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Scale up??
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Scale Up Getting New products To Market Main Causes of Problems Research & Development
Manufacturing
Store Dates are Set
Prototype Changes
Cost Estimates
Product Approval
Greatest Product
Break Even Cost
Date Commitments
Better Mouse Trap
Marketing
Past Experiences
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Scale Up 4 Keys to Success Keep Process Cooling Time Constant Equalize High Shear Mixing Energy Transfer apply the same high shear energy WHAT ?????? SURE !!!! at the sameHOW?????? batch temperature for the same amount of time
Maintain Uniformity - Good Mixing Keep Transfer Times Constant (rate of Dilution )
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The Energy Box
Temperature Heating/Cooling
Times
Transfer/ Mixing Times High Energy Mixing 11 Copying of this Information Prohibited without Permission
Scale Up Full Spectrum of Product Types
Easy Products
Products From Hell
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Scale Up Generic - High Viscosity Mixing Vessel Domed Cover for Pressure and Vacuum Processing
Countra-sweep Drive/Motor
Outer Blade
Kettle Jacket
Inner Blade
Scraper Blades
Temperature Probe
High Shear Mixer
Product Outlet High Shear Drive/Motor Copying of this Information Prohibited without Permission
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Scale Up High Flow and High Shear Homogenizer Heads
Stator Rotor
Stator Rotor
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Scale Up Time Constant Process Operations Maintain Uniformity - Good Mixing Cooling Time
Emulsification / transfer time High Shear Mixing
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X = 1.116
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Scale Up Volume vs Heat Transfer Area
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Scale Up Heat Transfer Rate
Q = (Uo) x (A) x (delta t) lm Q = Quantity of Heat per unit Time Uo = rate factor (overall heat transfer coefficient)
A = heat transfer surface Area delta t = mean temperature differential between batch and cooling media
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Scale Up Surface Area/Liter vs Vessel Size Sq.Feet of Surface Area/Liter of Volume vs Kettle Volume (liters) 0.180 0.160
Sq.Ft/Liter
0.140
Q = (Uo) x (A) x (delta t)
lm
0.120 0.100 0.080 0.060 0.040 0.020 0.000 0
500
1000
1500
2000
2500
3000
3500
4000
Kettle Volume (Liters)
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Scale Up Manufacturing Temperature Profile
Temperature (Deg C
Batch temperature vs Time 90 80 70 60 50 40 30 20 10 0 Time 20 Copying of this Information Prohibited without Permission
Scale Up Pilot Plant Temperature Profile
Temperature (Deg C
Batch temperature vs Time 90 80 70 60 50 40 30 20 10 0 Time
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Scale Up Manufacturing and Pilot Plant Temperature Profile
Temperature (Deg C
Batch temperature vs Time 90 80 70 60 50 40 30 20 10 0
•Surface Area •Installation •Kettle •Cooling System •Cooling Media
Time 22 Copying of this Information Prohibited without Permission
Scale-up Cooling “The Double-edged Sword”
Cooling Times are the Same No Shock Out at Kettle Wall
Cooling Times Are Not the Same Shorter mix time Crystalline or wax structure could be different
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Scale Up High Shear Mixing - Homogenizers Only Homogenizers? No - Also large diameter props in large kettles Adverse Effects Particle identity loss Gum breakdown Structural breakdown
emulsion crystalline structure 24 Copying of this Information Prohibited without Permission
Scale Up Types of Homogenizers In-Line Advantages
Can Control Work Input accurately - if used with a positive displacement feed pump Can easily be used across many batch sizes if using a two kettle operation
Back Pressure valve
Positive Displacement Pump
Inline Homogenizer
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Scale Up Types of Homogenizers In Kettle Advantages Very High Batch Turn Over (as long as viscosity is low)
Remember Both types act like a centrifical pump - as viscosity increases flow rate through the homogenizer decreases
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Scale Up Developing Energy Translation Data Select Equipment and Batch Size Select Homomixer Speed Measure Batch Parameter Changes with Time (particle size, viscosity,etc.)
Develop Energy Curve (Based on Several Speeds) Result: Known energy capabilities of different Brands of Equipment at Company’s Plant sites and at Subcontractors
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Reference (Equivalent Energy Input)
RPM
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Kettle B Reference
Reference
Kettle A
RPM
30
1350
RPM
2400
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Scale Up Equivalent Mixing Energy HOMOMIXER SHAFT RPM Lee Tri-Mix
Greerco
50L/50kg
50L/50kg
Greerco 1200L/1200kg
Unimix 2000L/2000Kg
2000
1500
630
1025
3650
3060
1220
1740
4480
3580
1493
2100
5050
4137
5620
2420 2890
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Scale Up
Equivalent Mixing Energy HOMOMIXER SHAFT RPM Lee Tri-Mix
Greerco
Greerco
50L/50kg
50L/50kg
1200L/1200kg
2000L/2000Kg
2000
1500
630
1025
3650
3060
1220
1740
4480
3580
1493
2100
5050
4137
5620 32
Unimix
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Homogenizer Speed
Homogenizer Speed RPM
Pilot Lab
15
0
50
55
65
120
120
Time (Minutes)
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Scale Up
Equivalent Mixing Energy HOMOMIXER SHAFT RPM Lee Tri-Mix
Greerco
Greerco
50L/50kg
50L/50kg
1200L/1200kg
Unimix 2000L/2000Kg
3 2000
1500
630
1025
2 3650
3060
1220
1740
1 4480
3580
1493
2100
5050
4137
5620 34
2420 2890 Copying of this Information Prohibited without Permission
Pilot Lab
Homogenizer Work Input
Work Input
Manufacturing
15
55
120
Equivalent Energy Input 0
50
65
120
Time (Minutes)
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Pilot Lab
Homogenizer Speed
Homogenizer Speed RPM
Manufacturing
15
0
50
55
65
120
120
Time (Minutes)
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Scale Up Summary: Equivalent Cooling Time Match Cooling Curves of Plant Equipment Q = Uo x A x (delta T) Surface Area limits Cooling Capacity with increasing Batch Size Hold time Constant: Realistic Production Cycle time Controls crystallization growth rate Keeps Shear Energy Rate constant over the same temperature range
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Scale Up Summary: Equivalent High Shear Energy Match Shear Energy of Plant Equipment Hold Time Constant when applying High Shear Mixing: Based on equivalent mixing energy Select Homomixer Shaft speed
Maintain Macro-mixing to ensure batch uniformity Horse Power limits Mixing Blade Diameter and Speed as Batch Size Increases
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Scale Up Benefits of applying the 4 keys of Scale up
Smoother transition of Manufacturing Procedures from lab to plant
Fewer failures on First Production Batches Quick Production Start-up with less scrap/rework
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