Fluidised bed characterisation using Raman spectroscopy: Applications to pharmaceutical processing

This study investigates a model system for potential pharmaceutical materials in fluidised bed processes. In particular, this study proposes a novel use of Raman spectroscopy, which allows in situ measurement of the composition of the material within the fluidised bed in three spatial dimensions and as a function of time. This is achieved by recording Raman spectra from specific volumes of space. The work shows that Raman spectroscopy can be used to provide 3D maps of the concentration and chemical structure of the particles in a fluidised bed within a relatively short (120 s) time window. At the most basic level the technique measures particle density via the intensity of the Raman spectra, however this could be used. More importantly the data are also rich in spectroscopic information on the chemical structure of the fluidised particles which is useful either for monitoring a given granulation process or more generally for the analysis of the dynamics of the airflow if the data were incorporated into an appropriate model. The technique has the potential to give detailed in situ information on how the structure and composition of the granules/powders within the fluidised bed (dryer or granulator) vary with the position and evolve with time. (c) 2007 Elsevier Ltd. All rights reserved.

Multivariate prediction of clarified butter composition using Raman spectroscopy

Raman spectroscopy has been used to predict the abundance of the FA in clarified butterfat that was obtained from dairy cows fed a range of levels of rapeseed oil in their diet. Partial least squares regression of the Raman spectra against FA compositions obtained by GC showed good prediction for the five major (abundance >5%) FA with R-2=0.74-0.92 and a root mean SE of prediction (RMSEP) that was 5-7% of the mean. In general, the prediction accuracy fell with decreasing abundance in the sample, but the RMSEP was 1.25%. The Raman method has the best prediction ability for unsaturated FA (R-2=0.85-0.92), and in particular trans unsaturated FA (best-predicted FA was 18:1 tDelta9). This enhancement was attributed to the isolation of the unsaturated modes from the saturated modes and the significantly higher spectral response of unsaturated bonds compared with saturated bonds. Raman spectra of the melted butter samples could also be used to predict bulk parameters calculated from standard analyzes, such as iodine value (R-2=0.80) and solid fat content at low temperature (R-2=0.87). For solid fat contents determined at higher temperatures, the prediction ability was significantly reduced (R-2=0.42), and this decrease in performance was attributed to the smaller range of values in solid fat content at the higher temperatures. Finally, although the prediction errors for the abundances of each of the FA in a given sample are much larger with Raman than with full GC analysis, the accuracy is acceptably high for quality control applications. This, combined with the fact that Raman spectra can be obtained with no sample preparation and with 60-s data collection times, means that high-throughput, on-line Raman analysis of butter samples should be possible.

Determination of the degree of dissociation in an inductively coupled hydrogen plasma using optical emission spectroscopy and laser diagnostics

Gas temperature is of major importance in plasma based surface treatment, since the surface processes are strongly temperature sensitive. The spatial distribution of reactive species responsible for surface modification is also influenced by the gas temperature. Industrial applications of RF plasma reactors require a high degree of homogeneity of the plasma in contact with the substrate. Reliable measurements of spatially resolved gas temperatures are, therefore, of great importance. The gas temperature can be obtained, e.g. by optical emission spectroscopy (OES). Common methods of OES to obtain gas temperatures from analysis of rotational distributions in excited states do not include the population dynamics influenced by cascading processes from higher electronic states. A model was developed to evaluate this effect on the apparent rotational temperature that is observed. Phase resolved OES confirmed the validity of this model. It was found that cascading leads to higher apparent temperatures, but the deviation (~25 K) is relatively small and can be ignored in most cases. This analysis is applied to investigate axially and radially resolved temperature profiles in an inductively coupled hydrogen RF discharge.

