The Experts below are selected from a list of 1596 Experts worldwide ranked by ideXlab platform
Colin C Seaton - One of the best experts on this subject based on the ideXlab platform.
-
thermal behavior of benzoic acid Isonicotinamide binary cocrystals
Crystal Growth & Design, 2015Co-Authors: Asma B M Buanz, Colin C Seaton, Ian J. Scowen, Timothy J Prior, Jonathan C Burley, Bahijja Tolulope Raimiabraham, Richard Telford, Michael Hart, Philip J Davies, Simon GaisfordAbstract:A comprehensive study of the thermal behavior of the 1:1 and 2:1 benzoic acid/Isonicotinamide cocrystals is reported. The 1:1 material shows a simple unit cell expansion followed by melting upon heating. The 2:1 crystal exhibits more complex behavior. Its unit cell first expands upon heating, as a result of C–H···π interactions being lengthened. It then is converted into the 1:1 crystal, as demonstrated by significant changes in its X-ray diffraction pattern. The loss of 1 equiv of benzoic acid is confirmed by thermogravimetric analysis–mass spectrometry. Hot stage microscopy confirms that, as intuitively expected, the transformation begins at the crystal surface. The temperature at which conversion occurs is highly dependent on the sample mass and geometry, being reduced when the sample is under a gas flow or has a greater exposed surface area but increased when the heating rate is elevated.
-
solubility metastable zone width measurement and crystal growth of the 1 1 benzoic acid Isonicotinamide cocrystal in solutions of variable stoichiometry
Journal of Pharmaceutical Sciences, 2010Co-Authors: Sarah Boyd, Kevin Back, Keith Chadwick, Roger J Davey, Colin C SeatonAbstract:The solubility and crystal growth of the 1:1 cocrystal between benzoic acid and Isonicotinamide from 95% ethanol was studied through the creation of a ternary phase diagram at differing temperatures and turbidity measurements. From the solubility measurements thermodynamic properties of the system were evaluated, which indicate little solution binding of the two components supported by in situ FT-IR spectra. Cooling crystallisation from solutions of differing composition suggests differing crystal growth characteristics. An excess of benzoic acid appears to increase the metastable zone width and reduce the crystal size through interactions along the fastest growth axis, while an excess of Isonicotinamide decreases the metastable zone width with increased crystal size.
-
controlling the formation of benzoic acid Isonicotinamide molecular complexes
Crystal Growth & Design, 2009Co-Authors: Colin C Seaton, Andrew Parkin, Chick C Wilson, Nicholas BlagdenAbstract:The formation of crystalline molecular complexes of benzoic acid and Isonicotinamide with 1:1 and 2:1 compositions has been investigated through solution cocrystallization. The 1:1 complex was solely obtained from ethanol solutions, while either complex could be grown from aqueous and methanol solution by variation of the initial composition. The crystal structures of the 2:1 complex and a monohydrate of Isonicotinamide were determined by single crystal X-ray diffraction. The intermolecular interactions in the crystal structure of the complex were compared with other published carboxylic acid:Isonicotinamide molecular complexes, which highlights the robust nature of the acid···pyridine and acid···amide hydrogen bond, which exist in most cases. Complementary computational studies into the binding of pairs of these molecules by ab initio calculations were found to support the experimental observations and highlight the role of solvent in controlling the final crystalline form for multicomponent systems, through altering the hierarchy of intermolecular interactions.
Ricardo A. E. Castro - One of the best experts on this subject based on the ideXlab platform.
