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Journal of Pharmaceutical and... Feb 2017Solvent free mechanochemical approach is utilized to synthesise new cocrystals of chrysin using supramolecular chemistry based upon reliable synthons. Chrysin, a flavone...
Solvent free mechanochemical approach is utilized to synthesise new cocrystals of chrysin using supramolecular chemistry based upon reliable synthons. Chrysin, a flavone nutraceutical with wide range of beneficial effects has critically low bioavailability on account of its poor aqueous solubility and consequently poor absorption from the gastrointestinal tract. The present study focuses on this critical aspect and has exploited non covalent interactions to prepare its cocrystals with cytosine and thiamine hydrochloride. Various techniques were used for characterization including Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR), Solid State NMR Spectroscopy (SSNMR) and Powder X-Ray Diffraction (PXRD). The molecules in the cocrystals crystallized in neutral forms and assembled in a molecular layer by means of hydrogen bonding which was confirmed by structural characterization. The cocrystals share a common supramolecular motif being the OH⋯N interaction, involving phenolic moiety of C7 functionality of the parent molecule. Approximately 3-4 fold increase in solubility and dissolution profile of cocrystals was observed which was further corroborated by improved in vitro and in vivo activities including antioxidant, antihaemolytic and anti-inflammatory thus, opening a new viable technique for the exploitation of useful phytonutrients.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Calorimetry, Differential Scanning; Crystallization; Drug Evaluation, Preclinical; Flavonoids; Magnetic Resonance Spectroscopy; Male; Powder Diffraction; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 27894779
DOI: 10.1016/j.jpba.2016.10.020 -
Journal of Pharmaceutical Sciences Nov 2020Florfenicol is an antimicrobial drug used in veterinary medicine and aquaculture. Two polymorphic forms called A and B have been reported in literature, but the relation...
Florfenicol is an antimicrobial drug used in veterinary medicine and aquaculture. Two polymorphic forms called A and B have been reported in literature, but the relation between these two forms are unknown. In order to get a better understanding of the behavior of solid florfenicol and the possible evolution from a metastable form to a stable one, an accurate thermodynamic study has been carried out by calorimetric measurements. For this purpose, temperatures and enthalpies of transition and of fusion of the stable and metastable forms have been measured by DSC. TGA has been used in view to detect the eventual existence of solvates which does not occur. In view to confirm the kind of transition, c measurements of the two forms have been performed with a C80 calorimeter. With these c values, it has been possible to determine the function of the variation of enthalpies as a function of temperature, ΔH = f (T). A study of the kinetic of transformation has been realized and is presented as well as the patterns of the X-ray powder diffraction from 295 to 426 K. This last approach confirms the crystal structure of form A of florfenicol previously reported in literature.
Topics: Calorimetry, Differential Scanning; Powder Diffraction; Thermodynamics; Thiamphenicol; X-Ray Diffraction
PubMed: 32721472
DOI: 10.1016/j.xphs.2020.07.017 -
Colloids and Surfaces. B, Biointerfaces Dec 2015Liquisolid technology is also known as powder solution technology and is the technique which deals with the solubility term. This technology has been used to modify the... (Review)
Review
Liquisolid technology is also known as powder solution technology and is the technique which deals with the solubility term. This technology has been used to modify the dissolution rate of many drugs. Using this technique, many drugs exhibited enhanced or retarded dissolution rate. Non-steroidal anti-inflammatory drugs are among the highly important medications whose bioavailability is affected by the lower dissolution rate. In order to enhance the dissolution rate and subsequently the bioavailability of some of these drugs, liquisolid technology was used. This study reviewed the application of this useful technique for enhancing the dissolution rate of these important drugs and also the obtained results have been discussed in more details.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Calorimetry, Differential Scanning; Drug Delivery Systems; Powder Diffraction; Solubility
PubMed: 26398143
DOI: 10.1016/j.colsurfb.2015.09.014 -
Acta Crystallographica. Section C,... Feb 2022The crystal structure of cynarine monohydrate (systematic name: 1,3-bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-4,5-dihydroxycyclohexane-1-carboxylic acid...
