(343e) Effect of Scale up On Compaction Properties of High Drug Load Granulation Prepared by Foam Technology

Process scale-up is one of the challenges of wet granulation technology. The ultimate goal in scale-up is to keep granulation properties and the final drug product quality attributes constant. Foam technology (Dow Chemical Co.) has been recently introduced to the pharmaceutical industry with potential to improve control of the high shear wet granulation process. The objective of this study was to assess the critical parameters of the foam granulation unit operation and evaluate its impact on the various

physico-mechanical properties of the resultant granules prepared at different scales.

Method:

Batches (80.5% w/w drug A) were prepared using continuous addition of foam at 65 L (10 kg) and 300 L (50 kg) scale. A foamed hydroxy propyl cellulose (HPC) solution, with. 90% foam quality was used for all trials. The quality of foam is expressed as the ratio of the air to the liquid on volume basis. 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. Particle size, bulk density, flow, pore size distribution, compaction profile and elasticity of the granulations were characterized. Attempts were made to assess the impact of the scale-up on the granulation properties. Scale-up predictors like tip speed and dimensionless number (Froud number) were applied to scale-up the impeller speed of the high shear granulator.

Results:

Data demonstrated that the extent of compaction decreases with an increase in scale size. Irrespective of the scale size, comparable elasticity value (>10%) was obtained for the

65 L and 300 L scales. The 300 L scale batches presented a decrease in the granule porosity as opposed to the 65 L batches.

Conclusion:

The scale-up trials using foamed binder can be accomplished easily and in general resulted in comparable granule properties prepared at both scales. However, granule properties such as porosity and compactibility 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.