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Journal of Pharmaceutical Sciences Aug 2018Crystal structure determination from powder diffraction data (SDPD) using the DASH software package is evaluated for data recorded using transmission capillary,...
Crystal structure determination from powder diffraction data (SDPD) using the DASH software package is evaluated for data recorded using transmission capillary, transmission flat plate, and reflection flat plate geometries on a selection of pharmaceutical compounds. We show that transmission capillary geometry remains the best option when crystal structure determination is the primary consideration and, as expected, reflection flat plate geometry is not recommended for SDPD because of preferred orientation effects. However, the quality of crystal structures obtained from transmission plate instruments can be excellent, and the convenience factor for sample preparation, throughput, and retrieval is higher than that of transmission capillary instruments. Indeed, it is possible to solve crystal structures within an hour of a polycrystalline sample arriving in the laboratory, which has clear implications for making small-molecule crystal structures more routinely available to the practicing laboratory medicinal chemist. With appropriate modifications to crystal structure determination software, it can be imagined that SDPD could become a rapid turn-around walk-up analytical service in high-throughput chemical environments.
Topics: Adrenergic beta-Antagonists; Anti-Bacterial Agents; Carvedilol; Cefadroxil; Crystallography, X-Ray; Models, Molecular; Pharmaceutical Preparations; Powder Diffraction; Software; X-Ray Diffraction
PubMed: 29679705
DOI: 10.1016/j.xphs.2018.04.010 -
European Journal of Pharmaceutical... Dec 2016The aim of this work was an investigation of the physical changes of the amorphous model material spray-dried trehalose through the use of various analytical techniques...
The aim of this work was an investigation of the physical changes of the amorphous model material spray-dried trehalose through the use of various analytical techniques and to identify a suitable, rapid method able to quantify the changes. The crystallinity changes and recrystallization process of amorphous samples were investigated by hot-humidity stage X-ray powder diffractometry (HH-XRPD) with fresh samples, conventional X-ray powder diffractometry (XRPD) used stored samples and by differential scanning calorimetry (DSC). The data from the three methods were compared and the various forms of trehalose were analysed. HH-XRPD demonstrated that the recrystallization began at 40 and 60°C up to 45% RH and at 70°C up to 30% RH into dihydrate form. At 70°C up to 60% RH the anhydrous form of trehalose appeared too. Conventional XRPD results showed, that in the 28days stored samples the dihydrate form was detected at 40°C, 50% RH. Storage at 60°C, 40% RH resulted in the appearance of the anhydrous form and at 60°C, 50% RH both polymorphic forms were detected. By carrying out the DSC measurements at different temperatures the fraction of recrystallized trehalose dihydrate was detected. The recrystallization investigated by HH-XRPD and DSC followed Avrami kinetics, the calculated rate constants of isothermal crystallization (K) were same. Both HH-XRPD and conventional XRPD was suitable for the detection of the physical changes of the amorphous model material. DSC measurements showed similar results as HH-XRPD. Primarily HH-XRPD could be suggested for prediction, because the method is fast and every changes could be studied on one sample.
Topics: Crystallization; Hot Temperature; Humidity; Powder Diffraction; Trehalose; X-Ray Diffraction
PubMed: 27496047
DOI: 10.1016/j.ejps.2016.08.003 -
Journal of Pharmaceutical Sciences Dec 2017We report the effects of dry mechanochemical synthesis conditions on the crystallization of caffeine (CA) and oxalic acid (OX) 2:1 cocrystal. CA anhydrate and OX...
We report the effects of dry mechanochemical synthesis conditions on the crystallization of caffeine (CA) and oxalic acid (OX) 2:1 cocrystal. CA anhydrate and OX dihydrate were grinded at various temperatures, rotation speeds, and grinding time. The cocrystal was also synthesized by an organic solvent evaporation method, as a reference. The produced samples were measured by a powder X-ray diffraction (PXRD) analysis. The PXRD spectra suggest that the grinded cocrystal has a lower crystallinity than the evaporated one. The diffractograms for the cocrystals synthesized by 2 kinds of methods were further evaluated by multivariate curve resolution-alternating least squares method. Sources of the mathematical models constructed were assigned to the cocrystal and unreacted mixture of CA and OX dihydrate. The present approach is concluded to be useful for the improvement of pharmaceutical property because cocrystallization is closely relating to the solubility characteristics, bioavailability, stability, and so on of drugs.