The crystal structure of cynarine monohydrate (systematic name: 1,3-bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-4,5-dihydroxycyclohexane-1-carboxylic acid monohydrate), CHO·HO, has been solved and refined using synchrotron powder X-ray diffraction data, and optimized using density functional techniques. Despite being purchased as anhydrous, cynarine crystallizes as a monohydrate and the crystal structure is characterized by alternating layers of hydrocarbon and hydrogen-bonding interactions parallel to the bc plane. Hydrogen bonds are significant in the crystal structure. The carboxylic acid group forms a strong intermolecular hydrogen bond to a hydroxy group of the quinic acid ring. Most of the hydroxy groups act as donors in O-H...O hydrogen bonding to carbonyl O atoms. One hydroxy group participates in bifurcated hydrogen bonds, one to a hydroxy group on the quinic acid ring and the other, an intramolecular interaction, to another hydroxy group. The powder pattern has been submitted to the International Centre for Diffraction Data (ICDD) for inclusion in the Powder Diffraction File (PDF-4).
Topics: Cinnamates; Crystallography, X-Ray; Hydrogen Bonding; Powder Diffraction; Powders; Synchrotrons; X-Ray Diffraction
PubMed: 35119388
DOI: 10.1107/S2053229622000687 -
Journal of Pharmaceutical and... Nov 2014In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical...
In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.
Topics: Ampicillin; Anti-Bacterial Agents; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Computer Simulation; Crystallization; Crystallography, X-Ray; Drug Stability; Hot Temperature; Molecular Structure; Phase Transition; Powder Diffraction; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Technology, Pharmaceutical; Thermogravimetry; Time Factors
PubMed: 25194347
DOI: 10.1016/j.jpba.2014.08.021 -
Molecules (Basel, Switzerland) May 2021The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and...
The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl--[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl--[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.
Topics: Calorimetry, Differential Scanning; Glipizide; Hypoglycemic Agents; Microscopy, Electron, Scanning; Powder Diffraction; Spectroscopy, Fourier Transform Infrared; Thermogravimetry
PubMed: 34073973
DOI: 10.3390/molecules26113142 -
Acta Crystallographica Section B,... Feb 2022Synthetic and naturally occurring forms of tricopper orthotellurate, CuTeO (the mineral mcalpineite) have been investigated by 3D electron diffraction (3D ED), X-ray...
Synthetic and naturally occurring forms of tricopper orthotellurate, CuTeO (the mineral mcalpineite) have been investigated by 3D electron diffraction (3D ED), X-ray powder diffraction (XRPD), Raman and infrared (IR) spectroscopic measurements. As a result of the diffraction analyses, CuTeO is shown to occur in two polytypes. The higher-symmetric CuTeO-1C polytype is cubic, space group Ia3, with a = 9.537 (1) Å and V = 867.4 (3) Å as reported in previous studies. The 1C polytype is a well characterized structure consisting of alternating layers of CuO octahedra and both CuO and TeO octahedra in a patchwork arrangement. The structure of the lower-symmetric orthorhombic CuTeO-2O polytype was determined for the first time in this study by 3D ED and verified by Rietveld refinement. The 2O polytype crystallizes in space group Pcca, with a = 9.745 (3) Å, b = 9.749 (2) Å, c = 9.771 (2) Å and V = 928.3 (4) Å. High-precision XRPD data were also collected on CuTeO-2O to verify the lower-symmetric structure by performing a Rietveld refinement. The resultant structure is identical to that determined by 3D ED, with unit-cell parameters a = 9.56157 (19) Å, b = 9.55853 (11) Å, c = 9.62891 (15) Å and V = 880.03 (2) Å. The lower symmetry of the 2O polytype is a consequence of a different cation ordering arrangement, which involves the movement of every second CuO and TeO octahedral layer by (1/4, 1/4, 0), leading to an offset of TeO and CuO octahedra in every second layer giving an ABAB* stacking arrangement. Syntheses of CuTeO showed that low-temperature (473 K) hydrothermal conditions generally produce the 2O polytype. XRPD measurements in combination with Raman spectroscopic analysis showed that most natural mcalpineite is the orthorhombic 2O polytype. Both XRPD and Raman spectroscopy measurements may be used to differentiate between the two polytypes of CuTeO. In Raman spectroscopy, CuTeO-1C has a single strong band around 730 cm, whereas CuTeO-2O shows a broad double maximum with bands centred around 692 and 742 cm.
Topics: Electrons; Powder Diffraction; Spectrophotometry, Infrared; Spectrum Analysis, Raman; X-Ray Diffraction
PubMed: 35129117
DOI: 10.1107/S2052520621013032 -
Pharmaceutical Research Dec 2023To synthesize and characterize new cocrystals of berberine chloride (BCl) for potential pharmaceutical tablet formulation.
