Characterization of Pharmaceutical Tablets by X-ray Tomography

Solid dosage forms such as tablets are extensively used in drug administration for their simplicity and large-scale manufacturing capabilities. High-resolution X-ray tomography is one of the most valuable non-destructive techniques to investigate the internal structure of the tablets for drug product development as well as for a cost effective production process. In this work, we review the recent developments in high-resolution X-ray microtomography and its application towards different tablet characterizations. The increased availability of powerful laboratory instrumentation, as well as the advent of high brilliance and coherent 3rd generation synchrotron light sources, combined with advanced data processing techniques, are driving the application of X-ray microtomography forward as an indispensable tool in the pharmaceutical industry

Characterization of Open-Cell Sponges via Magnetic Resonance and X-ray Tomography

The applications of polymeric sponges are varied, ranging from cleaning and filtration to medical applications. The specific properties of polymeric foams, such as pore size and connectivity, are dependent on their constituent materials and production methods. Nuclear magnetic resonance imaging (MRI) and X-ray micro-computed tomography (mu CT) offer complementary information about the structure and properties of porous media. In this study, we employed MRI, in combination with mu CT, to characterize the structure of polymeric open-cell foam, and to determine how it changes upon compression, mu CT was used to identify the morphology of the pores within sponge plugs, extracted from polyurethane open-cell sponges. MRI T-2 relaxation maps and bulk T-2 relaxation times measurements were performed for 7 degrees dH water contained within the same polyurethane foams used for mu CT. Magnetic resonance and mu CT measurements were conducted on both uncompressed and 60% compressed sponge plugs. Compression was achieved using a graduated sample holder with plunger. A relationship between the average T-2 relaxation time and maximum opening was observed, where smaller maximum openings were found to have a shorter T-2 relaxation times. It was also found that upon compression, the average maximum opening of pores decreased. Average pore size ranges of 375-632 +/- 1 mu m, for uncompressed plugs, and 301-473 +/- 1 mu m, for compressed plugs, were observed. By determining maximum opening values and T-2 relaxation times, it was observed that the pore structure varies between sponges within the same production batch, as well as even with a single sponge

Exploration of the X-ray Dark-Field Signal in Mineral Building Materials

Mineral building materials suffer from weathering processes such as salt efflorescence, freeze–thaw cycling, and microbial colonization. All of these processes are linked to water (liquid and vapor) in the pore space. The degree of damage following these processes is heavily influenced by pore space properties such as porosity, pore size distribution, and pore connectivity. X-ray computed micro-tomography (µCT) has proven to be a valuable tool to non-destructively investigate the pore space of stone samples in 3D. However, a trade-off between the resolution and field-of-view often impedes reliable conclusions on the material’s properties. X-ray dark-field imaging (DFI) is based on the scattering of X-rays by sub-voxel-sized features, and as such, provides information on the sample complementary to that obtained using conventional µCT. In this manuscript, we apply X-ray dark-field tomography for the first time on four mineral building materials (quartzite, fired clay brick, fired clay roof tile, and carbonated mineral building material), and investigate which information the dark-field signal entails on the sub-resolution space of the sample. Dark-field tomography at multiple length scale sensitivities was performed at the TOMCAT beamline of the Swiss Light Source (Villigen, Switzerland) using a Talbot grating interferometer. The complementary information of the dark-field modality is most clear in the fired clay brick and roof tile; quartz grains that are almost indistinguishable in the conventional µCT scan are clearly visible in the dark-field owing to their low dark-field signal (homogenous sub-voxel structure), whereas the microporous bulk mass has a high dark-field signal. Large (resolved) pores on the other hand, which are clearly visible in the absorption dataset, are almost invisible in the dark-field modality because they are overprinted with dark-field signal originating from the bulk mass. The experiments also showed how the dark-field signal from a feature depends on the length scale sensitivity, which is set by moving the sample with respect to the grating interferometer

3D Correlative Imaging of Lithium Ion Concentration in a Vertically Oriented Electrode Microstructure with a Density Gradient

The performance of Li+ ion batteries (LIBs) is hindered by steep Li+ ion concentration gradients in the electrodes. Although thick electrodes (≥300 µm) have the potential for reducing the proportion of inactive components inside LIBs and increasing battery energy density, the Li+ ion concentration gradient problem is exacerbated. Most understanding of Li+ ion diffusion in the electrodes is based on computational modeling because of the low atomic number (Z) of Li. There are few experimental methods to visualize Li+ ion concentration distribution of the electrode within a battery of typical configurations, for example, coin cells with stainless steel casing. Here, for the first time, an interrupted in situ correlative imaging technique is developed, combining novel, full-field X-ray Compton scattering imaging with X-ray computed tomography that allows 3D pixel-by-pixel mapping of both Li+ stoichiometry and electrode microstructure of a LiNi0.8 Mn0.1 Co0.1 O2 cathode to correlate the chemical and physical properties of the electrode inside a working coin cell battery. An electrode microstructure containing vertically oriented pore arrays and a density gradient is fabricated. It is shown how the designed electrode microstructure improves Li+ ion diffusivity, homogenizes Li+ ion concentration through the ultra-thick electrode (1 mm), and improves utilization of electrode active materials

