Transmission Raman

Since a larger sample volume is presumed to be probed, the use of transmission mode has led to simpler, more accurate models requiring fewer calibration samples [50]. Scientists at AstraZeneca found that with a transmission Raman approach as few as three calibration samples were required to obtain prediction errors nearly equivalent to their full model [42]. For a fixed 10-s acquisition time, the transmission system had prediction errors as much as 30% less than the WAI system, though both approaches had low errors. It is hoped that this approach in combination with advanced data analysis techniques, such as band target entropy minimization (BTEM) [51], might help improve Raman s quantitative sensitivity further. 

P. Matousek and A.W. Parker, Non-invasive probing of pharmaceutical capsules using transmission Raman spectroscopy, J. Raman Spectrosc., 38, 563-567 (2007). 

J. Johansson, A. Sparen, O. Svensson, S. Folestad, and M. Clayboum, Quantitative transmission Raman spechoscopy of pharmaceutical tablets and capsules, Appl. Spectrosc., 61, 1211-1218 (2007). 

Characterisation of Deep Layers of Tissue and Powders Spatially Offset Raman and Transmission Raman Spectroscopy... 

The absence of the subsampling problem in transmission Raman was demonstrated experimentally and computationally by Matousek and Parker [43]. The results of Monte Carlo simulations are shown in Fig. 3.7 re-location of a thin impurity layer from the sample surface to a depth of 3 mm within a typical tablet medium diminishes its conventional backscattering Raman signal by four orders of magnitude. In practical situations, such signal levels are... 

Fig. 3.8. Dielectric band-pass filter used for the enhancement of signals in transmission Raman spectroscopy and a schematic illustration of the shift of the design wavelength with the angle of photon incidence...

Fig. 3.9. Enhancement of transmission Raman signal using a standard dielectric band-pass filter (BF) placed within the laser beam into the proximity of sample. The Raman spectra are those of a standard paracetamol tablet measured with (with band-pass filter) and without (bare) the filter. The spectra are offset for clarity. The acquisition times were 1 s in both cases with a laser power of 250 mW (827 nm). The spectra were detected with an Ocean Optics spectrograph equipped with a detector array cooled to -15° C...

In a number of process analytical technology (PAT) applications in the pharmaceutical industry it is desirable to monitor rapidly and non-invasively the bulk content of drugs with high chemical specificity. Although NIR absorption spectroscopy has been used widely in this area its comparatively low chemical specificity places limits on its usefulness. As noted earlier, transmission Raman is particularly well suited for this application since it removes the key obstacle of conventional Raman, the subsampling problem [43]. Matousek and... 

Parker et al. [45] also demonstrated that the transmission Raman geometry can also dramatically reduce the fluorescence background originating from capsule shells, permitting more sensitive spectroscopic interrogation of the bulk capsule content. This also applies to coated tablets where fluorescence originating from the coating is suppressed. 

Fig. 3.12. Non-invasive Raman spectra of pharmaceutical capsules. The spectra were obtained using a laboratory instrument configured in the transmission Raman geometry and a standard commercial Raman microscope (Renishaw) in conventional backscattering geometry. The Raman spectra of an empty capsule shell (lowest trace) and the capsule content itself (top trace, the capsule content was transferred into an optical cell) are shown for comparison. The dashed lines indicate the principal Raman bands of the capsule and of the API (this figure was published in [65], Copyright Elsevier (2008))...

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

This section will outline the developments of deep Raman spectroscopy from the use of time gating to spatially offset Raman spectroscopy to transmission Raman a sequence of increasing practical probing depth as advances have been made. This is counterbalanced by a reduction in depth selectivity with each new technique. An exploration of the potential use of deep Raman for breast cancer diagnostics will be used to illustrate the potential here. 

Transmission Raman Spectroscopy (TransRaman) for Deep Probing of Calcifications... 

In the transmission Raman approach, the laser beam is incident upon one side of the probed object and the Raman light is collected from the opposite side. 

TRS can be regarded as an extreme example of SORS. Most importantly, Transmission Raman is rapid as it requires no sample preparation and involves no phase change. 

In many pharmaceuhcal and biomedical applicahons, such as the noninvasive probing of colored capsules, coated tablets and subsurface hssue spectroscopy, it is also beneficial that the transmission Raman method very elfechvely diminishes the Raman and fluorescence signals originating from the surface layers of the probed sample compared to conventional backscattering Raman geometry [37]. 

Figure 12.8 shows the results of a feasibility experiment carried out in transmission Raman geometry on a standard paracetamol (acetaminophen) tablet, with and without a bandpass filter. The bandpass filter was centered at 830 nm and its bandwidth was 3.2 nm. The Raman spectra are shown in a raw form, without any numerical preprocessing. A substantial enhancement (x6.5) was observed upon the insertion of the bandpass filter into the proximity of the tablet. Such a large enhancement could be very difficult, and in many cases impossible, to reproduce by other means. The use of a bandpass filter permits the collection of Raman spectra of higher quahty, and consequently a more sensitive analysis of sample can be accompHshed, or higher penetration depths attained. It is also worth noting... 

Figure 12.12 Raman spectra of two types of calcified materials (a 100-300pm-thick layer) recovered from a 16mm-thick slab of chicken tissue ( hap in tissue , com in tissue see text for details). The spectra were obtained by subtracting raw transmission Raman spectra of tissue only from those of tissue containing...

The properties of the transmission Raman geometry are well suited to the requirements of pharmaceutical production lines, thus underlining the potential of this method to displace existing NIR absorption spectroscopy in applications where a higher chemical specificity is required. However, further studies are required to establish the technique s sensitivity limits and to validate its potential. 

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