PURPOSE
To synthesize and characterize new cocrystals of berberine chloride (BCl) for potential pharmaceutical tablet formulation.
METHODS
Solutions of BCl with each of three selected cocrystal formers, catechol (CAT), resorcinol (RES), and hydroquinone (HYQ) were slowly evaporated at room temperature to obtain crystals. Crystal structures were solved using single crystal X-ray diffraction. Bulk powders were characterized by powder X-ray diffraction, thermogravimetric-differential scanning calorimetry, FTIR, dynamic moisture sorption, and dissolution (both intrinsic and powder).
RESULTS
Single crystal structures confirmed the formation of cocrystals with all three coformers, which revealed various intermolecular interactions that stabilized crystal lattices, including O-H···Cl hydrogen bonds. All three cocrystals exhibited better stability against high humidity (up to 95% relative humidity) at 25 ℃ and higher intrinsic and powder dissolution rates than BCl.
CONCLUSION
The enhanced pharmaceutical properties of all three cocrystals, as compared to BCl, further contribute to the existing evidence that confirms the beneficial role of cocrystallization in facilitating drug development. These new cocrystals expand the structure landscape of BCl solid forms, which is important for future analysis to establish a reliable relationship between crystal structure and pharmaceutical properties.
Topics: Berberine; Chlorides; Crystallization; Powder Diffraction; Powders; Solubility; X-Ray Diffraction; Calorimetry, Differential Scanning
PubMed: 37226026
DOI: 10.1007/s11095-023-03533-w -
Journal of Pharmaceutical Sciences Nov 2018Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The...
Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility and wettability of both the crystalline forms were determined. It was found that surfactant can significantly improve the solubility of celastrol up to more than 10 times. Tween 80 and sodium dodecyl sulfate largely improved the wettability of the 2 crystals. Form I shows better wettability than form II in all the buffer solutions with polymers and surfactants. Compared with form II, form I exhibits higher solubility in carboxymethylcellulose and polyvinylpyrrolidone media but much lower solubility in tween 80 and sodium dodecyl sulfate solutions. An investigation of wettability and solubility mechanisms was fully explored, and a hypothesis was proposed to understand the abnormal solubility differences.
Topics: Crystallization; Crystallography, X-Ray; Models, Molecular; Pentacyclic Triterpenes; Polysorbates; Powder Diffraction; Sodium Dodecyl Sulfate; Solubility; Surface-Active Agents; Tripterygium; Triterpenes; Wettability; X-Ray Diffraction
PubMed: 30017890
DOI: 10.1016/j.xphs.2018.07.008 -
Journal of Visualized Experiments : JoVE Jan 2017In this report we describe detailed procedures for carrying out single crystal X-ray diffraction experiments with a diamond anvil cell (DAC) at the GSECARS 13-BM-C...
In this report we describe detailed procedures for carrying out single crystal X-ray diffraction experiments with a diamond anvil cell (DAC) at the GSECARS 13-BM-C beamline at the Advanced Photon Source. The DAC program at 13-BM-C is part of the Partnership for Extreme Xtallography (PX^2) project. BX-90 type DACs with conical-type diamond anvils and backing plates are recommended for these experiments. The sample chamber should be loaded with noble gas to maintain a hydrostatic pressure environment. The sample is aligned to the rotation center of the diffraction goniometer. The MARCCD area detector is calibrated with a powder diffraction pattern from LaB6. The sample diffraction peaks are analyzed with the ATREX software program, and are then indexed with the RSV software program. RSV is used to refine the UB matrix of the single crystal, and with this information and the peak prediction function, more diffraction peaks can be located. Representative single crystal diffraction data from an omphacite (Ca0.51Na0.48)(Mg0.44Al0.44Fe0.14Fe0.02)Si2O6 sample were collected. Analysis of the data gave a monoclinic lattice with P2/n space group at 0.35 GPa, and the lattice parameters were found to be: a = 9.496 ±0.006 Å, b = 8.761 ±0.004 Å, c = 5.248 ±0.001 Å, β = 105.06 ±0.03º, α = γ = 90º.
Topics: Crystallography, X-Ray; Diamond; Powder Diffraction; Pressure; Synchrotrons
PubMed: 28117811
DOI: 10.3791/54660