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

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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

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SLIDE 1

Process Scale-down Considerations during Formula Development

Michael Kalkstein 09 March 2017

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SLIDE 2

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

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SLIDE 3

Topics

  • Equipment

− Propeller mixers and blades − Homogenizers − Sweep mixers − Utilities

  • Process

− Ingredient − Formula − Documentation − Magnitude of scale − Plant operation practices

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SLIDE 4

Propeller Mixers

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SLIDE 5
  • Functions:

− Batch mixing (turnover) − Ingredient incorporation − Assist in heat transfer

  • Shear: Low (typically)
  • Types:

− Pneumatic vs Electric − Direct vs Gear Drive

PROPELLER MIXERS

Basics

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SLIDE 6

PROPELLER MIXERS

Setup

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  • Cylindrical vessel (Z/T ≥ 1)

− Angular (A)

  • No angle (parallel

to vessel wall)

− Horizontal (H)

  • Slightly off-center

to center

− Vertical (V)

  • 1.0D to 2.0D

from vessel bottom

Z T V H D

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SLIDE 7

PROPELLER MIXERS

Setup

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  • Hemispherical vessel (Z/T ≥ 1)

− Angular (A)

  • 10-20 degrees

from vessel wall

− Horizontal (H)

  • Slightly off-center

to center towards mixer motor

− Vertical (V)

  • 1.0D to 2.0D

from vessel bottom

Z T A V H

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SLIDE 8

A-310 (hydrofoil)

  • Turnover / powder

wetting

  • Very good pumping

(NQ ~ 0.64)

  • Low to high

viscosity fluids

  • Speeds ≤ 1800 rpm
  • High power needs

(NP ~ 0.62)

A-100 (marine)

8

PROPELLER MIXERS

Blade Selection

  • Turnover
  • Good pumping

(NQ ~ 0.56)

  • Low to medium

viscosity fluids

  • Speeds ≤ 1800 rpm
  • Low power needs

(NP ~ 0.30)

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SLIDE 9
  • Powder dispersion

(medium shear)

  • Poor pumping

(NQ ~ 0.32)

  • Low viscosity fluids
  • Speeds = 4000+ rpm
  • Medium power needs

(NP ~ 0.45)

R-500 (cowles)

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PROPELLER MIXERS

Blade Selection

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SLIDE 10
  • Direct drive mixer (lower viscosity):

− Minimum: DMIN = T / 6 Maximum: DMAX = 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)

PROPELLER MIXERS

Blade Sizing

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SLIDE 11
  • 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”

PROPELLER MIXERS

Blade Sizing

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SLIDE 12

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:

− 1.0 – “square” − 1.5 – “super”

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D Height

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SLIDE 13
  • Designed for a specific direction of

rotation, typically clockwise

  • Check markings on mixer hub

PROPELLER MIXERS

Blade Setup

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SLIDE 14

PROPELLER MIXERS

Vortex

  • A region in a fluid where flow is

rotating on a (vertical) axis

  • Don’t fear the vortex – use to

advantage for powder wetting!

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Heavy

moderate to heavy aeration

Moderate

slight to moderate aeration

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SLIDE 15
  • Overview, Left, Right

PROPELLER MIXERS

Video Demonstration

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SLIDE 16

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

  • peration

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SLIDE 17

PROPELLER MIXERS

Batch Turnover

  • Can be theoretically calculated with

limiting assumptions (water):

  • T

= mixing time [min] NQ = mixing blade flow number N = mixing speed [min-1] D = mixing blade diameter [in] 61 = unit conversion factor [in3 / L] V = batch volume [L]

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SLIDE 18

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

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SLIDE 19

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

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SLIDE 20

Homogenizers

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SLIDE 21

HOMOGENIZERS

Basics

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  • 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

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SLIDE 22

HOMOGENIZERS

Design

  • Rotor: Rotating center disc
  • Stator: Stationary outer disc
  • Shear Gap: Space between rotor and

stator

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SLIDE 23

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

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SLIDE 24

HOMOGENIZERS

Shear Study

“Coarse” General Purpose Disintegrating Stator

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“Medium” Square Hole High Shear Stator “Fine” Emulsor Stator

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SLIDE 25

HOMOGENIZERS

Shear Study

  • Shear Curves

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SLIDE 26

Sweep Mixers

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SLIDE 27

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

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SLIDE 28

Utilities

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SLIDE 29

UTILITIES

Heating

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  • Water bath / hot plate vs saturated

steam

  • Impact on ingredients?

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

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SLIDE 30

UTILITIES

Cooling

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  • 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

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SLIDE 31

Process

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SLIDE 32

PROCESS

Ingredient Considerations

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  • Chemistry
  • Functionality
  • Incompatibilities
  • Sensitivities

− Shear − Temperature − pH

  • Incorporation methods
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SLIDE 33

PROCESS

Ingredient Considerations

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  • Physical Properties

− Melt point − Flash point − Boiling point under vacuum

  • Safety
  • Storage and handling
  • Supply form and quantity
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SLIDE 34

PROCESS

Formula Considerations

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  • Sensitivities

− Shear

  • In-process
  • Discharge / filtration
  • Filling

− Utility temperatures − Cooling rate

  • Physical property data

− Viscosity at discharge − Rheology − Specific Gravity

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SLIDE 35

PROCESS

Documentation

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  • What

− Setup − Parameters − Observations − Test results

  • Why

− Scale-up − Trouble-shooting − Historical / future development − