Process Scale-down Considerations during Formula Development - PowerPoint PPT Presentation

Process Scale-down Considerations during Formula Development Michael Kalkstein 09 March 2017

Disclaimers  Basic process fundamentals based on professional knowledge and learnings  Many varied, multi-faceted approaches to successful process scaling  Consult with your fellow staff Engineers and Plant Operations personnel 2

Topics  Equipment − Propeller mixers and blades − Homogenizers − Sweep mixers − Utilities  Process − Ingredient − Formula − Documentation − Magnitude of scale − Plant operation practices 3

Propeller Mixers 4

PROPELLER MIXERS Basics  Functions: − Batch mixing (turnover) − Ingredient incorporation − Assist in heat transfer  Shear: Low (typically)  Types: − Pneumatic vs Electric − Direct vs Gear Drive 5

PROPELLER MIXERS Setup  Cylindrical vessel (Z/T ≥ 1) − Angular ( A )  No angle (parallel to vessel wall) − Horizontal ( H )  Slightly off-center to center Z − Vertical ( V ) V D  1.0 D to 2.0 D from vessel H bottom T 6

PROPELLER MIXERS Setup  Hemispherical vessel (Z/T ≥ 1) − Angular ( A )  10-20 degrees from vessel wall − Horizontal ( H )  Slightly off-center to center towards Z A mixer motor V − Vertical ( V )  1.0 D to 2.0 D H from vessel T bottom 7

PROPELLER MIXERS Blade Selection A-100 (marine) A-310 (hydrofoil) Turnover / powder Turnover   wetting Very good pumping Good pumping   (N Q ~ 0.64) (N Q ~ 0.56) Low to high Low to medium   viscosity fluids viscosity fluids Speeds ≤ 1800 rpm Speeds ≤ 1800 rpm   High power needs Low power needs   (N P ~ 0.62) (N P ~ 0.30) 8

PROPELLER MIXERS Blade Selection R-500 (cowles) Powder dispersion  (medium shear) Poor pumping  (N Q ~ 0.32) Low viscosity fluids  Speeds = 4000+ rpm  Medium power needs  (N P ~ 0.45) 9

PROPELLER MIXERS Blade Sizing  Direct drive mixer (lower viscosity): − Minimum: D MIN = T / 6 Maximum: D MAX = T / 4 where T = Vessel Diameter  Gear drive mixer (higher viscosity): − Minimum: d (min) = T / 4 Maximum: d (max) = T / 3 where T = Vessel Diameter  Disclaimer: Guidelines begin at large lab scale (≥ 10L) 10

PROPELLER MIXERS Blade Sizing  Why do sizing guidelines fall apart at small lab scale? − Surface area becomes so small that pumping capability is lost − Diameters become so small that multiple blades should be used  So what size should be used at small lab scale? − As small as possible − Standard sizes available: 1.5”, 2.0”, 2.7”, 3.1” 11

PROPELLER MIXERS Blade Pitch  Ratio of the height of the column of water displaced by 1 revolution of the blade…to the blade diameter (Height / D )  Common pitches: Height − 1.0 – “square” − 1.5 – “super” D 12

PROPELLER MIXERS Blade Setup  Designed for a specific direction of rotation, typically clockwise  Check markings on mixer hub 13

PROPELLER MIXERS Vortex  A region in a fluid where flow is rotating on a (vertical) axis Moderate Heavy slight to moderate aeration moderate to heavy aeration  Don’t fear the vortex – use to advantage for powder wetting! 14

PROPELLER MIXERS Video Demonstration  Overview, Left, Right 15

PROPELLER MIXERS Batch Turnover  The pumping of one vessel volume by a mixing element (BTO)  Generally used to describe good mixing in a vessel  Typically evaluated based on a single mixing element  Influenced by numerous factors − Fluid rheology − Mixing element configuration and operation 16

PROPELLER MIXERS Batch Turnover  Can be theoretically calculated with limiting assumptions (water): � � T = mixing time [min] N Q = mixing blade flow number N = mixing speed [min -1 ] D = mixing blade diameter [in] 61 = unit conversion factor [in 3 / L] V = batch volume [L] 17