Recent applications of Chemical Imaging to pharmaceutical process monitoring and quality control

Chemical Imaging (CI) is an emerging platform technology that integrates conventional imaging and spectroscopy to attain both spatial and spectral information from an object. Vibrational spectroscopic methods, such as Near Infrared (NIR) and Raman spectroscopy, combined with imaging are particularly useful for analysis of biological/pharmaceutical forms. The rapid, non-destructive and non-invasive features of CI mark its potential suitability as a process analytical tool for the pharmaceutical industry, for both process monitoring and quality control in the many stages of drug production. This paper provides an overview of CI principles, instrumentation and analysis. Recent applications of Raman and NIR-CI to pharmaceutical quality and process control are presented; challenges facing Cl implementation and likely future developments in the technology are also discussed. (C) 2007 Elsevier B.V. All rights reserved.

Quantitative surface-enhanced Raman spectroscopy

The purpose of this tutorial review is to show how surface-enhanced Raman (SERS) and resonance Raman (SERRS) spectroscopy have evolved to the stage where they can be used as a quantitative analytical technique. SER(R)S has enormous potential for a range of applications where high sensitivity needs to be combined with good discrimination between molecular targets, particularly since low cost, compact spectrometers can read the high signal levels that SER(R)S typically provides. These advantages over conventional Raman measurements come at the cost of increased complexity and this review discusses the factors that need to be controlled to generate stable and reproducible SER(R)S calibrations.

Absolute Atomic Oxygen Density Measurements by Two-Photon Absorption Laser-induced Fluorescence Spectroscopy in an RF-Excited Atmospheric Pressure Plasma Jet

The atmospheric pressure plasma jet is a capacitively coupled radio frequency discharge (13.56 MHz) running with a high helium flux (2m3 h-1) between concentric electrodes. Small amounts (0.5%) of admixed molecular oxygen do not disturb the homogeneous plasma discharge. The jet effluent leaving the discharge through the ring-shaped nozzle contains high concentrations of radicals at a low gas temperature—the key property for a variety of applications aiming at treatment of thermally sensitive surfaces. We report on absolute atomic oxygen density measurements by two-photon absorption laser-induced fluorescence (TALIF) spectroscopy in the jet effluent. Calibration is performed with the aid of a comparative TALIF measurement with xenon. An excitation scheme (different from the one earlier published) providing spectral matching of both the two-photon resonances and the fluorescence transitions is applied.

Characterisation of fluidised bed granulation processes using in situ Raman spectroscopy

Previous work by the authors Walker et al. [2007b. Fluidised bed characterisation using Raman spectroscopy: applications to pharmaceutical processing. Chemical Engineering Science 62, 3832–3838] illustrated that Raman spectroscopy could be used to provide 3-D maps of the concentration and chemical structure of particles in motion in a fluidised bed, within a relatively short (120 s) time window. Moreover, we reported that the technique, as outlined, has the potential to give detailed in-situ information on how the structure and composition of granules/powders within the fluidised bed (dryer or granulator) vary with the position and evolve with time. In this study we extended the original work by shortening the time window of the Raman spectroscopic analysis to 10 s, which has allowed the in-situ real-time characterisation of a fluidised bed granulation process. Here we show an important new use of the technique which allows in-situ measurement of the composition of the material within the fluidised bed in three spatial dimensions and as a function of time. This is achieved by recording Raman spectra using a probe positioned within the fluidised bed on a long-travel x–y–z stage. In these experiments the absolute Raman intensity is used to provide a direct measure of the amount of any given material in the probed volume, i.e. a particle density. Particle density profiles have been calculated over the granulation time and show how the volume of the fluidised bed decreases with an increase mean granule size. The Raman spectroscopy analysis indicated that nucleation/coalescence in this co-melt fluidised hot melt granulation system occurred over a relatively short time frame (t<30 s). The Raman spectroscopic technique demonstrated accurate correlation with independent granulation experiments which provided particle size distribution analysis. The similarity of the data indicates that the Raman spectra accurately represent solids ratios within the bed, and thus the techniques quantitative capabilities for future use in the pharmaceutical industry.

Purification of imidazolium ionic liquids for spectroscopic applications

Ionic liquids are often contaminated by colored impurities. These impurities can be problematic for spectroscopic studies or for monitoring organic reactions by UV/Vis spectroscopy. The effect of different purification methods on the optical quality of colored ionic liquids was studied and compared. Yellowish ionic liquids can partially be decolorized by treatment with active charcoal or by recrystallization. Our experiments show column liquid chromatography is not always a good technique to prepare spectrograde imidazolium halide ionic liquids. Colorless and UV-transparent ionic liquids were synthesized by a method that can exclude the need for further purification steps. (c) 2005 Elsevier B.V. All rights reserved.

