scholarly journals Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 342 ◽  
Author(s):  
Hannes Lengauer ◽  
Damjan Makuc ◽  
Damjan Šterk ◽  
Franc Perdih ◽  
Arthur Pichler ◽  
...  
Keyword(s):  
Solid State ◽  
Scientific Literature ◽  
Crystal Form ◽  
X Ray Diffraction ◽  
Ionization State ◽  
Crystal Forms ◽  
X Ray ◽  
Drug Products ◽  
Pure Salt ◽  
Tenofovir Alafenamide

Tenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no data in the scientific literature on the solid state properties of TAF. In our report, we describe the preparation of two novel polymorphs II and III of tenofovir alafenamide monofumarate (TA MF2 and TA MF3). The solid-state structure of these compounds was investigated in parallel to the previously known tenofovir alafenamide monofumarate form I (TA MF1) and tenofovir alafenamide hemifumarate (TA HF). Interestingly, the single-crystal X-ray diffraction of TA HF revealed that this derivative exists as a co-crystal form. In addition, we prepared a crystalline tenofovir alafenamide free base (TA) and its hydrochloride salt (TA HCl), which enabled us to determine the structure of TA MF derivatives using 15N-ssNMR (15N-solid state nuclear magnetic resonance). Surprisingly, we observed that TA MF1 exists as a mixed ionization state complex or pure salt, while TA MF2 and TA MF3 can be obtained as pure co-crystal forms.

scholarly journals Born out of Fire and Ice: Polymorph Studies of the Antiviral Famciclovir

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 129
Author(s):  
Liana Vella-Zarb ◽  
Ulrich Baisch
Keyword(s):  
Variable Temperature ◽  
Chemical Properties ◽  
Crystal Form ◽  
X Ray Diffraction ◽  
Crystal Forms ◽  
X Ray ◽  
Physical Chemical ◽  
Diffraction Patterns ◽  
Crystalline Forms

There is much interest and focus on solid forms of famciclovir. However, in spite of the abundance of reported differences in oral bioavailability, compressibility, and other physical–chemical properties of the various crystal forms of this drug, very little precise structural analysis is available in the literature to date. The form used in the commercial formulation is the anhydrous form I. Patents and patent applications report three different anhydrous crystalline forms on the basis of unindexed powder diffraction patterns. Single-crystal and variable-temperature X-ray diffraction experiments using the commercially available anhydrous form of famciclovir were carried out and led not only to the crystal structure determination of the anhydrous form I, but also to discovery of a new crystal form of anhydrous famciclovir from powder data.

Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid

2019 ◽  
Vol 75 (6) ◽  
pp. 793-805
Author(s):  
Dorota Pogoda ◽  
Jan Janczak ◽  
Sylwia Pawlak ◽  
Michael Zaworotko ◽  
Veneta Videnova-Adrabinska
Keyword(s):  
Solid State ◽  
Kynurenic Acid ◽  
Variable Temperature ◽  
Neurological Diseases ◽  
Crystal Form ◽  
Phase Behaviour ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray

Kynurenic acid (KYN; systematic name: 4-hydroxyquinoline-2-carboxylic acid, C10H7NO3) displays a therapeutic effect in the treatment of some neurological diseases and is used as a broad-spectrum neuroprotective agent. However, it is understudied with respect to its solid-state chemistry and only one crystal form (α-KYN·H2O) has been reported up to now. Therefore, an attempt to synthesize alternative solid-state forms of KYN was undertaken and six new species were obtained: five solvates and one salt. One of them is a new polymorph, β-KYN·H2O, of the already known KYN monohydrate. All crystal species were further studied by single-crystal and powder X-ray diffraction, thermal and spectroscopic methods. In addition to the above methods, differential scanning calorimetry (DSC), in-situ variable-temperature powder X-ray diffraction and Raman microscopy were applied to characterize the phase behaviour of the new forms. All the compounds display a zwitterionic form of KYN and two different enol–keto tautomers are observed depending on the crystallization solvent used.