Topics: Caffeine; Crystallization; Oxalic Acid; Powder Diffraction; Powders; Solubility; Solvents; Spectroscopy, Fourier Transform Infrared; Temperature; X-Ray Diffraction
PubMed: 28797789
DOI: 10.1016/j.xphs.2017.07.025 -
Journal of Pharmaceutical and... Sep 2010Two polymorphic forms of benfluorex hydrochloride, phases I and II, were isolated as monophasic polycrystalline samples, and structurally characterized using ab initio...
Two polymorphic forms of benfluorex hydrochloride, phases I and II, were isolated as monophasic polycrystalline samples, and structurally characterized using ab initio X-ray powder diffraction methods and a global optimization strategy (simulated annealing). Form I crystallizes in monoclinic system, space group P2(1)/n, with Z=4, a=21.0719(10)A, b=7.0563(4)A, c=14.8684(7)A, beta=116.998(3) degrees , V=1969.8(2)A(3), while Form II crystallizes in the orthorhombic space group Pbca, with Z=8, a=33.8031(2)A, b=15.1451(8)A, c=7.6138(6)A, V=3897.9(4)A(3). Crystals of Form I and Form II of benfluorex hydrochloride are based upon an ionic packing of protonated benfluorex molecules at the most basic site, the N1 atoms, and chloride anions. Form I shows the presence of mu-Cl ions, generating centrosymmetric dimers with a N(2)Cl(2) moiety, while Form II contains antiparallel chains of C-H...O hydrogen-bonded molecules running along c axis. DSC and thermodiffractometric measurements showed that heating progressively Form II from ambient temperature to 160 degrees C causes a phase transition to the thermodynamically stable Form I, immediately followed by the sample melting, near 165 degrees C. Recrystallization directly to Form I is observed when the melt is cooled back to ambient temperature, with a significant hysteresis (this event being centered near 130 degrees C).
Topics: Chemistry, Pharmaceutical; Crystallization; Differential Thermal Analysis; Drug Stability; Fenfluramine; Models, Molecular; Molecular Structure; Phase Transition; Powder Diffraction; X-Ray Diffraction
PubMed: 20347245
DOI: 10.1016/j.jpba.2010.02.037 -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2003X-ray powder diffraction (XRD) data for six pure fluoroquinolone antibiotic drugs, ciprofloxacin, norfloxacin, enrofloxacin, ofloxacin, pefloxacin and sparfloxacin have...
X-ray powder diffraction (XRD) data for six pure fluoroquinolone antibiotic drugs, ciprofloxacin, norfloxacin, enrofloxacin, ofloxacin, pefloxacin and sparfloxacin have been obtained using a powder diffractometer. The drugs were scanned from a Bragg angle (2theta) of 10 degrees to 70 degrees. The obtained data were tabulated in terms of the lattice spacing (A) and relative line intensities (I/I(I)). This new information may be useful for the identification of these drugs.
Topics: Anti-Infective Agents; Fluoroquinolones; Molecular Structure; Powder Diffraction; X-Ray Diffraction
PubMed: 14769236
DOI: No ID Found -
Journal of Pharmaceutical Sciences Nov 2012High-throughput crystallisation and characterisation platforms provide an efficient means to carry out solid-form screening during the pre-formulation phase. To...
High-throughput crystallisation and characterisation platforms provide an efficient means to carry out solid-form screening during the pre-formulation phase. To determine the crystal structures of identified new solid phases, however, usually requires independent crystallisation trials to produce single crystals or bulk samples of sufficient quantity to carry out high-quality X-ray diffraction measurements. This process could be made more efficient by a robust procedure for crystal structure determination directly from high-throughput X-ray powder diffraction (XRPD) data. Quantum-chemical calculations based on dispersion-corrected density functional theory (DFT-D) have now become feasible for typical small organic molecules used as active pharmaceutical ingredients. We demonstrate how these calculations can be applied to complement high-throughput XRPD data by determining the crystal structure of piroxicam form III. These combined experimental/quantum-chemical methods can provide access to reliable structural information in the course of an intensive experimentally based solid-form screening activity or in other circumstances wherein single crystals might never be viable, for example, for polymorphs obtained only during high-energy processing such as spray drying or milling.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Molecular Structure; Piroxicam; Powder Diffraction; Quantum Theory
PubMed: 22886472
DOI: 10.1002/jps.23287 -
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 -
Acta Crystallographica. Section C,... Feb 2012The structure of the metastable form I polymorph of the macrolide antibiotic clarithromycin, C(38)H(69)NO(13), was determined by a powder diffraction method using...
