Successful implementation of Continuous Manufacturing technology requires real time product quality monitoring that can result into rejection strategies for material manufactured outside process control limits. In a twin screw granulation process, parameters like water content, powder feed rate, and granulator screw speed can influence granule quality. Deviations in any of these parameters from the set-point may affect granule quality. Having a sound diversion strategy in place can help divert these implicated granules to waste. Residence time distribution experiments were conducted on a 16-mm Thermo Fisher twin screw granulator (TSG) for a range of process parameters, and the data was modelled to predict the needed diversion time as a function of process parameters. Scale-up from the 16-mm to 24-mm granulator was evaluated and data was found to scale based on mass per unit volume of granulator (channel fill), thus enabling 16-mm data to scale to 24-mm. The diversion strategy proposed is based on utilizing a wash out curve derived from residence time distribution to quantify the maximum concentration of implicated material that could be present in the next downstream unit operation(s) (e.g. a fluid bed dryer) and ensuring it is less than a suitable threshold to prevent product quality impact.

• GlaxoSmithKline
• Rowan University

• PAT
• Oral solid dose

1. Continuous manufacturing / UV visible spectroscopy /Near infrared spectroscopy / Tracer
2. Diversion strategy / Control strategy
3. Diversion to waste / Channel fill
4. oral solid dose
5. pat
6. Research Article
7. Residence time distribution / Scale-up / Hold-up
8. Twin screw granulator / Granulation
9. Wash out curve / Design space