X-ray Diffraction of Water in Polyvinylpyrrolidone.

PVP is a hydrophilic polymer commonly used as an excipient in pharmaceutical formulations. Here we have performed time-resolved high-energy X-ray scattering experiments on pellets of PVP at different humidity conditions for 1-2 days. A two-phase exponential decay in water sorption is found with a peak in the differential pair distribution function at 2.85 Å, which is attributed to the average (hydrogen bonded) carbonyl oxygen-water oxygen distance. Additional scattering measurements on powders with fixed compositions ranging from 2 to 12.3 wt % H2O were modeled with Empirical Potential Structure Refinement (EPSR). The models reveal approximately linear relations between the carbonyl oxygen-water oxygen coordination number (nOC-OW) and the water oxygen-water oxygen coordination number (nOW-OW) versus water content in PVP. A stronger preference for water-water hydrogen bonding over carbonyl-water bonding is found. At all the concentrations studied the majority of water molecules were found to be randomly isolated, but a wide distribution of coordination environments of water molecules is found within the PVP polymer strands at the highest concentrations. Overall, the EPSR models indicate a continuous evolution in structure versus water content with nOW-OW=1 occurring at ∼12 wt % H2O, i.e., the composition where, on average, each water molecule is surrounded by one other water molecule.

The structure of molten calcium ferrite under various redox conditions.

Laser-heated melts based on the 43CaO-57Fe2O3-x eutectic, close to the calcium ferrite (CF) composition, were measured with high-energy X-ray diffraction using aerodynamic levitation over a range of redox states controlled by CO/CO2 gas atmospheres. The iron-oxygen coordination number was found to rise from 4.4 ± 0.3 at 15% Fe3+ to 5.3 ± 0.3 at 87% Fe3+. Empirical potential structure refinement modelling was used to obtain the ferric and ferrous partial pair distribution functions. It was found that the Fe2+ iron-oxygen coordination number is consistently approximately 10% higher in CF than in pure iron oxide, while Fe3+ is essentially identical in all but the most oxygen-rich environments (where it is higher in CF compared with FeOx). The model also shows calcium octahedra to be the dominant species across all redox environments, although the population of CaO7 increases with the availability of oxygen at the expense of CaO4 and CaO5. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.

Boron coordination change in barium borate melts and glasses and its contribution to configurational heat capacity, entropy, and fragility.

High-energy x-ray diffraction from molten and glassy BaB2O4 and BaB4O7 has been performed using aerodynamic levitation and laser heating over a wide range of temperatures. Remarkably, even in the presence of a heavy metal modifier dominating x-ray scattering, it was possible to extract accurate values for the tetrahedral, sp3, boron fraction, N4, which declines with increasing temperature, using bond valence-based mapping from the measured mean B-O bond lengths while accounting for vibrational thermal expansion. These are used within a boron-coordination-change model to extract enthalpies, ΔH, and entropies, ΔS, of isomerization between sp2 and sp3 boron. The results for BaB4O7, ΔH = 22(3) kJ mol-1 boron, ΔS = 19(2) J mol-1 boron K-1, agree quantitatively with those found previously for Na2B4O7. Analytical expressions for N4(J, T) and associated configurational heat capacity, CPconf(J, T), and entropy, Sconf(J, T), contributions are extended to cover a wide composition range 0 ≤ J = BaO/B2O3 ≤ 3 using a model for ΔH(J) and ΔS(J) derived empirically for lithium borates. Maxima in the CPconf(J, Tg) and fragility index contributions are thereby predicted for J ≲ 1, higher than the maximum observed and predicted in N4(J, Tg) at J ≃ 0.6. We discuss the utility of the boron-coordination-change isomerization model in the context of borate liquids containing other modifiers and the prospect of neutron diffraction to aid in empirical determinations of modifier-dependent effects, illustrated by new neutron diffraction data on Ba11B4O7 glass, its well-known α-polymorph, and lesser-known δ-phase.

Structure and Liquid Fragility in Sodium Carbonate.

The relationship between local structure and dynamics is explored for molten sodium carbonate. A flexible fluctuating-charge model, which allows for changes in the shape and charge distribution of the carbonate molecular anion, is developed. The system shows the evolution of highly temperature-dependent complex low-dimensional structures which control the dynamics (and hence the liquid fragility). By varying the molecular anion charge distribution, the key interactions responsible for the formation of these structures can be identified and rationalized. An increase in the mean charge separation within the carbonate ions increases the connectivity of the emerging structures and leads to an increase in the system fragility.