-
Thermal studies, degradation kinetic, equilibrium solubility, DFT, MIR, and XRPD analyses of a new cocrystal of gemfibrozil and Isonicotinamide
Journal of Thermal Analysis and Calorimetry, 2019Co-Authors: Bruno B. C. Holanda, Rafael Turra Alarcon, Caroline Gaglieri, Aguinaldo R. Souza, Paulo C. P. Rosa, Débora J. A. Tangerino, Ricardo A. E. Castro, Gilbert BannachAbstract:A synthesis of a novel pharmaceutical cocrystal of the gemfibrozil (GEM) with the Isonicotinamide (INCT) as coformer was carried out using the mechanochemical method of solvent drop grinding. The cocrystal formation was evidenced using the X-Ray powder diffraction, medium infrared spectroscopy, computational methods (DFT), simultaneous thermogravimetric-differential thermal analysis (TG/DTG–DTA), and differential scanning calorimetry. The association of techniques used to analyze all proportion synthetized (GEM:INCT—5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5) showed formation of the cocrystal in the proportion of 1 mol:1 mol. Furthermore, kinetic studies were performed to determine the stability of the cocrystal formed, possible shelf time (5% degradation), and best storage temperature. The dissolution profiles of GEM and GEM:INCT were collected using 0.1 M HCl, pH 4.5 sodium acetate buffer, water, and potassium phosphate buffer at pH 5.8, pH 6.8, and pH 7.4. The results demonstrate that the cocrystal exhibits superior apparent maximum solubility relative to the pure drug with a high solubility in alkaline environment. Finally, the study shows that the cocrystal of gemfibrozil with Isonicotinamide can be applied in new solid oral dosage formulations of enhanced bioavailability.
-
binary phase diagrams of pyridinecarboxamide isomers
Journal of Thermal Analysis and Calorimetry, 2017Co-Authors: Ana M Cortesao, Ricardo A. E. Castro, Joao G Henriques, João Canotilho, Teresa M. R. Maria, Ermelinda M S EusebioAbstract:Pyridinecarboxamide binary phase diagrams have been established using differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. Simulated diagrams obtained using with the Schroder-van Laar and Prigogine–Defay equations are in very good agreement with experimental data. The binary systems nicotinamide (Form I)–picolinamide (Form II) and Isonicotinamide (Form II)—picolinamide (Form I and Form II) occur as eutectic mixtures. Nicotinamide (Form I)—Isonicotinamide (Forms II and Form I) solid–liquid phase diagram confirms formation of the cocrystal with molar ratio of 1:1, whose crystal structure was already solved by Bathori et al. (Cryst Growth Des 11:75–87, 12) with X-ray diffraction on single crystals obtained by crystallization from common solution of nicotinamide and Isonicotinamide. The corresponding eutectic composition and temperatures, beyond polymorphism of Isonicotinamide and picolinamide under these molecular environments are discussed.
-
Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution
CrystEngComm, 2016Co-Authors: António O. L. Évora, Ricardo A. E. Castro, J.h. Ter Horst, João Canotilho, Teresa M. R. Maria, M. Ramos Silva, M. Ermelinda S. EusébioAbstract:Diflunisal is an anti-inflammatory, non-steroidal drug, class II of the Biopharmaceutical Classification System, which has recently been the subject of renewed interest due to its potential for use in the oral therapy of familial amyloid polyneuropathy. In this study, a thermodynamics based approach is used to investigate binary mixtures (diflunisal + picolinamide and diflunisal + Isonicotinamide) in order to identify solid forms that are potentially useful to improve the biopharmaceutical performance of this active pharmaceutical ingredient. Special emphasis is placed on the research of co-crystals and on the influence of structural changes in the pyridinecarboxamide co-former molecules for co-crystal formation with diflunisal. The thermodynamics based methodology described by ter Horst et al. in 2010 indicates that the formation of co-crystals is thermodynamically feasible for both systems. The binary solid–liquid phase diagrams were built and allowed unequivocal identification of the formation of co-crystals of diflunisal with each of the two isomers and also their stoichiometry of 1 : 1, (diflunisal : co-former) in the case of pyridine-2-carboxamide (picolinamide) and (2 : 1) for pyridine-4-carboxamide (Isonicotinamide). Two binary eutectic mixtures, potentially relevant for pharmaceutical application, were also identified. Infrared spectroscopy allowed the identification of the acid⋯N-pyridine heterosynthon in the three co-crystals formed by diflunisal with the isomeric pyridinecarboxamides. However, the results clearly differentiated pyridine-2-carboxamide from pyridine-3-carboxamide and pyridine-4-carboxamide, that share similar crystalline arrangements, at least with respect to the supramolecular synthons.
