cocrystals of varied stoichiometric ratios
(3:1, 2:1, 1:1, and 1:2), which allowed for a profound analysis of
the structural and chemical factors that govern their formation. The
structural analysis has shown that the ACZ molecules participate in
the dominant hydrogen-bonding patterns within the crystal structures:
three cocrystal structures exhibit extended supramolecular aggregates
of ACZ having channels, pores, or semispherical voids, in which the
cocrystal formers are included as guest molecules, and can, therefore,
be described as inclusion or clathrate complexes. One cocrystal can
be considered as a pillared or intercalation compound, and the remaining
two cocrystals are true two-component 2D or 3D networks. In addition,
a variety of alternative preparative methods (liquid-assisted grinding,
neat grinding, reaction crystallization, solution-mediated phase transformation,
and solution crystallization) have been employed, showing that four
of the six cocrystals required the presence of water for successful
cocrystal formation
Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
Acetazolamide (ACZ) has been combined via liquid-assisted
grinding
in water with a library of cocrystal formers derived from benzoic
and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide,
2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The
cocrystalline phases were identified first by XRPD analysis and then
structurally characterized by IR spectroscopy and single-crystal X-ray
diffraction analysis. These cocrystals and the previously reported
cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide
constitute a series of six cocrystals of varied stoichiometric ratios
(3:1, 2:1, 1:1, and 1:2), which allowed for a profound analysis of
the structural and chemical factors that govern their formation. The
structural analysis has shown that the ACZ molecules participate in
the dominant hydrogen-bonding patterns within the crystal structures:
three cocrystal structures exhibit extended supramolecular aggregates
of ACZ having channels, pores, or semispherical voids, in which the
cocrystal formers are included as guest molecules, and can, therefore,
be described as inclusion or clathrate complexes. One cocrystal can
be considered as a pillared or intercalation compound, and the remaining
two cocrystals are true two-component 2D or 3D networks. In addition,
a variety of alternative preparative methods (liquid-assisted grinding,
neat grinding, reaction crystallization, solution-mediated phase transformation,
and solution crystallization) have been employed, showing that four
of the six cocrystals required the presence of water for successful
cocrystal formation
Modification of the Supramolecular Hydrogen-Bonding Patterns of Acetazolamide in the Presence of Different Cocrystal Formers: 3:1, 2:1, 1:1, and 1:2 Cocrystals from Screening with the Structural Isomers of Hydroxybenzoic Acids, Aminobenzoic Acids, Hydroxybenzamides, Aminobenzamides, Nicotinic Acids, Nicotinamides, and 2,3-Dihydroxybenzoic Acids
Acetazolamide (ACZ) has been combined via liquid-assisted
grinding
in water with a library of cocrystal formers derived from benzoic
and nicotinic acid, which provided novel cocrystals with 2-hydroxybenzamide,
2-aminobenzamide, picolinamide, and 2,3-dihydroxybenzoic acid. The
cocrystalline phases were identified first by XRPD analysis and then
structurally characterized by IR spectroscopy and single-crystal X-ray
diffraction analysis. These cocrystals and the previously reported
cocrystalline phases obtained from 4-hydroxybenzoic acid and nicotinamide
constitute a series of six cocrystals of varied stoichiometric ratios
(3:1, 2:1, 1:1, and 1:2), which allowed for a profound analysis of
the structural and chemical factors that govern their formation. The
structural analysis has shown that the ACZ molecules participate in
the dominant hydrogen-bonding patterns within the crystal structures:
three cocrystal structures exhibit extended supramolecular aggregates
of ACZ having channels, pores, or semispherical voids, in which the
cocrystal formers are included as guest molecules, and can, therefore,
be described as inclusion or clathrate complexes. One cocrystal can
be considered as a pillared or intercalation compound, and the remaining
two cocrystals are true two-component 2D or 3D networks. In addition,
a variety of alternative preparative methods (liquid-assisted grinding,
neat grinding, reaction crystallization, solution-mediated phase transformation,
and solution crystallization) have been employed, showing that four
of the six cocrystals required the presence of water for successful
cocrystal formation
Selective Isolation of Polycyclic Aromatic Hydrocarbons by Self-Assembly of a Tunable N→B Clathrate
The combination of one dipyridyl
linker [1,2-di(4-pyridyl)ethylene
(DPE), 1,2-di(4-pyridyl)ethane (DPEt), or 4,4′-azopyridine