PROPELLER MIXERS Batch Turnover Example  Lab scale: Mix 2 liter batch for 5 minutes at 500 rpm using: − 1.5” A-100 blade BTO’s = 45 − 2.0” A-100 blade BTO’s = 107 − 2.7” A-100 blade BTO’s = 262  Pilot scale: What would be the scaled- up mixing times for a 100 liter batch using a 4.5” A-100 blade operating at 1000 rpm? − 45 BTO’s Time = 4.6 min − 107 BTO’s Time = 11 min − 262 BTO’s Time = 27 min 18

PROPELLER MIXERS Batch Turnover Example  Lab scale: How much time should a 2 liter batch mix at 500 rpm to achieve 10 BTO’s using: − 1.5” A-100 blade Time = 1.1 min − 2.0” A-100 blade Time = 0.5 min − 2.7” A-100 blade Time = 0.2 min  Video 19

Homogenizers 20

HOMOGENIZERS Basics  Function: − Droplet size reduction − Solid ingredient dispersion − Batch mixing (turnover) − Not for grinding  Shear: moderate to high  Types: − Bottom vs top entry − Axial vs axial-radial flow 21

HOMOGENIZERS Design  Rotor: Rotating center disc  Stator: Stationary outer disc  Shear Gap: Space between rotor and stator 22

HOMOGENIZERS Design Factors  Generally…as shear capability increases, pumping capability decreases  Design factors to increase shear: − Stator slot shape: more rectangular − Stator slot width: narrower − Shear gap: narrower − Rotor face: more closed − Number of rotor/stator pairs: more pairs 23

HOMOGENIZERS Shear Study “Coarse” General Purpose Disintegrating Stator “Medium” Square Hole High Shear Stator “Fine” Emulsor Stator 24

HOMOGENIZERS Shear Study  Shear Curves 25

Sweep Mixers 26

SWEEP MIXERS Basics  Function − Scraped-surface heat exchange − Batch turnover  Counter-rotate to propeller mixer  Design-specific  Shear: Low  Types: Anchor vs Helical  Can dominate mixing pattern 27

Utilities 28

UTILITIES Heating  Water bath / hot plate vs saturated steam Saturated Steam Table Gauge Pressure Temperature [psi] [bar] [F] [C] 30 2.1 274 134 40 2.8 286 141 50 3.4 298 148 60 4.1 307 153 70 4.8 316 158  Impact on ingredients? 29

UTILITIES Cooling  Cooling is less controllable and much faster at lab scale  Target cooling rates at production scale: − >70C 1.5+ C/min − 55–70C 0.75 – 1.5 C/min − 35-55C 0.33 – 0.75 C/min − < 35C 0.25 – 0.33 C/min  Compensatory measures − Two-stage cooling − Insulation 30

Process 31

PROCESS Ingredient Considerations  Chemistry  Functionality  Incompatibilities  Sensitivities − Shear − Temperature − pH  Incorporation methods 32

PROCESS Ingredient Considerations  Physical Properties − Melt point − Flash point − Boiling point under vacuum  Safety  Storage and handling  Supply form and quantity 33

PROCESS Formula Considerations  Sensitivities − Shear  In-process  Discharge / filtration  Filling − Utility temperatures − Cooling rate  Physical property data − Viscosity at discharge − Rheology − Specific Gravity 34

PROCESS Documentation  What − Setup − Parameters − Observations − Test results  Why − Scale-up − Trouble-shooting − Historical / future development − Legal 35

PROCESS Magnitude of Scale  Ingredient quantity − Solubility − Chemical interactions − Addition rate (“sprinkle”)  Mixing times (indirect scaling)  Metering rate (direct scaling) 36

PROCESS Plant Operations Practices  Order of addition  Addition methods − Top addition vs induction  Premixes − Pre-disperse thickeners or powders − Dilute pH adjusters − Facilitate back-end additions  In-process quality checks − Always provide countermeasures 37

PROCESS Plant Operations Practices  Control system capabilities  Bulk storage methods 38

CLOSING Recommendations  Go to “Gemba”  Communicate and collaborate  Keep the end in mind. Manufacturability is a critical component to the success of a product! 39

Thank You 40