(677b) Optimizing Continuous Twin-Screw Wet Granulation for a Batch to Continuous Conversion

Qiushi Zhou,

Fernando Muzzio

Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, New Jersey 08854-8058, United States

Continuous manufacturing has advantages in increasing process efficiency, product quality, and reducing operating cost comparing to the traditional batch manufacturing process. Continuous wet granulation is one of the most important methods that has been widely used among downstream pharmaceutical manufacturing. This project shows the feasibly of converting a high-shear batch granulation to a continuous twin-screw granulation method. Particle sizes of granules can be predicted by the model generated, resulting in particle sizes that match the high-shear batch granulation process.

To determine the ideal design space of the twin-screw granulator, a preliminary design space study was used to define the range of working conditions. After obtaining the condition range, a face centered cubic design was used in the focused design space. The particle size was the key resultant factor that was monitored. The results from the DoE showed that screw speed had less influence on the particle size than both the L/S ratio and alcohol content. The results suggested that a clear trend in particle size was observed for L/S ratio and granulation fluid composition. Particle size decreased with an increase in alcohol content in the granulation fluid and a decrease in the L/S ratio. Combining the data from the preliminary design space study and designed experiments enable the determination of a stepwise regression that was able to predict granules properties.