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Scalable flow reactor technology
vrt
TM
technology
vrtTM technology is an automated and sophisticated plug flow reactor system that enables processes developed using micro reactor systems to be directly scaled to the kilo / plant level. The technology is broadly applicable for a vast range of chemistry. vrtTM technology enables process optimisation at scale to demonstrate robustness, productivity, safety, quality and economic benefit and provides the basis for a full scale commercial manufacturing design specification. vrtTM technology has been exemplified for a number of multi-ton commercial products within the Fine Chemical and Pharmaceutical Manufacturing sectors.
Continuous Flow Process Development vrtTM technology is specifically designed for intermediate scale-up to kilo and pilot plant scale development. The development of a flow process can be divided into three distinct stages:-
Three Distinct Stages of Development of a Flow Process
•
develop the chemistry and outline the process
•
consolidate selection
•
carry out initial screening of the process parameter envelope
•
produce kilo scale quantities of material
•
optimise the process to d e mo n s t r a t e s a f et y , quality, robustness, productivity and economic benefit
•
provide the basis for fullscale commercial manufacturing design specification
•
full-scale commercial manufacture
STAGE 1 Laboratory Based Experimental Design
Stage 1: Laboratory Based Experimental Design Stage 2: Intermediate Scale-up Kilo/Plant Scale Stage 3: Full Scale Commercial Manufacture There are many commercial micro reactor systems available for completing laboratory based experimental design (stage 1). However technology for progressing beyond the laboratory is less developed. STAGE 2
The concept of ‘scaling-out’ or ‘parallelisation’ of micro reactor processes has been extensively documented as an alternative to conventional scale-up, although in reality there are limited real-case examples of this approach. ‘Parallelisation’, by its very nature, builds complexity into a process. Whereas a more desirable goal for most organisations would be risk reduction through simplicity. The lack of a general purpose scale-up tool for flow processing is one of the major contributors to such processes remaining within the domain of the laboratory and never realising the advantages of continuous flow. vrtTM technology overcomes this shortcoming because it is specifically designed for intermediate scale-up to kilo/pilot plant scale (stage 2) development and provides the foundation for continuous flow based commercial manufacture (stage 3).
Intermediate Scale-up to Kilo/ Pilot Plant Scale
route
STAGE 3 Full Scale Commercial Manufacture
2/4
Innovation through Continuous Processing Improving the manufacturing process both economically and sustainably is a primary objective for fine chemical and pharmaceutical manufacturing. Continuous flow processing is widely recognised as technology to achieve this objective. Continuous processing enables cleaner, leaner and more energy efficient processes to be developed and offers substantial investment, technological and safety advantages. • Investment Advantages e.g. low capital costs; small footprint—high throughput; minimal scale-up problems; improved efficiency; using less raw materials, and lower operational costs
Commercial Process Developed Using
vrtTM
• Technological Advantages e.g. safely handle energetic chemistry; develop shorter, more economic processes; telescope processes together; readily integrate with realtime monitoring & control (PAT), and deliver higher yield, higher purity
• Safety & Environmental Advantages e.g. small inventory at any one time, reducing hazard & risk; remotely operated plant control; reduced operational exposure; reduced emissions level; more energy efficient, and reduced waste
vrt
TM
Technology Illustration
In the graphics, colour represents quality and the required quality of the output is represented by the light green.
Initially the process is operated with a residence time of 31 units, resulting in over conversion (‘brown’ product).
The residence time is reduced to 7 units resulting in slight under conversion (‘light blue’ product).
Finally the residence time is tweaked’ to 9 time units resulting in the desired ‘light green’ product.