-
co crystals of diflunisal and isomeric pyridinecarboxamides a thermodynamics and crystal engineering contribution
CrystEngComm, 2016Co-Authors: António O. L. Évora, Ricardo A. E. Castro, João Canotilho, Teresa M. R. Maria, Ramos M Silva, J H Ter Horst, Ermelinda M S EusebioAbstract:Diflunisal is an anti-inflammatory, non-steroidal drug, class II of the Biopharmaceutical Classification System, which has recently been the subject of renewed interest due to its potential for use in the oral therapy of familial amyloid polyneuropathy. In this study, a thermodynamics based approach is used to investigate binary mixtures (diflunisal + picolinamide and diflunisal + Isonicotinamide) in order to identify solid forms that are potentially useful to improve the biopharmaceutical performance of this active pharmaceutical ingredient. Special emphasis is placed on the research of co-crystals and on the influence of structural changes in the pyridinecarboxamide co-former molecules for co-crystal formation with diflunisal. The thermodynamics based methodology described by ter Horst et al. in 2010 indicates that the formation of co-crystals is thermodynamically feasible for both systems. The binary solid–liquid phase diagrams were built and allowed unequivocal identification of the formation of co-crystals of diflunisal with each of the two isomers and also their stoichiometry of 1 : 1, (diflunisal : co-former) in the case of pyridine-2-carboxamide (picolinamide) and (2 : 1) for pyridine-4-carboxamide (Isonicotinamide). Two binary eutectic mixtures, potentially relevant for pharmaceutical application, were also identified. Infrared spectroscopy allowed the identification of the acid⋯N-pyridine heterosynthon in the three co-crystals formed by diflunisal with the isomeric pyridinecarboxamides. However, the results clearly differentiated pyridine-2-carboxamide from pyridine-3-carboxamide and pyridine-4-carboxamide, that share similar crystalline arrangements, at least with respect to the supramolecular synthons.
Gilbert Bannach - One of the best experts on this subject based on the ideXlab platform.
-
Thermal studies, degradation kinetic, equilibrium solubility, DFT, MIR, and XRPD analyses of a new cocrystal of gemfibrozil and Isonicotinamide
Journal of Thermal Analysis and Calorimetry, 2019Co-Authors: Bruno B. C. Holanda, Rafael Turra Alarcon, Caroline Gaglieri, Aguinaldo R. Souza, Paulo C. P. Rosa, Débora J. A. Tangerino, Ricardo A. E. Castro, Gilbert BannachAbstract:A synthesis of a novel pharmaceutical cocrystal of the gemfibrozil (GEM) with the Isonicotinamide (INCT) as coformer was carried out using the mechanochemical method of solvent drop grinding. The cocrystal formation was evidenced using the X-Ray powder diffraction, medium infrared spectroscopy, computational methods (DFT), simultaneous thermogravimetric-differential thermal analysis (TG/DTG–DTA), and differential scanning calorimetry. The association of techniques used to analyze all proportion synthetized (GEM:INCT—5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5) showed formation of the cocrystal in the proportion of 1 mol:1 mol. Furthermore, kinetic studies were performed to determine the stability of the cocrystal formed, possible shelf time (5% degradation), and best storage temperature. The dissolution profiles of GEM and GEM:INCT were collected using 0.1 M HCl, pH 4.5 sodium acetate buffer, water, and potassium phosphate buffer at pH 5.8, pH 6.8, and pH 7.4. The results demonstrate that the cocrystal exhibits superior apparent maximum solubility relative to the pure drug with a high solubility in alkaline environment. Finally, the study shows that the cocrystal of gemfibrozil with Isonicotinamide can be applied in new solid oral dosage formulations of enhanced bioavailability.
Ashwini Nangia - One of the best experts on this subject based on the ideXlab platform.
