Spray drying agglomeration/granulation processes aim to produce particles with
a big surface/mass ratio, i.e. small particles. The reconstitution in water of
a powder consisting of small particles is, however, difficult and requires
intensive mixing in order to disperse the powder before it is totally
dissolved. Bigger particles exhibit a better dispersion, but the solubility is
negatively affected during the drying operation. Agglomeration obtains both a
good dispersion and a complete solution.
Granulation methods
Single pot
A mixer/granulator that dries granules in the same
equipment without discharging is commonly called a single pot. The granulation
is done in a normal high shear processor; however, care must be taken to avoid
the formation of lumps as they cannot be broken down before drying.
Drying options for single-pot systems: the traditional heat source
comes from the dryer walls, which are heated; the boiling temperature and
vacuum are used to reduce and remove vapours. The heat transfer is related to
the surface area of the dryer walls and the volume of product treated.
Therefore, this direct heating method is only effective for small scale use.
The introduction of stripping gas into the pot allows large scale
operation – a small quantity of gas is introduced in the bottom of the
equipment, which passes through the product bed, improving the heat flow from
the wall into the product. The gas also improves the efficiency of vapour
removal.
Microwave energy can be used to overcome these limitations –
providing a further source of energy and has the additional advantage, with
organic solvents, that only pure organic vapours must be treated on the exhaust
side, and not a mixture of solvent and large volumes of process gas, as would
be required in most other wet granulation technologies.
Fluid
bed top spray granulation
Fluid beds fitted with spray nozzles can
perform granulation and, during the last 10 years, fluid beds have improved
dramatically in response to single pot technology competition. It is possible
to have completely closed material handling by a closed linking with upstream
and downstream equipment. Fully automatic cleaning (clean-in-place CIP and
wash-in-place WIP) in fluid beds, using stainless steel filters, now compare
favourably with what is possible in a single pot.
High shear
granulation/fluid bed drying combination
This system allows full
integration with upstream and downstream equipment, and even includes a wet
mill between the granulator and dryer. With modern control systems it is easy
to load, mix and granulate a second batch in the high shear granulator whilst
drying the previous batch in the fluid bed prior to discharge. All equipment
can be CIP in a single, automatic process. Whereas a single shaker might be
acceptable for drying applications, a twin shaker or blowback filter design
should be used for granulation processes.
Continuous fluid bed
granulation
The equipment is filled with raw material (similar to
a batch unit). After the material has been granulated, the process is switched
to the continuous mode, allowing material to be introduced via the rotary inlet
valve and discharged as granules by a second outlet valve. The process can be
controlled by monitoring the pressure drop over the product bed. The inlet air
is segmented, which allows the product in different areas to be treated with
different temperatures. Although the process is essentially plug flow, a
significant amount of back mixing occurs during processing.
Fluidized Spray Drying (FSD™)
Fluidized Spray
Drying produces granules from a liquid in a one-step process. One option is to
produce the active in the primary production as granules, so that it only
requires blending with excipients suitable for direct compression for secondary
processing. This can only be done with actives that are tacky (in a wet state),
otherwise the additio n o f a binder
is necessary. Another use of the FSD™ technology is to mix all the ingredients
into a solution or suspension and to produce granules in a one-step operation.
The liquid feed is atomized at the top of the tower in a co-current
mode during the FSD™ process. After the liquid is evaporated, the particles
generated leave the drying chamber together with the exhaust air. These
particles are then separated in a cyclone or filter and reintroduced into the
drying chamber where they come into contact with wet droplets and form
agglomerates. After these agglomerates have reached a certain weight they
cannot leave via the top of the tower with the exhaust air, but fall down into
the integrated fluid bed at the bottom of the drying chamber. Here they are
dried and cooled before being discharged.
Heat sensitive
materials
To successfully treat heat sensitive materials, the
temperatures and exposure time must be carefully controlled, as should the
presence of moisture and oxygen. Single-pot technology provides safe drying
under vacuum, particularly if the granulation is done with organic solvents –
because the corresponding temperature is even lower. In a spray dryer, however,
relatively high temperatures are involved, but only for a very short time. A
batch fluid bed granulator can operate at higher air inlet temperatures while
spraying and during the beginning of drying, reducing the inlet temperature
afterwards to maintain a low product temperature.
The nature of the
product dictates which is the more appropriate treatment.