Using containerless methods to develop amorphous pharmaceuticals.

BACKGROUND: Many pipeline drugs have low solubility in their crystalline state and require compounding in special dosage forms to increase bioavailability for oral administration. The use of amorphous formulations increases solubility and uptake of active pharmaceutical ingredients. These forms are rapidly gaining commercial importance for both pre-clinical and clinical use. METHODS: Synthesis of amorphous drugs was performed using an acoustic levitation containerless processing method and spray drying. The structure of the products was investigated using in-situ high energy X-ray diffraction. Selected solvents for processing drugs were investigated using acoustic levitation. The stability of amorphous samples was measured using X-ray diffraction. Samples processed using both spray drying and containerless synthesis were compared. RESULTS: We review methods for making amorphous pharmaceuticals and present data on materials made by containerless processing and spray drying. It was shown that containerless processing using acoustic levitation can be used to make phase-pure forms of drugs that are known to be difficult to amorphize. The stability and structure of the materials was investigated in the context of developing and making clinically useful formulations. CONCLUSIONS: Amorphous compounds are emerging as an important component of drug development and for the oral delivery of drugs with low solubility. Containerless techniques can be used to efficiently synthesize small quantities of pure amorphous forms that are potentially useful in pre-clinical trials and for use in the optimization of clinical products. GENERAL SIGNIFICANCE: Developing new pharmaceutical products is an essential enterprise to improve patient outcomes. The development and application of amorphous pharmaceuticals to increase absorption is rapidly gaining importance and it provides opportunities for breakthrough research on new drugs. There is an urgent need to solve problems associated with making formulations that are both stable and that provide high bioavailability. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

The structure of liquid alkali nitrates and nitrites.

High energy X-ray diffraction has been combined with containerless techniques to determine the structure of a series of alkali and ammonium nitrate and nitrite liquids. The systems have been modelled using molecular dynamics simulation which allows for the flexibility of, and movement of charge within, the molecular anions. The model reproduces the experimentally-determined scattering functions in both the low- and high-Q regimes reflecting the inter- and intra-molecular length-scales. For ammonium nitrate the best fit to the diffraction data is obtained by assuming the NH4+ cation to have a radius closer to that for Cs+ rather than a smaller cation such as Rb+ as often previously assumed. The alkali nitrites show an emergent length scale, attributed to the nitrogen-nitrogen spatial correlations, that depends on both temperature and the identity of the alkali cation. The corresponding nitrates show a more subtle effect in the nitrogen-nitrogen correlations. As a result, the nature of this N-N length-scale appears different for the respective nitrites and nitrates.

Structure of the floating water bridge and water in an electric field.

The floating water bridge phenomenon is a freestanding rope-shaped connection of pure liquid water, formed under the influence of a high potential difference (approximately 15 kV). Several recent spectroscopic, optical, and neutron scattering studies have suggested that the origin of the bridge is associated with the formation of anisotropic chains of water molecules in the liquid. In this work, high energy X-ray diffraction experiments have been performed on a series of floating water bridges as a function of applied voltage, bridge length, and position within the bridge. The two-dimensional X-ray scattering data showed no direction-dependence, indicating that the bulk water molecules do not exhibit any significant preferred orientation along the electric field. The only structural changes observed were those due to heating, and these effects were found to be the same as for bulk water. These X-ray scattering measurements are supported by molecular dynamics (MD) simulations which were performed under electric fields of 10(6) V/m and 10(9) V/m. Directional structure factor calculations were made from these simulations parallel and perpendicular to the E-field. The 10(6) V/m model showed no significant directional-dependence (anisotropy) in the structure factors. The 10(9) V/m model however, contained molecules aligned by the E-field, and had significant structural anisotropy.

Low cation coordination in oxide melts.

The complete set of partial pair distribution functions for a rare earth oxide liquid are measured by combining aerodynamic levitation, neutron and x-ray diffraction on Y2O3, and Ho2O3 melts at 2870 K. The average Y-O (or Ho-O) coordination of these isomorphic melts is measured to be 5.5(2), which is significantly less than the octahedral coordination of crystalline Y2O3 (or Ho2O3). Investigation of La2O3, ZrO2, and Al2O3 melts by x-ray diffraction and molecular dynamics simulations also show lower-than-crystal cation-oxygen coordination. These measurements suggest a general trend towards lower coordination compared to their crystalline counterparts. It is found that the coordination drop is larger for lower field strength, larger radius cations and is negligible for high field strength (network forming) cations, such as SiO2. These findings have broad implications for predicting the local structure and related physical properties of metal-oxide melts and oxide glasses.

