“Filling the gap” in continuous pharmaceutical technologies: A Novel Continuous Filtration and Drying Unit KTP Associate:- Dr. Simon Coleman CMAC/University of Strathclyde:- Dr. Chris Price, Dr. Paul Mulheran Alconbury Weston Ltd:- Alastair Barton, Paul Firth, Richard Sutherland Innovate UK: Dr. Russ Bromley
Introduction
• An innovative continuous filtration technology has been designed and manufactured at Alconbury Weston Ltd (AWL)
• The system uses a carousel mechanism to filter wash and dry mini-batches simultaneously in a continuous manner ? • A KTP project was setup to develop and optimise AWL’s continuous filtration equipment for pharmaceutical manufacture
• Part of this project was to optimise the drying stages of the process Continuous Crystallisation Continuous Milling/Tableting
Phase 1 Phase 2&3 Phase 4 Phase 5 Phase 6 Phase 7 Suspension Feed Cake Solvent De-liquoring Convection Cake & Filtration Washing Exchange Drying Discharge • A complete plant, replacing a traditional 2 to 3 floor batch production facility! - Fits into walk-in fume cupboard!
• Entry-to-exit time in minutes… not hours!
• From feasibility through optimization to production on a single Port 1 Port 2&3 Port 4 Port 5 Port 6,7,8,9 Port 10 validateable platform!
• Vision system improves product purity, yields and quality attributes
Nitrogen Cake Flow Discharge • Improved wash efficiency - reduced solvent usage
• Reduced energy and waste, lower footprint
• Minimum throughput, Maximum Data… Optimization of isolation process achieved with only a few sample runs
AWL Continuous Carousel Filter Dryer (CCFD)
Methodology for Drying Experiments Results
• A drying kinetics rig was designed to replicate the drying stage Temperature profiles for 50 mm cakes Flow meter in the CCFD using the following conditions: Temperature above cake • Solid:- Sodium Bicarbonate Temperature below cake The drying rate & LOD for this system: 0.003 – 0.0065 g/s and 0.3 – 2.0% Heat Solvent:- Water 50 50 Transfer respectively
Starting moisture content:- 25 wt% C) Line o 40 40 Drying Time:- 10 minutes 45oC 30 30 • The temperature profiles demonstrate 20 20 the effect of evaporative cooling • The components of the rig was setup in the following order: 10 10 Temperature ( Temperature • The ‘spikes’ in temperature are due to - Compressed air inlet 0 0 Drying Port - Pressure regulator the intermittent removal of the drying 0 100 200 300 400 500 600 0 100 200 300 400 500 600 port for drying rate measurement - Flow meter Inlet 50 50
- Heat transfer line C) o 40 40 • - Drying port with filter plate The time of the temperature 30 Inlet Temperature Setpoint Temperature Inlet 30 - Drying receiver vessel inflection in the outlet temperature is - Pressure transmitter Thermocouple o 20 20 assumed to be the time when solvent above cake 25 C 10 10 has evaporated
- Vacuum pump ( Temperature 0 0 • 0 100 200 300 400 500 600 0 100 200 300 400 500 600 The CCFD will be adapted to include the measurement of temperature • Drying rate was captured by Time (s) Inlet Pressure Time (s) removing the port and measuring its 0.25 bar 2 bar below the cake to capture an online Thermocouple estimation for drying weight intermittently during drying Outlet below cake
• A DoE was carried out: • Analysis of the DoE data demonstrated the significance of the pressure of the inlet drying gas, suggesting an inlet pressure of 1 bar was required for optimal drying in this system Drying Factors Responses Receiver Inlet Temperature (25 – 45 oC) Drying rate • Future units will therefore require a pressurised system to allow for optimal drying Inlet Pressure (0.25 – 2 bar) Loss on Drying Cake height (20 – 50 mm) Agglomeration • This experimental data will contribute towards the development of a drying model to Time of temperature inflection further understand the effect of pressure on drying
“The project has allowed me to be introduced to many leading “The success of this KTP project has changed the way “The KTP has enabled us to establish a significant lead specialists, expanding my academic and industry networks.” AWL will approach any major product development.” in the field of isolation of pharmaceutical products.”
Dr. Simon Coleman, KTP Associate Alastair Barton, AWL Managing Director Dr. Chris Price, University of Strathclyde & CMAC
What’s Next? Acknowledgements: - West of Scotland KTP Centre • Continuous Carousel Filter for large throughput has been designed, aiming towards full-scale production unit (90+ tonnes/annum) - Chris Steven, Previous KTP Associate • KTP Associate to take up the position of Product Manager for Isolation and Drying at AWL – assisting the sales team to increase CCFD sales globally - Sara Ottoboni, PhD student at UoS • The KTP project contributes towards the ultimate goal of achieving end-to-end continuous processes by assisting AWL to become the global leader in - Muhid Shahid, PhD student at UoS Continuous Filtration and Drying equipment - All the members of the AWL team