Polyethersulfone polymers and oligomers — Morphology and crystallization

2012 ◽  
Vol 90 (10) ◽  
pp. 880-890 ◽  
Author(s):  
Abdelkader Benhalima ◽  
François Hudon ◽  
Finda Koulibaly ◽  
Christian Tessier ◽  
Josée Brisson
Keyword(s):  
Molecular Weight ◽  
Model Compound ◽  
Crystal Form ◽  
Low Molecular Weight ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
Crystal Forms ◽  
X Ray ◽  
Diphenyl Sulfone ◽  
Induced Crystallization

Crystal forms of polyethersulfones (PES) were investigated by using a model compound and a low molecular weight oligomer. These are amorphous as-synthesized, and can undergo solvent-induced crystallization under the appropriate conditions. The model compound, 4,4′-bis(p-methoxyphenoxy)diphenyl sulfone, yielded monocrystals, and its structure was solved using X-ray diffraction. Conformational disorder is present, two conformers cohabiting in 55:45 proportions. This model compound, combined to previous structural studies published in the literature, served as a basis for conformational studies of polyethersulfone. Low molecular weight polymers submitted to solvent-induced crystallization resulted in a PES crystal form different from that previously published in the literature, as shown by powder X-ray diffraction.

A time-resolved SAXS study on the crystalline morphology of long-term stored isotactic polypropylene

2004 ◽  
Vol 37 (2) ◽  
pp. 295-299 ◽  
Author(s):  
Jun-Ting Xu ◽  
Yu-Jin Zhang ◽  
Zhi-Qiang Fan
Keyword(s):  
Isotactic Polypropylene ◽  
Crystal Form ◽  
Crystalline Morphology ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Time Resolved ◽  
Crystal Forms ◽  
X Ray ◽  
X Ray Scattering

The crystalline morphology of a long-term stored metallocene isotactic polypropylene (mPP) has been studied with time-resolved small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD), and compared with that of the freshly crystallized sample. It was found that both α and γ crystal forms occur in the long-term stored mPP, whereas freshly crystallized mPP contains only the α crystal form. Double SAXS peaks were observed for the long-term stored mPP, which can be assigned to the α and γ crystals. Based on the SAXS result, it is inferred that the crystal stacks of the α and γ forms in the long-term stored mPP are arranged according to the block mode.

The Collagenic Molecular Structural Unit of Solid State Complexes

1971 ◽  
Vol 29 ◽  
pp. 478-479
Author(s):  
Kenneth M. Richter ◽  
John A. Schilling
Keyword(s):  
Molecular Weight ◽  
Solid State ◽  
Structural Unit ◽  
X Ray Diffraction ◽  
X Ray ◽  
Naoh Treatment

The structural unit of solid state collagen complexes has been reported by Porter and Vanamee via EM and by Cowan, North and Randall via x-ray diffraction to be an ellipsoidal unit of 210-270 A. length by 50-100 A. diameter. It subsequently was independently demonstrated by us in dog tendon, dermis, and induced complexes. Its detailed morphologic, dimensional and molecular weight (MW) aspects have now been determined. It is pear-shaped in long profile with m diameters of 57 and 108 A. and m length of 263 A. (Fig. 1, tendon, KMnO4 fixation, Na-tungstate; Fig. 2a, schematic of unit in long, C, and x-sectional profiles of its thin, xB, and bulbous, xA portions; Fig. 2b, tendon essentially unmodified by ether and 0.4 N NaOH treatment, Na-tungstate). The unit consists of a uniquely coild cable, c, of ṁ 22.9 A. diameter and length of 2580-3316 A. The cable consists of three 2nd-strands, s, each of m 10.6 A.