Relationship between topological order and glass forming ability in densely packed enstatite and forsterite composition glasses.

The atomic structures of magnesium silicate melts are key to understanding processes related to the evolution of the Earth's mantle and represent precursors to the formation of most igneous rocks. Magnesium silicate compositions also represent a major component of many glass ceramics, and depending on their composition can span the entire fragility range of glass formation. The silica rich enstatite (MgSiO(3)) composition is a good glass former, whereas the forsterite (Mg(2)SiO(4)) composition is at the limit of glass formation. Here, the structure of MgSiO(3) and Mg(2)SiO(4) composition glasses obtained from levitated liquids have been modeled using Reverse Monte Carlo fits to diffraction data and by density functional theory. A ring statistics analysis suggests that the lower glass forming ability of the Mg(2)SiO(4) glass is associated with a topologically ordered and very narrow ring distribution. The MgO(x) polyhedra have a variety of irregular shapes in MgSiO(3) and Mg(2)SiO(4) glasses and a cavity analysis demonstrates that both glasses have almost no free volume due to a large contribution from edge sharing of MgO(x)-MgO(x) polyhedra. It is found that while the atomic volume of Mg cations in the glasses increases compared to that of the crystalline phases, the number of Mg-O contacts is reduced, although the effective chemical interaction of Mg(2+) remains similar. This unusual structure-property relation of Mg(2)SiO(4) glass demonstrates that by using containerless processing it may be possible to synthesize new families of dense glasses and glass ceramics with zero porosity.

Structural changes in supercooled Al2O3-Y2O3 liquids.

Structural changes in liquids between Al2O3 and Y2O3 are investigated as a function of the composition and during supercooling using high energy X-ray diffraction (HEXRD) techniques combined with containerless aerodynamic levitation. Many-body molecular dynamics simulation techniques utilizing potential models that incorporate anion polarization effects are applied to study the same liquid systems. The X-ray scattering experiments indicate a change in liquid structure during supercooling around a composition 20% Y2O3 (AlY20) that occurs over a narrow temperature interval. We have associated this change in structure with the onset of a liquid-liquid phase transformation. Analysis of the MD simulated structures has allowed the structure changes to be interpreted in terms of Al(3+) and Y(3+) coordination environments and particularly the Y(3+)-Y(3+) structural correlations. We show that the incipient liquid-liquid phase transition behaviour is correlated with local density fluctuations that represent different coordination polyhedra surrounding oxygen ions. The difference in energy and volume associated with this sampling of high and low density basins in the underlying energy landscape is consistent with independent verifications of the volume and enthalpy differences between different amorphous forms. The differences in the high- and low-density configurations match the difference in diffraction patterns observed experimentally.

A time resolved high energy X-ray diffraction study of cooling liquid SiO2.

The evolution of the X-ray structure factor and corresponding pair distribution function of SiO2 has been measured upon cooling from the melt using high energy X-ray diffraction combined with aerodynamic levitation. Small changes in the position of the average Si-O bond distance and peak width are found to occur at ~1500(100) K in the region of the calorimetric glass transition temperature, T(g) and the observed density minima. At higher temperatures deviations from linear behavior are seen in the first sharp diffraction peak width, height and area at around 1750(50) K, which coincides with the reported density maximum around 1.2T(g).

A High Energy X-ray Diffraction Study of Amorphous Indomethacin.

Amorphous pharmaceuticals often possess a wide range of molecular conformations and bonding arrangements. The x-ray pair distribution function (PDF) method is a powerful technique for the characterization of variations in both intra-molecular and inter-molecular packing arrangements. Here, the x-ray PDF of amorphous Indomethacin is shown to be particularly sensitive to the preferred orientations of the chlorobenzyl ring found in isomers in the crystalline state. In some cases, the chlorobenzyl ring has no preferred torsional angle in the amorphous form, while in others evidence of distinct isomer orientations are observed. Amorphous samples with no preferred torsion angles of the chlorobenzyl ring are found to favor enhanced inter-molecular hydrogen bonding, and this is reflected in the intensity of the first sharp diffraction peak. These significant variations in structure rule out amorphous Indomethacin as a possible standard for x-ray PDF measurements. At high humidity, time resolved PDF's for >40 h reveal water molecules forming hydrogen bonds with Indomethacin molecules. A simple linear hydrogen bond model indicates that water molecules in the wet amorphous form have similar hydrogen bond strengths to those found between Indomethacin dimers or chains in the dry amorphous form.