Variable Residence Time vrtTM technology uses well characterised heat exchangers and conventional static mixers for achieving the necessary heat and mass transfer required for a flow process. The most important parameter for a plug flow process is residence time because this ultimately governs the product composition and quality. The ability to vary residence time on-line is extremely desirable because it enables rapid optimisation and tuning of the process at scale. However, for a static mixer based reactor, varying residence time by simply changing flow rate is not an option because the flow rate governs heat and mass transfer. vrtTM technology overcomes this limitation by enabling residence time within the systems parameters to be accessed without changing flow rate. Stylistically the vrtTM is a static mixer that can be stretched or compressed at will to achieve any desirable residence time. 3/4
Example Product Specification Parameter
Description
vrt TM Application
Appropriate for kilo-lab to pilot-scale to full-scale usage
Output
kilogram to tonnes
Design flow-rate
100 mL/minute
Residence time
5 to 75 seconds (5 sec intervals), longer times available (Note 1 below)
Operating pressure
2 – 100 bar Typically -20 – 120o C
Operating temperature Flow stability
+/- 1.0% of set-point
Static mixers
1/4” or 3/16”
Reynolds number
~500 (at flow rate 100 mL/min)
Back pressure
2 – 100 bar
Automation Materials
Industrial PLC interface Stainless steel, C22 or C276 Hastelloy; PTFE or PFA (low pressure only)
Regulatory compliance
Options
Compliant Available on request e.g. integration with liquid-liquid extraction, on-line monitoring, gaseous inputs etc
Note 1 VRT Technology enables reactions to be accelerated by employing higher temperatures / pressures whilst maintaining product integrity and selectivity, hence a residence time of 75 seconds will be sufficient for the majority of processes.
Automation: User/Control Interface
Contact:
Operational control is clear and intuitive due to the simple nature of the equipment. Flows, residence times, pressures and temperatures are manipulated using a graphical interface.
Sapien Process Technologies Newton Hall Town Street, Newton Cambridge, UK CB22 7ZE
Experiment design including preparation and purging is simply sequenced and integrated with the analysis and sampling requirements.
Tel: Fax:
+44 1223 870213 +44 1223 872983
Email: [email protected] Web: www.sapien-equipment.com
Process information is plotted in real time and all data logged to a database. vrtTM technology is a joint venture between Sapien Process Technologies and Phoenix Chemicals
evolution of intelligent process equipment
Sapien VRT Publication 10g, April 2008
4/4
vrt
TM
technology
vrtTM technology is an automated and sophisticated plug flow reactor system that enables processes developed using micro reactor systems to be directly scaled to the kilo / plant level. The technology is broadly applicable for a vast range of chemistry. vrtTM technology enables process optimisation at scale to demonstrate robustness, productivity, safety, quality and economic benefit and provides the basis for a full scale commercial manufacturing design specification. vrtTM technology has been exemplified for a number of multi-ton commercial products within the Fine Chemical and Pharmaceutical Manufacturing sectors.
Continuous Flow Process Development vrtTM technology is specifically designed for intermediate scale-up to kilo and pilot plant scale development. The development of a flow process can be divided into three distinct stages:-
Three Distinct Stages of Development of a Flow Process
•
develop the chemistry and outline the process
•
consolidate selection
•
carry out initial screening of the process parameter envelope
•
produce kilo scale quantities of material
•
optimise the process to d e mo n s t r a t e s a f et y , quality, robustness, productivity and economic benefit
•
provide the basis for fullscale commercial manufacturing design specification
•
full-scale commercial manufacture
STAGE 1 Laboratory Based Experimental Design
Stage 1: Laboratory Based Experimental Design Stage 2: Intermediate Scale-up Kilo/Plant Scale Stage 3: Full Scale Commercial Manufacture There are many commercial micro reactor systems available for completing laboratory based experimental design (stage 1). However technology for progressing beyond the laboratory is less developed. STAGE 2
The concept of ‘scaling-out’ or ‘parallelisation’ of micro reactor processes has been extensively documented as an alternative to conventional scale-up, although in reality there are limited real-case examples of this approach. ‘Parallelisation’, by its very nature, builds complexity into a process. Whereas a more desirable goal for most organisations would be risk reduction through simplicity. The lack of a general purpose scale-up tool for flow processing is one of the major contributors to such processes remaining within the domain of the laboratory and never realising the advantages of continuous flow. vrtTM technology overcomes this shortcoming because it is specifically designed for intermediate scale-up to kilo/pilot plant scale (stage 2) development and provides the foundation for continuous flow based commercial manufacture (stage 3).