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Making Bronze Age solid-hilted swords: from chaînes opératoires to craftsmen

International audienceThere is a long-lasting research tradition around Bronze Age swords, with many publications since the beginning of the 20th century, for example in the framework of the Prähistorische Bronzefunde project. Most studies focus on the evolution of swords’ morphological and ornamental features to build typo-chronological systems. Questions related to craftsmen’s identities, production organisation and exchange networks were mostly addressed thanks to these typological classifications, as stylistic variations have been used to identify products from different workshops. However, we believe this approach is flawed as our knowledge of production organisation is not good enough to assert that the aspect of the swords was determined by craftsmen. Other scenarios where shapes and ornaments are chosen by users, for example if swords are made to order, can be imagined. On the other hand, it seems likely that craftsmen were the only ones involved in the choice of production techniques used to transform a piece of metal into a sword. Studying the variations within the chaîne opératoire of Bronze Age swords therefore appears like a reliable method to address questions related to craftsmen and production groups, and ultimately to discuss production organisation and exchange networks on a sound basis.Although Bronze Age swords’ production techniques were investigated from the end of the 1950s to the 1970s with the development of X-Ray radiography in archaeology, for example in Mainz or in Bonn, there have been a lack of data on the way swords were made. In the last two decades, the development of new techniques such as digital radiography and tomography (CT-scan) enabled a breakthrough in our knowledge of production techniques (fig. 1). Thanks to technological data currently available, we propose the creation of a new tool in addition to the existing typological framework: a techno-typology. This new classification system is purely based on the variations observed at different steps of the chaîne opératoire. Thanks to this tool, we can evaluate the technological homogeneity of swords at the scale of a type, a region or a period, giving us an insight into the organisation of production and the number of production groups providing swords to the users.This new classification based on technological features gives us the opportunity to revisit to history of swords production in Europe during the Bronze Age. Three main phases can be identified:1. Experimental phase (1800-1450 BC): swords are produced in small-scaled and versatile production units experimenting various techniques and processes.2. “Monopoly” phase (1450-900 BC): the few types of swords form a very homogenous technological group; the important standardisation probably corresponds to a centralised production in a few highly specialised workshops.3. Break phase (900-800 BC): major shift in the aspect of the swords coming along with the development of various technological traditions corresponding to the development of many versatile production groups.Each of these phases correspond to cultural variations among both users and craftsmen that can be connected to socio-economic and political changes within Bronze Age societies

Representative size distributions of framboidal, euhedral, and sunflower pyrite from high-resolution X-ray tomography and scanning electron microscopy analyses

A statistical procedure designed to obtain representative size distributions for different morphologies and arrangements of pyrite is described here. This statistical procedure is applied to data acquired during scanning electron microscopy (SEM) and high-resolution X-ray tomography (micro-CT) analyses. The statistical procedure was tested in methane-derived carbonate pipes recovered in the Gulf of Cadiz. These samples contain abundant pyrite together with pseudomorph iron oxyhydroxides showing multiple morphologies including euhedral crystals, framboids, and sunflowers (framboidal core with outer crystals). The SEM analysis consisted in the establishment of independent populations of pyrite and iron oxyhydroxides grouped by morphology and arrangement and the determination of its size distributions. Micro-CT analysis included a determination of the 3D volume of pyrite from the density difference between pyrite and the rest of mineral forming the samples. The use of the micro-CT technique implies that minerals with similar attenuation coefficients than those of pyrite are scarce or not present in the studied samples. A filtering process was applied to the 3D volume. This filtering process consisted of the selection of objects with corrected sphericity greater than 0.80, discrete compactness greater than 0.60, elongation and flatness of the circumscribed 3D ellipsoid less than 1.80 and the sum of the elongation and flatness less than 3. Objects with shapes similar to those expected in pyrite (spheroidal and regular shapes) were selected with this filtering process. The optimal mixture of lognormal size distributions was obtained applying statistical techniques to the entire size distribution represented by the filtered objects. The correspondence between size distributions obtained during the SEM and the micro-CT analyses was done by matching statistical parameters and using 3D renderings. The representative size distributions of pyrite as determined by the proposed 3D processing methodology can be used to accurately quantify the paleo-environmental conditions of pyrite formation, which would solve some of the limitations resulting from analyses based on 2D images.Peer reviewe