The comilling process plays an important role in solid oral dosage manufacturing. In this process, the granulated products are comminuted to the required size distribution through collisions created from a rotating impeller. In addition to predicting particle size distribution, there is a need to predict other critical quality attributes (CQAs) such as bulk density and tapped density, as these impact tablet compaction behavior. A comprehensive modeling approach to predict the CQAs is needed to aid continuous process modeling in order to simulate interaction with the tablet press operation. In the current work, a full factorial experiment design is implemented to understand the influence of granule strength, impeller speed and residual moisture content on the CQAs. A population balance modeling approach is applied to predict milled particle size distribution and a partial least squares modeling approach is used to predict bulk and tapped density of the milled granule product. Good agreement between predicted and experimental CQAs is achieved. An R^2 value of 0.9787 and 0.7633 is obtained when fitting the mean particle diameters of the milled product and the time required to mill the granulated material respectively.

• Rutgers, The State University of New Jersey

• Oral doses
• Modeling

1. Breakage
2. Conical
3. modeling
4. N/A
5. Oral doses
6. Partial least squares model
7. population balance model
8. Review article
9. Screen mill