(571o) The Use of Foam in High Shear Wet Granulation: Effect of Scale up On Granules Quality Attributes

High shear wet granulation is a common pharmaceutical unit operation for forming agglomerates. The API under study offered challenges during processing due to its low bulk density, low particle size, and its adhesive nature when in contact with water. To address the above challenges a new granulation process was employed whereby liquid binders are added as aqueous foam. Experiments indicate that foam granulations require less water than granulations where the binder solution is added as liquid. Rates of addition of foam can be greater than rates of addition of sprayed liquids, and foam can even be added in a single portion to the granulator. The objective of this study was to asses the impact of scale-up on the quality attributes of the granules. Batches using the foam granulation technique were manufactured at pilot and commercial scales and the manufacturability as well as the granule quality attributes were assessed.

The quality of foam is expressed as the ratio of the air to the liquid on volume basis. A foamed hydroxy propyl cellulose (HPC) solution, with 90% foam quality was used for all trials Batches (80.5% w/w API) were prepared using continuous addition of foam at 65 L (10 kg) and 300 L (50 kg) scale. The 65 L batches were prepared with 34% w/w foamed HPC solution while the 300 L batches were prepared with 34% w/w and 36% w/w foamed HPC solution. The small change in binder was studied because the high drug loading and challenging API properties might result in changes to the granule quality attributes even for this relatively small change in water content. Particle size, bulk density, flow, pore size distribution, and compaction properties of the granules were characterized. Comparisons were made to assess the impact of the scale-up on the granule quality attributes.

Batches were successfully manufactured at commercial (300 L) with out processing issues. Data demonstrated that physical properties of the granules (particle size, bulk density, and powder flow) were comparable between the 65 L and 300 L scales. Analysis of the compaction data indicate that the extent of compaction decreases with an increase in scale. The 300 L scale batches showed a decrease in the granule porosity as opposed to the 65 L batches. Dissolution profiles were comparable at both scales even though the porosity of granules changed upon scale-up.

The scale-up trials using foamed binder can be accomplished easily and in general resulted in comparable granule physical properties prepared at both scales. However, compaction properties and porosity of the granules changed upon scale-up. The results suggest that scale-up effects reported during scale-up of conventional wet granulation may also be observed with foam granulation.