Determination of ingredients in packaged pharmaceutical tablets by energy dispersive X‐ray diffraction and maximum likelihood principal component analysis multivariate curve resolution‐alternating least squares with correlation constraint

Energy dispersive X‐ray diffraction (EDXRD) and maximum likelihood principal component analysis multivariate curve resolution‐alternating least squares (MLPCA‐MCR‐ALS) with correlation constraint were used to quantify the composition of packaged pharmaceutical formulations. Recorded EDXRD profiles from unpackaged and packaged samples of ternary mixtures were modelled together in order to recover the concentrations as well as the pure profiles of the constituent compounds. MLPCA was used as a data pretreatment step to MCR‐ALS, accounting for the high noise and nonconstant variance observed in the EDXRD profiles and was shown to improve the resolution accuracy of MCR‐ALS for the data set. Local correlation constraints were applied in the MCR‐ALS procedure in order to model unpackaged and packaged samples simultaneously while accounting for the matrix effect of the packaging materials. The composition of the formulations was estimated with root‐mean‐square error of prediction for each component, including paracetamol, being approximately 2.5 %w/w for unpackaged and packaged samples. Paracetamol concentration was resolved simultaneously for the unpackaged and packaged samples to a greater degree of accuracy than achieved by partial least squares regression (PLSR) when modelling the contexts separately. By modelling the effects of the packaging and incorporating accurate reference information of unpackaged samples into the resolution of packaged samples, the potential of EDXRD and MLPCA‐MCR‐ALS for the identification and quantification of packaged solid‐dosage medicine in nondestructive screening and counterfeit medicine detection has been raised

<i>miniPixD</i>: a compact sample analysis system which combines X-ray imaging and diffraction

This paper introduces miniPixD: a new, compact system that utilises transmission X-ray imaging and X-ray diffraction (XRD) to locate and identify materials of interest within an otherwise opaque volume. The system and the embodied techniques have utility in security screening, medical diagnostics, non-destructive testing (NDT) and quality assurance (QA). This paper outlines the design of the system including discussion on the choice of components and presents some data from relevant samples which are compared to other energy dispersive and angular dispersive XRD techniques

Evaluation of sensors for the detection of energy resolved very soft x-ray fluorescence

Energy-dispersive imaging spectroscopy of X-ray emission from the Earth’s aurorae promises to further knowledge in the field of aeronomy. Time- and spatially-resolved observations of fluorescence from the dominant atmospheric components require the detection of X-rays as soft as 390 eV with a resolution of no more than 100 eV at these energies. The Auroral X-ray Imaging Spectrometer (AXIS) instrument of the Disturbed and quiet time Ionosphere-thermosphere System at High Altitudes (DISHA) mission is expected to perform these observations. The baseline instrument design has suggested the use of an electron-multiplying charge-coupled device (EMCCD). The EMCCD’s electron-multiplying register can reduce the effective readout noise and enable the detection of signals as small as a single photoelectron. For the detection of soft X-rays, however, the noise penalty from the EM register’s stochastic process degrades energy resolution. Emerging CMOS image sensors (CIS), particularly the Teledyne e2v CIS221-X test device, with back illumination, full depletion (with 36 μm thickness), large pixel sizes (40 μm), and low readout noise (3 e- rms effective) are expected to achieve the required performance without the effects of the EM register. Simple models for X-ray event sensitivity, detectability, and resolution, indicate that candidate CIS equal or better EMCCD performance. Furthermore, CIS offer other advantages including lower power consumption, higher operating temperature, and increased radiation hardness. However, these sensors introduce other behaviors that may impact their apparent benefits, which initial experimental testing and analyses are working to understand

X-ray optimised CMOS image sensors for the Auroral X-ray Imaging Spectrometer (AXIS)

The Auroral x-ray Imaging Spectrometer (AXIS) instrument proposed by the Indian Space Research Organisation’s (ISRO) Space Astronomy Group plans to gather spectral information of the Earth’s aurorae in the 0.3 to 3keV band from a low Earth polar orbit for the first time. A trade-off study comparing possible Teledyne e2v (Te2v) detectors to meet preliminary instrument requirements previously concluded that the backside-illuminated (BI) CIS221-X, a prototype CMOS image sensor (CIS) optimised for soft x-ray detection, was a viable option. This paper introduces the current preliminary instrument requirements for AXIS and the compact Nuscis camera electronics from XCAM Ltd that will be used with the CIS221-X to produce an engineering model of the instrument. Continued studies on the CIS221-X for AXIS will include the optimisation of operating conditions in particular for the less well-studied pixel variants of the detector, and calibration with soft x-rays

Multivariate calibration of energy-dispersive X-ray diffraction data for predicting the composition of pharmaceutical tablets in packaging

