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Mozharov S.,University of Strathclyde | Nordon A.,University of Strathclyde | Littlejohn D.,University of Strathclyde | Wiles C.,Chemtrix BV | And 3 more authors.
Journal of the American Chemical Society | Year: 2011

A novel method has been devised to derive kinetic information about reactions in microfluidic systems. Advantages have been demonstrated over conventional procedures for a Knoevenagel condensation reaction in terms of the time required to obtain the data (fivefold reduction) and the efficient use of reagents (tenfold reduction). The procedure is based on a step change from a low (e.g., 0.6 μL min-1) to a high (e.g., 14 μL min-1) flow rate and real-time noninvasive Raman measurements at the end of the flow line, which allows location-specific information to be obtained without the need to move the measurement probe along the microreactor channel. To validate the method, values of the effective reaction order n were obtained employing two different experimental methodologies. Using these values of n, rate constants k were calculated and compared. The values of k derived from the proposed method at 10 and 40 °C were 0.0356 ± 0.0008 mol-0.3 dm 0.9 s-1 (n = 1.3) and 0.24 ± 0.018 mol -0.1 dm0.3 s-1 (n = 1.1), respectively, whereas the values obtained using a more laborious conventional methodology were 0.0335 ± 0.0032 mol-0.4 dm1.2 s-1 (n = 1.4) at 10 °C and 0.244 ± 0.032 mol-0.3 dm0.9 s -1 (n = 1.3) at 40 °C. The new approach is not limited to analysis by Raman spectrometry and can be used with different techniques that can be incorporated into the end of the flow path to provide rapid measurements. © 2011 American Chemical Society.

Townshend N.,University of Strathclyde | Nordon A.,University of Strathclyde | Littlejohn D.,University of Strathclyde | Myrick M.,University of South Carolina | And 2 more authors.
Analytical Chemistry | Year: 2012

A total of 383 tablets of a pharmaceutical product were analyzed by backscatter and transmission Raman spectrometry to determine the concentration of an active pharmaceutical ingredient (API), chlorpheniramine maleate, at the 2% m/m (4 mg) level. As the exact composition of the tablets was unknown, external calibration samples were prepared from chlorpheniramine maleate and microcrystalline cellulose (Avicel) of different particle size. The API peak at 1594 cm-1 in the second derivative Raman spectra was used to generate linear calibration models. The API concentration predicted using backscatter Raman measurements was relatively insensitive to the particle size of Avicel. With transmission, however, particle size effects were greater and accurate prediction of the API content was only possible when the photon propagation properties of the calibration and sample tablets were matched. Good agreement was obtained with HPLC analysis when matched calibration tablets were used for both modes. When the calibration and sample tablets are not chemically matched, spectral normalization based on calculation of relative intensities cannot be used to reduce the effects of differences in physical properties. The main conclusion is that although better for whole tablet analysis, transmission Raman is more sensitive to differences in the photon propagation properties of the calibration and sample tablets. © 2012 American Chemical Society.

Everall N.,Intertek | Priestnall I.A.N.,Intertek | Dallin P.,Clairet Scientific Ltd | Andrews J.,Clairet Scientific Ltd | And 4 more authors.
Applied Spectroscopy | Year: 2010

A practical methodology is described that allows measurement of spatial resolution and sensitivity of Raman spectroscopy in backscatter and transmission modes under conditions where photon migration dominates, i.e., with turbid or opaque samples. For the first time under such conditions the width and intensity of the point spread function (PSF) has been accurately measured as a function of sample thickness and depth below the surface. In transmission mode, the lateral resolution for objects in the bulk degraded linearly with sample thickness, but the resolution was much better for objects near either surface, being determined by the diameter of the probe beam and collection aperture irrespective of sample thickness. In other words, buried objects appear to be larger than ones near either surface. The absolute transmitted signal decreased significantly with sample thickness, but objects in the bulk yielded higher signals than those at either surface. In transmission, materials are sampled preferentially in the bulk, which has ramifications for quantitative analysis. In backscattering mode, objects near the probed surface were detected much more effectively than in the bulk, and the resolution worsened linearly with depth below the surface. These results are highly relevant in circumstances in which one is trying to detect or image buried objects in opaque media, for example Raman tomography of biological tissues or compositional and structural analysis of pharmaceutical tablets. Finally, the observations were in good agreement with Monte Carlo simulations and, provided one is in the diffusion regime, were insensitive to the choice of transport length, which shows that a simple model can be used to predict instrument performance for a given excitation and collection geometry. © 2010 Society for Applied Spectroscopy.

Allan P.,University of Strathclyde | Bellamy L.J.,University of Strathclyde | Bellamy L.J.,Glaxosmithkline | Nordon A.,University of Strathclyde | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

A 785nm diode laser and probe with a 6mm spot size were used to obtain spectra of stationary powders and powders mixing at 50rpm in a high shear convective blender. Two methods of assessing the effect of particle characteristics on the Raman sampling depth for microcrystalline cellulose (Avicel), aspirin or sodium nitrate were compared: (i) the information depth, based on the diminishing Raman signal of TiO2 in a reference plate as the depth of powder prior to the plate was increased, and (ii) the depth at which a sample became infinitely thick, based on the depth of powder at which the Raman signal of the compound became constant. The particle size, shape, density and/or light absorption capability of the compounds were shown to affect the " information" and " infinitely thick" depths of individual compounds. However, when different sized fractions of aspirin were added to Avicel as the main component, the depth values of aspirin were the same and matched that of the Avicel: 1.7mm for the " information" depth and 3.5mm for the " infinitely thick" depth. This latter value was considered to be the minimum Raman sampling depth when monitoring the addition of aspirin to Avicel in the blender. Mixing profiles for aspirin were obtained non-invasively through the glass wall of the vessel and could be used to assess how the aspirin blended into the main component, identify the end point of the mixing process (which varied with the particle size of the aspirin), and determine the concentration of aspirin in real time. The Raman procedure was compared to two other non-invasive monitoring techniques, near infrared (NIR) spectrometry and broadband acoustic emission spectrometry. The features of the mixing profiles generated by the three techniques were similar for addition of aspirin to Avicel. Although Raman was less sensitive than NIR spectrometry, Raman allowed compound specific mixing profiles to be generated by studying the mixing behaviour of an aspirin-aspartame-Avicel mixture. © 2012.

Townshend N.,University of Strathclyde | Nordon A.,University of Strathclyde | Littlejohn D.,University of Strathclyde | Andrews J.,Clairet Scientific Ltd. | Dallin P.,Clairet Scientific Ltd.
Analytical Chemistry | Year: 2012

Transmission Raman measurements of a 1 mm thick sulfur-containing disk were made at different positions as it was moved through 4 mm of aspirin (150-212 μm) or microcrystalline cellulose (Avicel) of different size ranges (<38, 53-106, and 150-212 μm). The transmission Raman intensity of the sulfur interlayer at 218 cm-1 was lower when the disk was placed at the top or bottom of the powder bed, compared to positions within the bed and the difference between the sulfur intensity at the outer and inner positions increased with Avicel particle size. Also, the positional intensity difference was smaller for needle-shaped aspirin than for granular Avicel of the same size. The attenuation coefficients for the propagation of the exciting laser and transmitted Raman photons through the individual powders were the same but decreased as the particle size of Avicel increased; also, the attenuation coefficients for propagation through 150-212 μm aspirin were almost half of those through similar sized Avicel particles. The study has demonstrated that particulate size and type affect transmitted Raman intensities and, consequently, such factors need to be considered in the analysis of powders, especially if particle properties vary between the samples. © 2012 American Chemical Society.

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