Hard x-ray methods for studying the structure of amorphous thin films and bulk glassy oxides.

High-energy photon diffraction minimizes many of the corrections associated with laboratory x-ray diffractometers, and enables structure factor measurements to be made over a wide range of momentum transfers. The method edges us closer toward an ideal experiment, in which coordination numbers can be extracted without knowledge of the sample density. Three case studies are presented that demonstrate new hard x-ray methods for studying the structure of glassy and amorphous materials. First, the methodology and analysis of high-energy grazing incidence on thin films is discussed for the case of amorphous In2O3. The connectivity of irregular InO6polyhedra are shown to exist in face-, edge- and corner-shared configurations in the approximate ratio of 1:2:3. Secondly, the technique of high-energy small and wide angle scattering has been carried out on laser heated and aerodynamically levitated samples of silica-rich barium silicate (20BaO:80SiO2), from the single phase melt at 1500oC to the phase separated glass at room temperature. Based on Ba-O coordination numbers of 6 to 7, it is argued that the although the potential of Ba is ionic, it is weak enough to cause the liquid-liquid immiscibility to become metastable. Lastly, high-energy small and wide angle scattering has also been applied to high water content (up to 12 wt.%) samples of hydrous SiO2glass quenched from 1500oC at 4 GPa. An increase of Si1-O2correlations at 4.3 Å is found to be consistent with an increase in the population of three-membered SiO4rings at the expense of larger rings.

Corium lavas: structure and properties of molten UO2-ZrO2 under meltdown conditions.

In the exceedingly rare event of nuclear reactor core meltdown, uranium dioxide fuel reacts with Zircaloy cladding to produce eutectic melts which can subsequently be oxidized by coolant/moderator water. Oxidized corium liquids in the xUO2·(100 - x)ZrO2 system were produced via laser melting of UO2-ZrO2 mixtures to temperatures in excess of 3000 K. Contamination was avoided by floating the droplets on a gas stream within an aerodynamic levitator and in-situ high-energy x-ray diffraction experiments allowed structural details to be elucidated. Molecular dynamics simulations well reproduced diffraction and density data, and show less compositional variation in thermal expansion and viscosity than suggested by existing measurements. As such, corium liquids maintain their highly penetrating nature irrespective of the amount of oxidized cladding dissolved in the molten fuel. Metal-oxygen coordination numbers vary with both composition and temperature. The former is due to mismatch in native values, nUO(x = 100) ≈ 7 and nZrO(x = 0) ≈ 6, and the requirement for oxygen site stabilization. The latter provides a thermal expansion mechanism.

Automated sample exchange and tracking system for neutron research at cryogenic temperatures.

An automated system for sample exchange and tracking in a cryogenic environment and under remote computer control was developed. Up to 24 sample "cans" per cycle can be inserted and retrieved in a programed sequence. A video camera acquires a unique identification marked on the sample can to provide a record of the sequence. All operations are coordinated via a LABVIEW program that can be operated locally or over a network. The samples are contained in vanadium cans of 6-10 mm in diameter and equipped with a hermetically sealed lid that interfaces with the sample handler. The system uses a closed-cycle refrigerator (CCR) for cooling. The sample was delivered to a precooling location that was at a temperature of approximately 25 K, after several minutes, it was moved onto a "landing pad" at approximately 10 K that locates the sample in the probe beam. After the sample was released onto the landing pad, the sample handler was retracted. Reading the sample identification and the exchange operation takes approximately 2 min. The time to cool the sample from ambient temperature to approximately 10 K was approximately 7 min including precooling time. The cooling time increases to approximately 12 min if precooling is not used. Small differences in cooling rate were observed between sample materials and for different sample can sizes. Filling the sample well and the sample can with low pressure helium is essential to provide heat transfer and to achieve useful cooling rates. A resistive heating coil can be used to offset the refrigeration so that temperatures up to approximately 350 K can be accessed and controlled using a proportional-integral-derivative control loop. The time for the landing pad to cool to approximately 10 K after it has been heated to approximately 240 K was approximately 20 min.

