MONITORING GRANULATION
PROCESSES USING IN-LINE NEAR
INFRARED SPECTROSCOPY
ranulation is an important
step in pharmaceutical
solid dosage form
processing. The flow and
compression characteristics of a
formulation are improved through
granulation. A common method of
pharmaceutical granulation is top
spray granulation, where the powder
is fluidized in a fluid bed dryer and
liquid binder solution is sprayed
onto the product layer from the top
counter-currently to the fluidizing
gas. After spraying the liquid into the
formulation and forming the granule
the product must be dried to the
proper moisture level. If the granules
are over-dried the action of the
fluid bed can cause the fracture of
granules creating undesirable fines
and can damage the formulation
due to hydration changes in some
actives and excipients. If the granules
are not dry enough the product will
not flow properly and can cake and
cause problems with subsequent
processing, including product
sticking to the faces of the tablet
press punches and problems with
product stability during storage.
G
Samples typically are withdrawn from
the fluid bed during processing and
analysed off-line in a laboratory for
moisture content. Commonly there
is a delay before analysis results
are available to the operator that
causes processing decisions, like
end-point determination, to be made
without optimal product moisture
information. Top spray granulation
end point is often based on time
or product temperature and not
moisture content. Near-infrared
(NIR) spectroscopy is a rapid non-
destructive technique often used for
in-process analysis of moisture in the
manufacturing environment.
Real-time measurements can be made
with no sample preparation and the
data can be analysed and stored
automatically. NIR fits in well with
the Process Analytical Technology
(PAT) initiative as developed by
FDA. One of the elements of the PAT
initiative is to use in-line analysis to
increase process understanding and
control to verify product quality and
release it for subse quent processing
without delay. Using NIR the process
can be monitored for low levels of
residual moisture and alcohols and
other process constituents to yield
better process control and end-point
determination.
The Metrohm Process Analytics XDS
Analyser with Fiber Optic interface can
be used with a special probe design
to fit typical Single Pot Granulators.
The probe has an angled face that
forces the powder sample to divert
in a quasi-laminar flow over the
measurement window. This maintains
a more constant sample density at the
window interface.
As such the whole process can be
monitored accurately for multiple
components and typically moisture
levels, solvent levels and average
particle size can be monitored in real
time to provide information to make
rapid process decisions improving
product quality, consistency and
saving money.
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