-
Modulating the solubility of sulfacetamide by means of cocrystals
CrystEngComm, 2014Co-Authors: N. Rajesh Goud, Ronaq Ali Khan, Ashwini NangiaAbstract:Sulfacetamide is a popular antibiotic prescribed for treating ocular infections. However, various physiological constraints are known to reduce its concentration at the site of action, thereby limiting its therapeutic efficacy. In this crystal engineering study, we report novel cocrystals of sulfacetamide with the objective to lower the solubility of the reference drug and improve its residence time at the site of action. Standard cocrystallization methods resulted in cocrystals with caffeine, Isonicotinamide, theophylline, bipyridine and a salt with 4-aminopyridine. These crystalline forms were characterized by thermal, spectroscopic and diffraction techniques. In pH 7 phosphate buffer medium, sulfacetamide–caffeine cocrystal exhibited lower solubility (8.64 g L−1, 0.69 times) than the drug (12.5 g L−1). The dissolution of sulfacetamide–Isonicotinamide and sulfacetamide–caffeine is 0.64 and 0.68 times lower, whereas sulfacetamide–theophylline is comparable to the reference drug. This study highlights a less explored application of pharmaceutical cocrystals to reduce the solubility and dissolution rate of the drug for improved therapeutic action.
-
pharmaceutical cocrystals of niclosamide
Crystal Growth & Design, 2012Co-Authors: Palash Sanphui, Sudalai S Kumar, Ashwini NangiaAbstract:Niclosamide (NCL) is an anthelmintic BCS class II drug of low solubility and high permeability. Pharmaceutical cocrystals of NCL were prepared with GRAS molecules, such as caffeine (CAF), urea (URE), p-aminobenzoic acid (PABA), theophylline (THPH), nicotinamide (NCT), and Isonicotinamide (INA), to improve drug solubility. Neat grinding, wet granulation, and slow evaporation methods were successful to make niclosamide cocrystals. All new crystalline forms were characterized by X-ray diffraction, differential scanning calorimetry, and IR-Raman spectroscopy to confirm their purity and homogeneity. X-ray crystal structures provided details of hydrogen bonding, molecular packing, and drug···coformer interactions. The intermolecular O–H···O hydrogen bond from the hydroxyl donor to the carbonyl acceptor in the niclosamide crystal structure was replaced by an acceptor atom of the coformer in cocrystal structures. Cocrystals with nicotinamide and Isonicotinamide were characterized by 13C ss-NMR spectroscopy becaus...
-
1 2 and 1 1 ag i Isonicotinamide coordination compounds five fold interpenetrated cdso4 network and the first example of pyridine n ag o amide bonds
Crystal Growth & Design, 2004Co-Authors: Balakrishna R Bhogala, Praveen K Thallapally, Ashwini NangiaAbstract:On the basis of acid−pyridine and acid−amide hydrogen bond synthons in dicarboxylic acid−Isonicotinamide complexes and proton/silver mimicry in carboxylic acids, Isonicotinamide was reacted with AgBF4 to afford different coordination compounds. The crystal structure of [Ag(C5H4NCONH2)2][BF4] 1 has linear tapes of Npyridyl−Ag−Npyridyl (180.0°) connected via N−H···O and N−H···F hydrogen bonds in square nets with CdSO4 topology. The 16 × 17 A voids eschew 5-fold interpenetration of identical nets. [Ag(C5H4NCONH2)][BF4] 2 provides the first occurrence of near linear Npyridyl−Ag−Oamide bonds (165.4°). The similarity in motifs of carboxylic acid and Ag(I) is extended to heterosynthons for crystal engineering.
-
supramolecular synthons in phenol Isonicotinamide adducts
CrystEngComm, 2003Co-Authors: Peddy Vishweshwar, Ashwini Nangia, Vincent M LynchAbstract:Molecular complexes of four phenols (hydroquinone, resorcinol, phloroglucinol and 4-hydroxybenzoic acid) with Isonicotinamide are characterized by X-ray diffraction. (Hydroquinone)0.5·(Isonicotinamide) 1 and (resorcinol)·(Isonicotinamide)22 have tapes of O–H⋯N and amide N–H⋯O dimer synthons. In (phloroglucinol)·(Isonicotinamide)2·(H2O)23, six component self-assembly results in stacked dimers with four O–H⋯N and four amide N–H⋯O hydrogen bonds and the third phenol OH aggregates with two water molecules in a supramolecular chair cyclohexane array. Phenol⋯pyridine and amide N–H⋯O dimers are robust synthons in 1–3 for the self-assembly of 0D discrete aggregates and infinite 1D chains. Hydrogen bonding of amide dimers via N–H⋯Ophenol/water is ascribed to cooperative effects. The crystal structure of (4-hydroxybenzoic acid)·(Isonicotinamide) 4 establishes the robustness of phenol⋯pyridine hydrogen bonding in the presence of carboxylic acid groups. Molecular components in 4 are arranged as zigzag tapes of O–H⋯N hydrogen bonds and acid⋯amide heterodimers. Supramolecular synthesis with phenol–Isonicotinamide adducts expands the versatility of Isonicotinamide as a co-crystallizing agent in crystal engineering.
