Biomedical Engineering Reference
In-Depth Information
position as a function of temperature using an immersion probe Raman spec-
trometer. In addition, a comparison with particle size monitoring using fo-
cused beam reflectance measurement (FBRM) showed a good correlation of
the kinetics measured by the two techniques. Kobayashi [35] compared in-line
and at-line Raman spectroscopy, NIR spectroscopy and FBRM particle size
monitoring on a solid-state transition of taltirelin and timepidium bromide in
slurries. It was concluded that Raman spectroscopy is the most suitable of the
techniques for these systems although FBRM is useful for establishing indi-
rect correlation to polymorphic transition. Qu et al. studied a carbamazepine
system in ethanol-water mixtures using in-line Raman spectroscopy to estab-
lish transition mechanism of anhydrous to dihydrated carbamazepine [36]. The
reaction kinetics was concluded to be a two-step process of dissolution of anhy-
drous material and crystallisation of the dihydrated form. Scholl et al. reported
on modelling and monitoring of polymorphic transitions of l-glutamic acid
[37]. The authors combined Raman spectroscopy, NIR spectroscopy, FBRM
and particle vision to study polymorph conversion from
-form.
Caillet et al. developed a calibration model based on relative peak intensities
for both concentration and polymorph ratio of anhydrous and monohydrate
citric acid in water [38]. Reliable models were reported that were mainly in-
sensitive to both solid concentration and scaling up of the reactor volume. It
was commented that the potential issues of sensitivity to particle size distribu-
tion and temperature remain to be studied. Ferrari et al. studied polymorphic
transitions of
α
-form to
β
-form l-glutamic acid [39]. They reported that the
transition rate was dependent on scale of operation of the experiment.
O'Sullivan discussed the influence of particle size on quantitative Raman
monitoring in slurries [40]. A system of
α
-form to
β
-form d-mannitol in toluene in the
presence of sucrose was studied. It was found that although keeping the num-
ber and size of mannitol crystals constant the measured Raman signal varied
with different particle size of the sucrose. These results show that particle size
must always be taken into consideration in quantitative measurements and a
linear relationship can not be taken for granted.
Savolainen et al. investigated the role of Raman spectroscopy for moni-
toring amorphous content and compared the performance with that of NIR
spectroscopy [41]. Partial least squares (PLS) models in combination with sev-
eral data pre-processing methods were employed. The prediction error for an
independent test set was in the range of 2-3% for both NIR and Raman spec-
troscopy for amorphous and crystalline
β
-lactose monohydrate. The authors
concluded that both techniques are useful for quantifying amorphous content;
however, the performance depends on process unit operation. Rantanen et
al. performed a similar study of anhydrate/hydrate powder mixtures of ni-
trofurantoin, theophyllin, caffeine and carbamazepine [42]. They found that
both NIR and Raman performed well and that multivariate evaluation not
always improves the evaluation in the case of Raman data. Santesson et al.
demonstrated in situ Raman monitoring of crystallisation in acoustically levi-
tated nanolitre drops [43]. Indomethazine and benzamide were used as model
α
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