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B. Igne and E. W. Ciurczak
and the distance between the paddle and the sensing window) and the quality of
spectral signal.
18.4.2.2 Granulation and Drying
When a powder flows poorly and is not amenable to high speed processing, powder
consolidation can be used to improve its flow characteristics using a solvent and
binder, compaction, or heat to create granules. In wet granulation, a solvent (usually
water) and binder (in solid or liquid form) are added to the powder along with shear to
create aggregates. The solvent is then removed through drying. A granulation process
will result in particles of much larger sizes and density than the initial powders. NIRS
has been used to monitor the particle growth, homogeneity, and solvent level after
drying.
High-shear wet granulators and fluid bed dryers are the most common types of
batch granulator and dryers. Since NIR has a very strong water signal, it has been
used to monitor the water level of the granules during granulation and drying. Frake
et al. used the technology to monitor the granulation end-point in a fluid bed dryer
[56]. Another study looked at how the NIR signal could be used to monitor granule
growth in a fluid bed dryer [57]. Corresponding work in a high-shear wet granulator
was performed using the change in slope of the NIR spectra as a function of physical
differences during the process [58].
The removal of the granulation solvent can also be monitored and potentially
controlled by NIRS. Fluid bed drying is most commonly used. An example of method
development and validation for the monitoring of water was published [59]. Alcalà
et al. showed the suitability of NIRS for the prediction of granule bulk density [60].
Figure 18.8 shows an example of fluid bed granulation and drying process trajectory. After a brief phase of mixing without solvent (dry mixing), the water is added
and then removed. The first two principal components clearly show a combination of
water and particle size information with the water content increasing and decreasing
to a similar level, but with a powder physical property shifting significantly.
Twin-screw granulation is a continuous wet granulation method used in continuous manufacturing lines. Granule quality and the impact of processing parameters
such as liquid feed rate, moisture content, and screw configuration were investigated
by NIR chemical imaging [61]. Authors showed that the visualization capability of
the technology allowed the characterization of the unit operation as the entirety of
the produced materials can be analyzed in-line and in real time, accelerating process
development and improving understanding.
Dry compression does not use a solvent but physical force to consolidate powder
into granules of larger particle size. The density of the ribbons and particle size
distribution of the resulting granules are parameters that have been investigated by
NIRS [62].
Hot melt extrusion uses heat and shear to embed the API with polymers creating
an extrudate with high homogeneity and increased bioavailability for API with low
solubility. A probe can be attached to the die of the extruder to monitor the properties
B. Igne and E. W. Ciurczak
and the distance between the paddle and the sensing window) and the quality of
spectral signal.
18.4.2.2 Granulation and Drying
When a powder flows poorly and is not amenable to high speed processing, powder
consolidation can be used to improve its flow characteristics using a solvent and
binder, compaction, or heat to create granules. In wet granulation, a solvent (usually
water) and binder (in solid or liquid form) are added to the powder along with shear to
create aggregates. The solvent is then removed through drying. A granulation process
will result in particles of much larger sizes and density than the initial powders. NIRS
has been used to monitor the particle growth, homogeneity, and solvent level after
drying.
High-shear wet granulators and fluid bed dryers are the most common types of
batch granulator and dryers. Since NIR has a very strong water signal, it has been
used to monitor the water level of the granules during granulation and drying. Frake
et al. used the technology to monitor the granulation end-point in a fluid bed dryer
[56]. Another study looked at how the NIR signal could be used to monitor granule
growth in a fluid bed dryer [57]. Corresponding work in a high-shear wet granulator
was performed using the change in slope of the NIR spectra as a function of physical
differences during the process [58].
The removal of the granulation solvent can also be monitored and potentially
controlled by NIRS. Fluid bed drying is most commonly used. An example of method
development and validation for the monitoring of water was published [59]. Alcalà
et al. showed the suitability of NIRS for the prediction of granule bulk density [60].
Figure 18.8 shows an example of fluid bed granulation and drying process trajectory. After a brief phase of mixing without solvent (dry mixing), the water is added
and then removed. The first two principal components clearly show a combination of
water and particle size information with the water content increasing and decreasing
to a similar level, but with a powder physical property shifting significantly.
Twin-screw granulation is a continuous wet granulation method used in continuous manufacturing lines. Granule quality and the impact of processing parameters
such as liquid feed rate, moisture content, and screw configuration were investigated
by NIR chemical imaging [61]. Authors showed that the visualization capability of
the technology allowed the characterization of the unit operation as the entirety of
the produced materials can be analyzed in-line and in real time, accelerating process
development and improving understanding.
Dry compression does not use a solvent but physical force to consolidate powder
into granules of larger particle size. The density of the ribbons and particle size
distribution of the resulting granules are parameters that have been investigated by
NIRS [62].
Hot melt extrusion uses heat and shear to embed the API with polymers creating
an extrudate with high homogeneity and increased bioavailability for API with low
solubility. A probe can be attached to the die of the extruder to monitor the properties