Duncan I Jodrell - One of the best experts on this subject based on the ideXlab platform.
-
inhibition of cancer cell growth by ruthenium ii arene complexes
Journal of Medicinal Chemistry, 2001Co-Authors: Robert Edward Morris, Simon Parsons, Andrew Parkin, Rhona E Aird, Piedad Del Socorro Murdoch, Haimei Chen, Jeffrey Cummings, Nathan D Hughes, Gary Boyd, Duncan I JodrellAbstract:Inhibition of the growth of the human ovarian cancer cell line A2780 by organometallic ruthenium(II) complexes of the type [(η6-arene)Ru(X)(Y)(Z)], where arene is benzene or substituted benzene, X, Y, and Z are halide, acetonitrile, or Isonicotinamide, or X,Y is ethylenediamine (en) or N-ethylethylenediamine, has been investigated. The X-ray crystal structures of the complexes [(η6-p-cymene)Ru(en)Cl]PF6 (5), [(η6-p-cymene)RuCl2(Isonicotinamide)] (7), and [(η6-biphenyl)Ru(en)Cl]PF6 (9) are reported. They have “piano stool” geometries with η6 coordination of the arene ligand. Complexes with X,Y as a chelated en ligand and Z as a monofunctional leaving group had the highest activity. Complexes 5, 6 (the iodo analogue of 5), 9, and 10 (ethylethylenediamine analogue of 9) were as active as carboplatin. Hydrolysis of the reactive Ru−Cl bond in complex 5 was detected by HPLC but was suppressed by the addition of chloride ions. Complex 5 binds strongly and selectively to G bases on DNA oligonucleotides to form mo...
-
inhibition of cancer cell growth by ruthenium ii arene complexes
Journal of Medicinal Chemistry, 2001Co-Authors: Robert Edward Balintemple Morris, Simon Parsons, Andrew Parkin, Rhona E Aird, Piedad Del Socorro Murdoch, Haimei Chen, Jeffrey Cummings, Nathan D Hughes, Gary Boyd, Duncan I JodrellAbstract:Inhibition of the growth of the human ovarian cancer cell line A2780 by organometallic ruthenium(II) complexes of the type [(eta(6)-arene)Ru(X)(Y)(Z)], where arene is benzene or substituted benzene, X, Y, and Z are halide, acetonitrile, or Isonicotinamide, or X,Y is ethylenediamine (en) or N-ethylethylenediamine, has been investigated. The X-ray crystal structures of the complexes [(eta(6)-p-cymene)Ru(en)Cl]PF(6) (5), [(eta(6)-p-cymene)RuCl(2)(Isonicotinamide)] (7), and [(eta(6)-biphenyl)Ru(en)Cl]PF(6) (9) are reported. They have "piano stool" geometries with eta(6) coordination of the arene ligand. Complexes with X,Y as a chelated en ligand and Z as a monofunctional leaving group had the highest activity. Complexes 5, 6 (the iodo analogue of 5), 9, and 10 (ethylethylenediamine analogue of 9) were as active as carboplatin. Hydrolysis of the reactive Ru-Cl bond in complex 5 was detected by HPLC but was suppressed by the addition of chloride ions. Complex 5 binds strongly and selectively to G bases on DNA oligonucleotides to form monofunctional adducts. No inhibition of topoisomerase I or II by complexes 5, 6, or 9 was detected. These chelated Ru(II) arene complexes have potential as novel metal-based anticancer agents with a mechanism of action different from that of the Ru(III) complex currently on clinical trial.