The structure of the metastable form I polymorph of the macrolide antibiotic clarithromycin, C(38)H(69)NO(13), was determined by a powder diffraction method using synchrotron radiation. The space group of form I is P2(1)2(1)2. The initial model was determined by a molecular replacement method using the structure of clarithromycin form 0 as a search model, and the final structure was obtained through Rietveld refinements. In the form I crystal structure, the clarithromycin molecules are aligned parallel along the a axis in a head-to-tail manner with intermolecular hydrogen bonds between the hydroxy O atoms. The dimethylamine groups of the clarithromycin molecule interdigitate between neighbouring head-to-tail clarithromycin alignments. The novel crystal packing found in form I provides a mechanism that describes the transformation of form 0 to form I.
Topics: Clarithromycin; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Powder Diffraction; Synchrotrons; X-Ray Diffraction
PubMed: 22307251
DOI: 10.1107/S0108270111054230 -
Pharmaceutical Research Jan 2013To clarify the polymorphism of racemic Ibuprofen and to determine the kinetic of the phase transformation that follows crystallisation of phase II.
PURPOSE
To clarify the polymorphism of racemic Ibuprofen and to determine the kinetic of the phase transformation that follows crystallisation of phase II.
METHODS
Differential Scanning Calorimetry (DSC), X-ray powder diffraction and Hot Stage Microscopy are complementarily used to perform a kinetic investigation of the particular temperature range where competition between the occurrence of phases I and II is suspected.
RESULTS
Experiments performed with the three techniques reveal that at 273 K the crystallisation to phase II is then followed by a solid-solid transition towards phase I. This transformation is exothermic (conversion enthalpy of 8.0 ± 0.5 kJ/mol), which proves that the two phases form a monotropic set. The kinetics of conversion deduced from X-Ray experiments follows a Johnson-Mehl-Avrami equation and the Hot Stage Microscopy allows us to establish that the transformation proceeds by the growth of some nuclei of phase I probably formed at lower temperature.
CONCLUSIONS
These results allow us to precise the stability pattern of racemic Ibuprofen and to establish the kinetic conditions of appearance and interconversion of the different phases. Therefore such real time resolved investigations would help if applied in the screening of polymorphs when competitive crystallisations occur.
Topics: Analgesics, Non-Narcotic; Calorimetry, Differential Scanning; Crystallization; Ibuprofen; Kinetics; Phase Transition; Powder Diffraction; X-Ray Diffraction
PubMed: 22878684
DOI: 10.1007/s11095-012-0851-0 -
Journal of Pharmaceutical Sciences Sep 2014Structural investigations of a nonstoichiometric hydrate, AMG 222 tosylate, a DPP-IV inhibitor in clinical development for type II diabetes, were performed using a...
Structural studies of a non-stoichiometric channel hydrate using high resolution X-ray powder diffraction, solid-state nuclear magnetic resonance, and moisture sorption methods.
Structural investigations of a nonstoichiometric hydrate, AMG 222 tosylate, a DPP-IV inhibitor in clinical development for type II diabetes, were performed using a multitechnique approach. The moisture sorption isotherm is in good agreement with a simple Langmuir model, suggesting that the hydrate water is located in well-defined crystallographic sites, which become vacant during dehydration. Crystal structures of AMG 222 tosylate at ambient and dry conditions were determined from high-resolution X-ray diffraction using the direct space method. On the basis of these crystal structures, hydrated water is located in channels formed by the drug framework. Upon dehydration, an isostructural dehydrate is formed with the channels remaining void and accessible to water for rehydration. Kitaigorodskii packing coefficients of the solid between relative humidity of 0% and 90% indicate that the equilibrium form of AMG 222 tosylate is the fully hydrated monohydrate.
Topics: Crystallization; Dehydration; Dibenzocycloheptenes; Drug Stability; Humidity; Magnetic Resonance Spectroscopy; Powder Diffraction; Powders; Tetrazoles; Water; X-Ray Diffraction
PubMed: 24470123
DOI: 10.1002/jps.23873