Intermediate Scale-up to Kilo/ Pilot Plant Scale
route
STAGE 3 Full Scale Commercial Manufacture
2/4
Innovation through Continuous Processing Improving the manufacturing process both economically and sustainably is a primary objective for fine chemical and pharmaceutical manufacturing. Continuous flow processing is widely recognised as technology to achieve this objective. Continuous processing enables cleaner, leaner and more energy efficient processes to be developed and offers substantial investment, technological and safety advantages. • Investment Advantages e.g. low capital costs; small footprint—high throughput; minimal scale-up problems; improved efficiency; using less raw materials, and lower operational costs
Commercial Process Developed Using
vrtTM
• Technological Advantages e.g. safely handle energetic chemistry; develop shorter, more economic processes; telescope processes together; readily integrate with realtime monitoring & control (PAT), and deliver higher yield, higher purity
• Safety & Environmental Advantages e.g. small inventory at any one time, reducing hazard & risk; remotely operated plant control; reduced operational exposure; reduced emissions level; more energy efficient, and reduced waste
vrt
TM
Technology Illustration
In the graphics, colour represents quality and the required quality of the output is represented by the light green.
Initially the process is operated with a residence time of 31 units, resulting in over conversion (‘brown’ product).
The residence time is reduced to 7 units resulting in slight under conversion (‘light blue’ product).
Finally the residence time is tweaked’ to 9 time units resulting in the desired ‘light green’ product.
Variable Residence Time vrtTM technology uses well characterised heat exchangers and conventional static mixers for achieving the necessary heat and mass transfer required for a flow process. The most important parameter for a plug flow process is residence time because this ultimately governs the product composition and quality. The ability to vary residence time on-line is extremely desirable because it enables rapid optimisation and tuning of the process at scale. However, for a static mixer based reactor, varying residence time by simply changing flow rate is not an option because the flow rate governs heat and mass transfer. vrtTM technology overcomes this limitation by enabling residence time within the systems parameters to be accessed without changing flow rate. Stylistically the vrtTM is a static mixer that can be stretched or compressed at will to achieve any desirable residence time. 3/4
Example Product Specification Parameter
Description
vrt TM Application
Appropriate for kilo-lab to pilot-scale to full-scale usage
Output
kilogram to tonnes
Design flow-rate
100 mL/minute
Residence time
5 to 75 seconds (5 sec intervals), longer times available (Note 1 below)
Operating pressure
2 – 100 bar Typically -20 – 120o C
Operating temperature Flow stability
+/- 1.0% of set-point
Static mixers
1/4” or 3/16”
Reynolds number
~500 (at flow rate 100 mL/min)
Back pressure
2 – 100 bar
Automation Materials
Industrial PLC interface Stainless steel, C22 or C276 Hastelloy; PTFE or PFA (low pressure only)
Regulatory compliance
Options
Compliant Available on request e.g. integration with liquid-liquid extraction, on-line monitoring, gaseous inputs etc
Note 1 VRT Technology enables reactions to be accelerated by employing higher temperatures / pressures whilst maintaining product integrity and selectivity, hence a residence time of 75 seconds will be sufficient for the majority of processes.
Automation: User/Control Interface
Contact:
Operational control is clear and intuitive due to the simple nature of the equipment. Flows, residence times, pressures and temperatures are manipulated using a graphical interface.
Sapien Process Technologies Newton Hall Town Street, Newton Cambridge, UK CB22 7ZE
Experiment design including preparation and purging is simply sequenced and integrated with the analysis and sampling requirements.
Tel: Fax:
+44 1223 870213 +44 1223 872983
Email: [email protected] Web: www.sapien-equipment.com
Process information is plotted in real time and all data logged to a database. vrtTM technology is a joint venture between Sapien Process Technologies and Phoenix Chemicals
evolution of intelligent process equipment
Sapien VRT Publication 10g, April 2008
4/4
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