Topological ordering in liquid UO2.

A molecular dynamics model of liquid UO2 that is in good agreement with recent high-energy x-ray diffraction data has been analyzed using the Bhatia-Thornton formalism. A pre-peak appears in the topological structure factor S NN(Q) at Q = 1.85(1)Å(-1) which is not present in the more common, element specific Faber-Ziman partial structure factors. A radical Voronoi tessellation of the 3D molecular dynamics model shows the presence of a wide distribution of clusters, consistent with presence of highly mobile oxygen atoms. However, 4-fold Voronoi polyhedra (n 4) are found to dominate the structure and the majority of clusters can be described by the distribution n 3 ⩽ n 4 ⩾ n 5. It is argued that an open network of 4-fold Voronoi polyhedra could explain the origin of the pre-peak in S NN(Q) and the topological ordering observed in liquid UO2.

Aerodynamic levitator for in situ x-ray structure measurements on high temperature and molten nuclear fuel materials.

An aerodynamic levitator with carbon dioxide laser beam heating was integrated with a hermetically sealed controlled atmosphere chamber and sample handling mechanism. The system enabled containment of radioactive samples and control of the process atmosphere chemistry. The chamber was typically operated at a pressure of approximately 0.9 bars to ensure containment of the materials being processed. Samples 2.5-3 mm in diameter were levitated in flowing gas to achieve containerless conditions. Levitated samples were heated to temperatures of up to 3500 °C with a partially focused carbon dioxide laser beam. Sample temperature was measured using an optical pyrometer. The sample environment was integrated with a high energy (100 keV) x-ray synchrotron beamline to enable in situ structure measurements to be made on levitated samples as they were heated, melted, and supercooled. The system was controlled from outside the x-ray beamline hutch by using a LabVIEW program. Measurements have been made on hot solid and molten uranium dioxide and binary uranium dioxide-zirconium dioxide compositions.

Low-Dimensional Network Formation in Molten Sodium Carbonate.

Molten carbonates are highly inviscid liquids characterized by low melting points and high solubility of rare earth elements and volatile molecules. An understanding of the structure and related properties of these intriguing liquids has been limited to date. We report the results of a study of molten sodium carbonate (Na2CO3) which combines high energy X-ray diffraction, containerless techniques and computer simulation to provide insight into the liquid structure. Total structure factors (F(x)(Q)) are collected on the laser-heated carbonate spheres suspended in flowing gases of varying composition in an aerodynamic levitation furnace. The respective partial structure factor contributions to F(x)(Q) are obtained by performing molecular dynamics simulations treating the carbonate anions as flexible entities. The carbonate liquid structure is found to be heavily temperature-dependent. At low temperatures a low-dimensional carbonate chain network forms, at T = 1100 K for example ~55% of the C atoms form part of a chain. The mean chain lengths decrease as temperature is increased and as the chains become shorter the rotation of the carbonate anions becomes more rapid enhancing the diffusion of Na(+) ions.

Liquid B2O3 up to 1700 K: x-ray diffraction and boroxol ring dissolution.

Using high energy x-ray diffraction, the structure factors of glassy and molten B2O3 were measured with high signal-to-noise, up to a temperature of T = 1710(20) K. The observed systematic changes with T are shown to be consistent with the dissolution of hexagonal [B3O6] boroxol rings, which are abundant in the glass, whilst the high-T (>~1500 K) liquid can be more closely described as a random network structure based on [BO3] triangular building blocks. We therefore argue that diffraction data are in fact qualitatively sensitive to the presence of small rings, and support the existence of a continuous structural transition in molten B2O3, for which the temperature evolution of the 808 cm−1 Raman scattering band (boroxol breathing mode) has long stood as the most emphatic evidence. Our conclusions are supported by both first-principles and polarizable ion model molecular dynamics simulations which are capable of giving good account of the experimental data, so long as steps are taken to ensure a ring fraction similar to that expected from Raman spectroscopy. The mean thermal expansion of the B-O bond has been measured directly to be αBO = 3.7(2) × 10−6 K−1, which accounts for a few percent of the bulk expansion just above the glass transition temperature, but accounts for greater than one third of the bulk expansion at temperatures in excess of 1673 K.