Melt Granulation with polyethylene glycol in a Single Pot Processor

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.