Biomedical Engineering Reference
In-Depth Information
particulates such as crystals and powders, light scattering losses can be high
and therefore, a closer working distance can be more beneficial.
Immersion probes are in close proximity to the process materials. In or-
der to protect the internal optics of the probe, the housing, including the
window material, needs to be chemically resistant or withstand the abrasive
nature of moving particles. Immersion probes are typically used for monitoring
the reaction chemistry and drug crystallisation in the primary manufacturing
processing of the drug molecule. Barnes et al. have used an immersion-based
system to monitor the morphological state of a crystalline drug to show the
impact of manufacture hold time, post-crystallisation [11]. The probe was a
short-focus immersion optic to maximise the signal response for the mate-
rial to give the sensitivity needed. Immersion probes have also been used for
monitoring powder processes including blending [12] and drying [13, 14] and
homogenisation of aqueous-based pharmaceutical process [15].
One of the disadvantages of Raman measurements in backreflection mode
is sub-sampling because the laser and Raman collection spots are relatively
small. An example is Raman measurements on tablet formulations where mul-
tipoint measurements or an excitation beam cross-section of the order of a
few millimetres is used to get around this problem [16]. A more elegant ap-
proach for formulated products is transmission Raman [17] whereby the light
is delivered to one side of the sample and collected on the other. A possi-
ble arrangement for this is shown in Fig. 10.4b. Matousek and Parker [18]
and Johansson et al. [19] have demonstrated this as an effective quantitative
approach for bulk properties of pharmaceutical formulations. The light inci-
dent on the sample is internally scattered, generating Raman from the bulk of
the material. A process instrument designed for transmission Raman gives us
significant opportunities for rapid measurements on tablets in a production
environment.
The technical development is still very rapid and addresses the growing
need within process monitoring. The current trend includes further improve-
ment of instrument design for smaller and more rugged equipment, integration
into automated analytical systems and miniaturisation for multiple installa-
tions and portability.
10.4 Raman in Manufacturing Application
There is a fast growing number of Raman applications in the pharmaceutical
industry reported in the literature. Still, the vast majority of these reports are
on lab-based measurements for determination of physical form changes and
fairly little is reported about the use of Raman in pharmaceutical manufac-
turing. In particular, the use of Raman in secondary manufacturing is quite
uncommon. In this review we focus on papers published after year 2000.
Folestad et al. reviewed the role of Raman spectroscopy in secondary man-
ufacturing and discussed a strategy for implementing Raman spectroscopy in
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