Biomedical Engineering Reference
In-Depth Information
NIR, Raman would be expected to offer advantages such as ease of use for
quantitative analysis. The reason for less widespread use of process Raman
spectroscopy is due in part to more expensive equipment, relative to NIR.
A broader implementation of process Raman spectroscopy in the pharma-
ceutical industry has previously also been hampered by inherent weaknesses
in sampling in remote measurements on solids. This is discussed further in
Section 10.3.
10.2 Strategic Role of Raman Spectroscopy for PAT
Raman spectroscopy for PAT measurements holds some interesting features
such as non-destructive analysis of solids, semi-solids and solid-state transfor-
mations. In addition, sampling times as short as down to hundreds of millisec-
onds offer possibilities for high throughput analysis, which are key in process
monitoring and control applications. Ultimately this allows for process in-
tervention if needed. An additional feature is that many common packaging
materials (e.g. plastics) are transparent when conducting Raman spectroscopy
in the NIR wavelength range, which makes direct inspection of packaged ma-
terials possible. As has been discussed above, Raman spectroscopy has the
capability to distinguish chemical materials that differ only in physical state.
This can be taken advantage of both in spectroscopic and in imaging ap-
plications, e.g. allowing for determination of spatial distributions of different
ingredients in composite samples such as tablets, capsules and granules. Fur-
thermore, this opens new opportunities for monitoring changes in the physical
state of a chemical as an effect of processing, e.g. changes in the polymorphic
form of the active pharmaceutical ingredient.
An adequate strategy for when and where to apply Raman spectroscopy-
based measurements in manufacturing processing applications is outlined in
Figs. 10.2 and 10.3. The strategic role of Raman in process monitoring and
control of chemical content and homogeneity is outlined in Fig. 10.2 for pri-
mary and secondary manufacturing processing and for bioprocessing, respec-
tively. Analogously, the strategic role of Raman in process monitoring and
control of crystallinity and polymorphism is outlined in Fig. 10.3. The under-
pinning science for this strategy emanates both from the intrinsic features of
Raman spectroscopy, as briefly discussed above, and from the review of recent
PAT examples demonstrated in the scientific literature. These examples are
further discussed in the Section 10.4, where technical details for the various
applications are given.
The dashed boxes in Figs. 10.2 and 10.3 represent typical unit operations
that are more strategic to monitoring and control through use of Raman spec-
troscopy, depending on what materials are processed. For example, in primary
manufacturing of active pharmaceutical ingredients, the strategic unit opera-
tions where application of Raman spectroscopy adds value, typically concerns
the synthesis and crystallisation process steps. Notably, demonstrated appli-
Search WWH ::
Custom Search