Spatial resolution of drug crystallisation in the skin by X-ray micro-computed tomography

Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 – 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery

Strain in epitaxial MnSi films on Si(111) in the thick film limit studied by polarization-dependent extended x-ray absorption fine structure

We report a study of the strain state of epitaxial MnSi films on Si(111) substrates in the thick film limit (100-500~\AA) as a function of film thickness using polarization-dependent extended x-ray absorption fine structure (EXAFS). All films investigated are phase-pure and of high quality with a sharp interface between MnSi and Si. The investigated MnSi films are in a thickness regime where the magnetic transition temperature $T_\mathrm{c}$ assumes a thickness-independent enhanced value of $\geq$43~K as compared with that of bulk MnSi, where $T_\mathrm{c} \approx 29~{\rm K}$. A detailed refinement of the EXAFS data reveals that the Mn positions are unchanged, whereas the Si positions vary along the out-of-plane [111]-direction, alternating in orientation from unit cell to unit cell. Thus, for thick MnSi films, the unit cell volume is essentially that of bulk MnSi --- except in the vicinity of the interface with the Si substrate (thin film limit). In view of the enhanced magnetic transition temperature we conclude that the mere presence of the interface, and its specific characteristics, strongly affects the magnetic properties of the entire MnSi film, even far from the interface. Our analysis provides invaluable information about the local strain at the MnSi/Si(111) interface. The presented methodology of polarization dependent EXAFS can also be employed to investigate the local structure of other interesting interfaces.Comment: 11 pages, 10 figure

Correlations in nano-scale step fluctuations: comparison of simulation and experiments

We analyze correlations in step-edge fluctuations using the Bortz-Kalos-Lebowitz kinetic Monte Carlo algorithm, with a 2-parameter expression for energy barriers, and compare with our VT-STM line-scan experiments on spiral steps on Pb(111). The scaling of the correlation times gives a dynamic exponent confirming the expected step-edge-diffusion rate-limiting kinetics both in the MC and in the experiments. We both calculate and measure the temperature dependence of (mass) transport properties via the characteristic hopping times and deduce therefrom the notoriously-elusive effective energy barrier for the edge fluctuations. With a careful analysis we point out the necessity of a more complex model to mimic the kinetics of a Pb(111) surface for certain parameter ranges.Comment: 10 pages, 9 figures, submitted to Physical Review

Imaging Cerenkov emission as a quality assurance tool in electron radiotherapy

A new potential quality assurance (QA) method is explored (including assessment of depth dose, dose linearity, dose rate linearity and beam profile) for clinical electron beams based on imaging Cerenkov light. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured in Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the dose at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. A simulation was also performed of the deposited energy and of Cerenkov production in water using GEANT4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in GEANT4, to attempt to reproduce Cerenkov images. Simulations of the deposited energy and the Cerenkov light production agreed with each other for a pencil beam of electrons, while for a realistic field size, Cerenkov production in the build-up region overestimated the dose by +8%

<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

Preservation of the metaproteome: variability of protein preservation in ancient dental calculus.

Proteomic analysis of dental calculus is emerging as a powerful tool for disease and dietary characterisation of archaeological populations. To better understand the variability in protein results from dental calculus, we analysed 21 samples from three Roman-period populations to compare: 1) the quantity of extracted protein; 2) the number of mass spectral queries; and 3) the number of peptide spectral matches and protein identifications. We found little correlation between the quantity of calculus analysed and total protein identifications, as well as no systematic trends between site location and protein preservation. We identified a wide range of individual variability, which may be associated with the mechanisms of calculus formation and/or post-depositional contamination, in addition to taphonomic factors. Our results suggest dental calculus is indeed a stable, long-term reservoir of proteins as previously reported, but further systematic studies are needed to identify mechanisms associated with protein entrapment and survival in dental calculus

Fluctuations, line tensions, and correlation times of nanoscale islands on surfaces

We analyze in detail the fluctuations and correlations of the (spatial) Fourier modes of nano-scale single-layer islands on (111) fcc crystal surfaces. We analytically show that the Fourier modes of the fluctuations couple due to the anisotropy of the crystal, changing the power spectrum of the fluctuations, and that the actual eigenmodes of the fluctuations are the appropriate linear combinations of the Fourier modes. Using kinetic Monte Carlo simulations with bond-counting parameters that best match realistic energy barriers for hopping rates, we deduce absolute line tensions as a function of azimuthal orientation from the analyses of the fluctuation of each individual mode. The autocorrelation functions of these modes give the scaling of the correlation times with wavelength, providing us with the rate-limiting kinetics driving the fluctuations, here step-edge diffusion. The results for the energetic parameters are in reasonable agreement with available experimental data for Pb(111) surfaces, and we compare the correlation times of island-edge fluctuations to relaxation times of quenched Pb crystallites.Comment: 11 pages, 8 figures; to appear in PRB 70, xxx (15 Dec 2004), changes in MC and its implication

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