A system using energy-dispersive X-ray diffraction (EDXRD) has been developed and tested using multivariate calibration for the quantitative analysis of tablet-form mixtures of common pharmaceutical ingredients. A principal advantage of EDXRD over the more traditional and common angular dispersive X-ray diffraction technique (ADXRD) is the potential of EDXRD to analyse tablets within their packaging, due to the higher energy X-rays used. In the experiment, a series of caffeine, paracetamol and microcrystalline cellulose mixtures were prepared and pressed into tablets. EDXRD profiles were recorded on each sample and a principal component analysis (PCA) was carried out in both unpackaged and packaged scenarios. In both cases the first two principal components explained >98% of the between-sample variance. The PCA projected the sample profiles into two dimensional principal component space in close accordance to their ternary mixture design, demonstrating the discriminating potential of the EDXRD system. A partial least squares regression (PLSR) model was built with the samples and was validated using leave-one-out cross-validation. Low prediction errors of between 2% and 4% for both unpackaged and packaged tablets were obtained for all three chemical compounds. The prediction capability through packaging demonstrates a truly non-destructive method for quantifying tablet composition and demonstrates good potential for EDXRD to be applied in the field of counterfeit medicine screening and pharmaceutical quality control

Evaluating UV detector enhancement technologies for the next generation of space telescopes: the path to CASTOR

As space agencies consider the next generation of large space telescopes, it is becoming clear that high performance Ultraviolet (UV) imaging will be a key requirement. High-performing CMOS image sensors that are optimised for UV detection performance will therefore be essential for these missions to be able to fulfil their science requirements. The CASTOR mission, a 1m UV space telescope project, will be utilising the large format CIS303 and CIS120 detectors from Teledyne e2v for three large focal planes covering the UV , u ′ and g ′ bands, respectively. Typically, silicon sensors have a very low quantum efficiency (QE) in the UV band between 150- 300 nm, and the 2d-doping technology from NASA/JPL will therefore be utilised to improve the quantum efficiency. The Open University will perform electro-optical testing and space qualification of the CIS303 and CIS120 detectors, including a comparison of different UV coating and enhancement technologies. This paper covers the specification of radiation testing of the CIS303 and CIS120 detectors at the Open University, and characterisation of the QE-enhancing surface treatments

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms−1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Quantitative energy-dispersive x-ray diffraction for identification of counterfeit medicines: a preliminary study

The prevalence of counterfeit and substandard medicines has been growing rapidly over the past decade, and fast, nondestructive techniques for their detection are urgently needed to counter this trend. In this study, energy-dispersive X-ray diffraction (EDXRD) combined with chemometrics was assessed for its effectiveness in quantitative analysis of compressed powder mixtures. Although EDXRD produces lower-resolution diffraction patterns than angular-dispersive X-ray diffraction (ADXRD), it is of interest for this application as it carries the advantage of allowing the analysis of tablets within their packaging, due to the higher energy X-rays used. A series of caffeine, paracetamol and microcrystalline cellulose mixtures were prepared with compositions between 0 - 100 weight% in 20 weight% steps (22 samples in total, including a centroid mixture), and were pressed into tablets. EDXRD spectra were collected in triplicate, and a principal component analysis (PCA) separated these into their correct positions in the ternary mixture design. A partial least-squares (PLS) regression model calibrated using this training set was validated using both segmented cross-validation, and with a test set of six samples (mixtures in 8:1:1 and 5⅓:2⅓:2⅓ ratios) – the latter giving a root-mean square error of prediction (RMSEP) of 1.30, 2.25 and 2.03 weight% for caffeine, paracetamol and cellulose respectively. These initial results are promising, with RMSEP values on a par with those reported in the ADXRD literature

X-ray backscatter sensing of defects in carbon fibre composite materials

X-ray backscatter (XBS) provides a novel approach to the field of non-destructive evaluation (NDE) in the aerospace industry. XBS is conducted by collecting the radiation which is scattered from a sample illuminated by a well-defined Xray beam, and the technique enables objects to be scanned at a sub-surface level using single-sided access, and without the requirement for coupling with the sample. Single-sided access is of particular importance when the objects of interest are very large, such as aircraft components. Carbon fibre composite materials are being increasingly used as a structural material in aircraft, and there is an increasing demand for techniques which are sensitive to the delaminations which occur in these composites as a result of both large impacts and barely visible impact damage (BVID). The XBS signal is greatly enhanced for plastics and lightweight materials, making it an ideal candidate for probing sub-surface damage and defects in carbon fibre composites. Here we present both computer modelling and experimental data which demonstrate the capability of the XBS technique for identifying hidden defects in carbon fibre

Design and Test of the Jupiter Exploration Camera JANUS

Description of the Architecture, Design, Implementation and Test of the JUICE camera JANUS