This study compares different processing methods to prepare a melt
granulation with polyethylene glycol (PEG) in a high shear mixer / single pot
processor. For melting the PEG, either the heated jacket or heated jacket
supplemented with microwaves was used to supply the necessary energy. For
cooling the mass after granulation, 3 methods were compared: cooling with the
jacket, cooling with pressurized air and cooling with liquid nitrogen.
The results of the comparison show a significant time reduction in
the process when using microwave energy for heating the product, and liquid
nitrogen for cooling. No differences in granule particle size distribution
could be observed.
Melt agglomeration is a process by which agglomeration – or size enlargement
by which fine particles are bound together to agglomerates or granulates – is
obtained through the addition of either a molten binder liquid or a solid
binder which melts during the process. Agglomerates are formed by agitation of
the mixture. To obtain a stable, dry granule, a cooling to ambient temperature
is necessary to solidify the binder.
Recently, the interest in melt
agglomeration processes from the pharmaceutical industry has grown steadily
because of the advantages the technique offers over conventional wet
granulation methods:
- When the binder is added in solid form, the liquid addition step is
avoided, simplifying the equipment, the process and the cleaning.
- As no liquid is added, the drying phase – often the most time-consuming
step in a conventional process – is eliminated.
- When the binder used is insoluble in water, melt agglomeration may present
a simple way to form sustained release formulations.
Many different procedures and equipment have been used for melt
agglomeration. High shear mixers are very well suited to execute a melt
agglomeration process: the high shear forces caused by the impeller rotation
make it easier to obtain a uniform distribution of the molten binder, and
generate enough frictional heat to assist the melting process. High shear
mixers have also been shown to be suitable for melt pelletization, due to the
high shearing forces, plus the bowl shape.
In a high shear mixer almost
all procedures for melt agglomeration and melt pelletization use the heat
supplied by the heated jacket of the bowl and/or the development of heat caused
by friction to melt the binder. In production scale equipment the heating of
the product using the jacket can be very time-consuming (1). The application of
an external heating source, independent from the jacket of the bowl or from the
generation of friction heat, might prove to be more time-efficient.
The
first part of this study investigates the possibility of using microwave energy
as an external heating source to melt the binder. These trials used pilot scale
equipment and compared the process with regard to process time and granule
particle size, using either the heated jacket or microwaves as the energy
source.
The second part of the study focuses on the cooling phase of
the process, which is necessary to obtain a dry, stable granule. In many cases,
this phase is the most time-consuming of the whole melt granulation process due
to the limited cooling capacity of the jacket of the high shear mixer and an
insulation effect of the binder itself. The aim was to shorten the cooling time
by using pressurized air or liquid nitrogen to reduce the temperature of the
product.