TEM studies of solid-state reactions in sputter-deposited Nb/Al multilayer thin films

1996 ◽  
Vol 54 ◽  
pp. 1020-1021
Author(s):  
F. Ma ◽  
S. Vivekanand ◽  
K. Barmak ◽  
C. Michaelsen
Keyword(s):  
Thin Films ◽  
Solid State ◽  
Stoichiometric Composition ◽  
Analytical Electron Microscopy ◽  
Grain Structure ◽  
Solid State Reactions ◽  
Multilayer Thin Films ◽  
X Ray Diffraction ◽  
X Ray ◽  
Sputter Deposited

Solid state reactions in sputter-deposited Nb/Al multilayer thin films have been studied by transmission and analytical electron microscopy (TEM/AEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The Nb/Al multilayer thin films for TEM studies were sputter-deposited on (1102)sapphire substrates. The periodicity of the films is in the range 10-500 nm. The overall composition of the films are 1/3, 2/1, and 3/1 Nb/Al, corresponding to the stoichiometric composition of the three intermetallic phases in this system.Figure 1 is a TEM micrograph of an as-deposited film with periodicity A = dA1 + dNb = 72 nm, where d's are layer thicknesses. The polycrystalline nature of the Al and Nb layers with their columnar grain structure is evident in the figure. Both Nb and Al layers exhibit crystallographic texture, with the electron diffraction pattern for this film showing stronger diffraction spots in the direction normal to the multilayer. The X-ray diffraction patterns of all films are dominated by the Al(l 11) and Nb(l 10) peaks and show a merging of these two peaks with decreasing periodicity.

Fabrication and study the effect of the laser on the properties of the compound Tl2-xHgxBa2-ySryCa2Cu3O10+δ superconductor

2018 ◽  
pp. 168
Author(s):  
A. Kareem Dahash Ali ◽  
Nihad Ali Shafeek
Keyword(s):  
Transition Temperature ◽  
Solid State ◽  
Hydrostatic Pressure ◽  
Electrical Properties ◽  
Co2 Laser ◽  
Temperature Shift ◽  
Unit Cell ◽  
X Ray Diffraction ◽  
X Ray ◽  
Structural And Electrical Properties

This study included the fabrication of    compound (Tl2-xHgxBa2-ySryCa2Cu3O10+δ) in a manner solid state and under hydrostatic pressure ( 8 ton/cm2) and temperature annealing(850°C), and determine the effect of the laser on the structural and electrical properties elements in the compound, and various concentrations of x where (x= 0.1,0.2,0.3 ). Observed by testing the XRD The best ratio of compensation for x is 0.2 as the value of a = b = 5.3899 (A °), c = 36.21 (A °) show that the installation of four-wheel-based type and that the best temperature shift is TC= 142 K  .When you shine a CO2 laser on the models in order to recognize the effect of the laser on these models showed the study of X-ray diffraction of these samples when preparing models with different concentrations of the values ​​of x, the best ratio of compensation is 0.2 which showed an increase in the values ​​of the dimensions of the unit cell a=b = 5.3929 (A °), c = 36.238 (A°). And the best transition temperature after shedding laser is TC=144 K. 

New Copper Compounds with Antiplatelet Aggregation Activity

2019 ◽  
Vol 15 (8) ◽  
pp. 850-862
Author(s):  
Mirthala Flores-García ◽  
Juan Manuel Fernández-G. ◽  
Cristina Busqueta-Griera ◽  
Elizabeth Gómez ◽  
Simón Hernández-Ortega ◽  
...  
Keyword(s):  
Schiff Base ◽  
Solid State ◽  
Thrombotic Event ◽  
X Ray Diffraction ◽  
Nmr Studies ◽  
Schiff Base Ligands ◽  
X Ray ◽  
Antiplatelet Aggregation ◽  
Aggregation Activity ◽  
L1 And L2