Perturbed frequency-selective surfaces fabricated on large thin polymer membranes for multiband infrared applications

The design, fabrication, and characterization of single-screen perturbed frequency-selective surfaces (FSS) at infrared frequencies for single and multiband applications are reported. Single-band FSS based on parallel strips have been perturbed by decreasing the length of every second strip within the array in order to achieve dual band-stop responses. The same principle has been extended to design FSS exhibiting tri- and quadreflection bands. In addition, strip FSSs have been perturbed by replacing every second strip for a metallic ring, resulting in dual-band filters with different polarization responses of the bands. These designs have been fabricated on large thin polyimide membranes using sacrificial silicon wafers. An oxide interlayer between the sacrificial silicon wafer and the polyimide membrane is employed to stop the silicon etching and is wet etched subsequently by a solution of ammonium fluoride and acetic acid that does not attack either the polyimide membrane or the aluminium FSS elements. Fourier transform infrared spectroscopy measurements are presented to validate the predicted responses of the fabricated prototypes.

Thin film composite optical waveguides for sensor applications: a review

We review the design and fabrication of thin-film composite optical waveguides (OWG) with high refractive index for sensor applications. A highly sensitive optical sensor device has been developed on the basis of thin-film, composite OWG. The thin-film OWG was deposited onto the surface of a potassium-ion-exchanged (K+) glass OWG by sputtering or spin coating (5-9 mm wide, and with tapers at both ends). By allowing an adiabatic transition of the guided light from the secondary OWG to the thin-film OWG, the electric field of the evanescent wave at the thin film was enhanced. The attenuation of the guided light in the thin film layer was small, and the guided light intensity changed sensitively with the refractive index of the cladding layer. Our experimental results demonstrate that thin-film, composite OWG gas sensors or immunosensors are much more sensitive than sensors based on other technologies. (c) 2004 Elsevier B.V. All rights reserved.

An introduction to biological nuclear magnetic resonance spectroscopy

ABSTRACT Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical techniques available to biology. This review is an introduction to the potential of this method and is aimed at readers who have little or no experience in acquiring or analyzing NMR spectra. We focus on spectroscopic applications of the magnetic resonance effect, rather than imaging ones, and explain how various aspects of the NMR phenomenon make it a versatile tool with which to address a number of biological problems. Using detailed examples, we discuss the use of 1H NMR spectroscopy in mixture analysis and metabolomics, the use of 13C NMR spectroscopy in tracking isotopomers and determining the flux through metabolic pathways (‘fluxomics’) and the use of 31P NMR spectroscopy in monitoring ATP generation and intracellular pH homeotasis in vivo. Further examples demonstrate how NMR spectroscopy can be used to probe the physical environment of a cell by measuring diffusion and the tumbling rates of individual metabolites and how it can determine macromolecular structures by measuring the bonds and distances which separate individual atoms. We finish by outlining some of the key challenges which remain in NMR spectroscopy and we highlight how recent advances— such as increased magnet field strengths, cryogenic cooling, microprobes and hyperpolarisation—are opening new avenues for today’s biological NMR spectroscopists.

Max separation clustering for feature extraction from Optical Emission Spectroscopy Data

This paper proposes max separation clustering (MSC), a new non-hierarchical clustering method used for feature extraction from optical emission spectroscopy (OES) data for plasma etch process control applications. OES data is high dimensional and inherently highly redundant with the result that it is difficult if not impossible to recognize useful features and key variables by direct visualization. MSC is developed for clustering variables with distinctive patterns and providing effective pattern representation by a small number of representative variables. The relationship between signal-to-noise ratio (SNR) and clustering performance is highlighted, leading to a requirement that low SNR signals be removed before applying MSC. Experimental results on industrial OES data show that MSC with low SNR signal removal produces effective summarization of the dominant patterns in the data.