(DPA)] with two molecules of arylboronate ester <b>1</b> produced
dinuclear Lewis-type N→B adducts that can act as acyclic host
for polycyclic aromatic hydrocarbons (PAHs) in the solid state. Nine
crystalline solids of composition PAH@adduct (i.e., one PAH per adduct)
were obtained from solutions containing a single PAH. On the basis
of the single-crystal X-ray diffraction analysis of the compound ANT@A1
(ANT = anthracene; A1 = adduct being composed of DPE and two boronate
esters <b>1</b>), the PAH inclusion selectivity is related to
a size-fitting adaptation to an octaedral-shaped pocket assembled
by CH-π interactions between fragments of the diamine and the
arylboronate ester <b>1</b>. The resulting reversible organic
clathrates can perform “catch and release” cycles of
PAHs such as pyrene and can sequester selectively PAHs from mixtures
in solution
Selective Isolation of Polycyclic Aromatic Hydrocarbons by Self-Assembly of a Tunable N→B Clathrate
The combination of one dipyridyl
linker [1,2-di(4-pyridyl)ethylene
(DPE), 1,2-di(4-pyridyl)ethane (DPEt), or 4,4′-azopyridine
(DPA)] with two molecules of arylboronate ester <b>1</b> produced
dinuclear Lewis-type N→B adducts that can act as acyclic host
for polycyclic aromatic hydrocarbons (PAHs) in the solid state. Nine
crystalline solids of composition PAH@adduct (i.e., one PAH per adduct)
were obtained from solutions containing a single PAH. On the basis
of the single-crystal X-ray diffraction analysis of the compound ANT@A1
(ANT = anthracene; A1 = adduct being composed of DPE and two boronate
esters <b>1</b>), the PAH inclusion selectivity is related to
a size-fitting adaptation to an octaedral-shaped pocket assembled
by CH-π interactions between fragments of the diamine and the
arylboronate ester <b>1</b>. The resulting reversible organic
clathrates can perform “catch and release” cycles of
PAHs such as pyrene and can sequester selectively PAHs from mixtures
in solution
A Twist in Cocrystals of Salts: Changes in Packing and Chloride Coordination Lead to Opposite Trends in the Biopharmaceutical Performance of Fluoroquinolone Hydrochloride Cocrystals
Fluoroquinolones are extensively
used antibiotics that are generally
prescribed as hydrochloride salts because the neutral forms display
low solubility due to their zwitterionic character. Starting from
the hydrochloride salts of ciprofloxacin (CiHCl) or (<i>S</i>,<i>S</i>)-moxifloxacin (MoHCl) and 4-hydroxybenzoic acid
(4HBA) as a cocrystal former, two cocrystalline solids, CiHCl–4HBA
and MoHCl–4HBA, were obtained in a salt/coformer stoichiometric
ratio of 1:1. The cocrystalline phases were identified by X-ray powder
diffraction analysis and further characterized by IR spectroscopy,
thermogravimetric analysis-differential scanning calorimetry, and
single crystal X-ray diffraction analysis. The novel solid phases
could be formed using different methodologies, namely, solution-mediated
phase transformation, solvent drop grinding, crystallization by solvent
evaporation, and reaction crystallization. Pharmaceutically relevant
properties such as phase stability, thermodynamic solubility, and
dissolution rate were examined. All cocrystalline phases remained
stable when suspended in acidic aqueous solutions and did not transform
upon accelerated temperature/relative humidity exposition for 30 days.
Interestingly, opposite trends in the thermal stability, solubility,
and dissolution rate of the cocrystals were exhibited by the different
fluoroquinolones in comparison to the parent starting salts. Upon
heating, the CiHCl–4HBA cocrystal releases first the coformer
before decomposing and displayed a lower solubility and dissolution
rate in comparison to CiHCl·1.34H<sub>2</sub>O. By contrast,
the MoHCl–4HBA cocrystal melts in a single-phase transition
process and showed enhanced solubility and dissolution rate when compared
to the parent moxifloxacin salt. The similar composition of the cocrystals
and the structural resemblance of the fluoroquinolones examined herein
allowed for a detailed vis-à-vis comparison between the supramolecular
structures in the solid-state and the physicochemical properties.
The incorporation of 4HBA in the crystal lattice caused changes in
the number, type, and strength of the intermolecular interactions
between the ionic components (chloride and fluoroquinolinium cations),
which could be related to the solubility and dissolution rate properties.
While the cocrystal CiHCl–4HBA retained essential features
of the supramolecular assembly found also for the starting hydrochloride
and gave an overall three-dimensional hydrogen bonded network with
the cocrystal former, MoHCl–4HBA showed a singular two-dimensional
assembly, with linear chains formed between the 4HBA molecules and
chloride ions through O–H···Cl<sup>–</sup>···H–O hydrogen bonds in place of the usual
charged-assisted N<sup>+</sup>–H···Cl<sup>–</sup> interactions