Background: Ischemic heart disease, cerebrovascular accident, and venous thromboembolism have the presence of a thrombotic event in common and represent the most common causes of death within the population. Objective: Since Schiff base copper(II) complexes are able to interact with polyphosphates (PolyP), a procoagulant and potentially prothrombotic platelet agent, we investigated the antiplatelet aggregating properties of two novel tridentate Schiff base ligands and their corresponding copper( II) complexes. Methods: The Schiff base ligands (L1) and (L2), as well as their corresponding copper(II) complexes (C1) and (C2), were synthesized and characterized by chemical analysis, X-ray diffraction, mass spectrometry, and UV-Visible, IR and far IR spectroscopy. In addition, EPR studies were carried out for (C1) and (C2), while (L1) and (L2) were further analyzed by 1H and 13C NMR. Tests for antiplatelet aggregation activities of all of the four compounds were conducted. Results: X-ray diffraction studies show that (L1) and (L2) exist in the enol-imine tautomeric form with a strong intramolecular hydrogen bond. NMR studies show that both ligands are found as enol-imine tautomers in CDCl3 solution. In the solid state, the geometry around the copper(II) ion in both (C1) and (C2) is square planar. EPR spectra suggest that the geometry of the complexes is similar to that observed in the solid state by X-ray crystallography. Compound (C2) exhibited the strongest antiplatelet aggregation activity. Conclusion: Schiff base copper(II) complexes, which are attracting increasing interest, could represent a new approach to treat thrombosis by blocking the activity of PolyP with a potential anticoagulant activity and, most importantly, demonstrating no adverse bleeding events.

Crystal Forms of Semisynthetic Ergot Alkaloid Terguride

2002 ◽  
Vol 67 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Michal Hušák ◽  
Bohumil Kratochvíl ◽  
Ivana Císařová ◽  
Ladislav Cvak ◽  
Alexandr Jegorov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ergot Alkaloid ◽  
Simplified Model ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
X Ray Diffraction ◽  
Torsion Angles ◽  
Crystal Forms ◽  
X Ray ◽  
Independent Molecules

Two new structures of semisynthetic ergot alkaloid terguride created by unusual number of symmetry-independent molecules were determined by X-ray diffraction methods at 150 K. Form A (monoclinic, P212121, Z = 12) contains three symmetry-independent terguride molecules and two molecules of water in the asymmetric part of the unit cell. The form CA (monoclinic, P21, Z = 8) is an anhydrate remarkable by the presence of four symmetry-independent molecules in the crystal structure. Conformations of twelve symmetry-independent molecules that were found in four already described terguride structures are compared with torsion angles obtained by ab initio quantum-mechanical calculations for the simplified model of N-cyclohexyl-N'-diethylurea.

scholarly journals Synthesis and Na+ Ion Conductivity of Stoichiometric Na3Zr2Si2PO12 by Liquid-Phase Sintering with NaPO3 Glass

Materials ◽  
2021 ◽  
Vol 14 (14) ◽  
pp. 3790
Author(s):  
Yongzheng Ji ◽  
Tsuyoshi Honma ◽  
Takayuki Komatsu
Keyword(s):  
Solid State ◽  
Liquid Phase ◽  
Sintering Temperature ◽  
Liquid Phase Sintering ◽  
Ion Conductivity ◽  
X Ray Diffraction ◽  
Conventional Solid State Reaction ◽  
X Ray ◽  
Sintering Time ◽  
Lower Activation

Sodium super ionic conductor (NASICON)-type Na3Zr2Si2PO12 (NZSP) with the advantages of the high ionic conductivity, stability and safety is one of the most famous solid-state electrolytes. NZSP, however, requires the high sintering temperature about 1200 °C and long sintering time in the conventional solid-state reaction (SSR) method. In this study, the liquid-phase sintering (LPS) method was applied to synthesize NZSP with the use of NaPO3 glass with a low glass transition temperature of 292 °C. The formation of NZSP was confirmed by X-ray diffraction analyses in the samples obtained by the LPS method for the mixture of Na2ZrSi2O7, ZrO2, and NaPO3 glass. The sample sintered at 1000 °C for 10 h exhibited a higher Na+ ion conductivity of 1.81 mS/cm at 100 °C and a lower activation energy of 0.18 eV compared with the samples prepared by the SSR method. It is proposed that a new LPE method is effective for the synthesis of NZSP and the NaPO3 glass has a great contribution to the Na+ diffusion at the grain boundaries.

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