Real Time Monitoring of Twin Screw Granulation
It is increasingly recognised that the future of oral solid dose pharmaceutical manufacturing will include greater adoption of continuous manufacturing techniques. Twin-Screw Wet Granulation has emerged as an important continuous manufacturing technology for consistent, repeatable high-quality production of both standard and complex dosage forms. Many of the products employing continuous strategies, however, are still in clinical development. This, coupled with the ever-increasing regulatory requirement for a Quality by Design(QbD) approach, contributes to the challenges faced by the process development engineer. New Process Analytical Technology(PAT) technologies are now being used to decrease the process engineer’s workload, allowing for overall faster process development while delivering the level of process understanding required to build an appropriate process control strategy.
Process development engineers are eager to see QbD evidence that PAT does allow for overall faster process development and that it can work effectively with wet and sticky product typical during processing of some pharmaceutical formulations. They are also seeking more evidence of PAT as an effective tool to enable scale-up of continuous processes and correlate the data generated to more traditional off -line measurement tools.
A new experimental plan to build a data-driven process map for twin-screw granulation was recently carried out by Thermo Scientific using the Pharma 11 Twin-screw Extruder with in-line real time non-product contact particle size PAT (Eyecon2, Innopharma Technology) installed at the screw outlet.
The conclusions from these experiments included:
1. PAT is a valuable tool to analyse, develop and scale-up continuous processes. In particular, IIIIIn-Line real time data
• Fluctuation in the process
• Process stability
2. Twin screw granulation as a continuous process offers the possibility to develop and iiiiiimprove the process while it is running and use of PAT facilitates data-driven selection and oiioptimisation of critical process parameters including
• Liquid-to-solid ratio
• Filling level of the screws (influenced by screw speed, throughput, screw iconfiguration)
To download full application note click here
Additional Twin Screw Granulation Application Notes
During continuous wet granulation quality attributes such as granule size, active pharmaceutical ingredient (API) and excipient content can have an effect on the overall quality of the materials produced. The control of granulation processes can be challenging and currently, there are limited process analytical techniques (PAT) available for the monitoring and control of these processes. For more evidence on how PAT allows for rapid process understanding during product development please download the application notes below.
Measuring In-Line Wet Granule Size on a GEA Consigma 25
Click here to download the application note on a trial carried out in collaboration with the University of Ghent to monitor wet granule size at the outlet of the twin screw granulator on a GEA Consigma 25. During this trail change in particle size was tracked directly during processing and provided particle size data and direct images of the particles in real time.
Detecting Real-Time Process Perturbations on a Thermo Scientific Twin Screw Granulator
Click here to download the application note on a trial developed in collaboration with the University of Strathclyde and GlaxoSmithKline where The Eyecon™ Particle Characteriser was trialled at GlaxoSmithKline, Stevenage to evaluate its ability to detect process perturbations of a 16 mm Thermo Scientific twin screw granulator (TSG) through the monitoring of particle size of wet granules on-line and in real time.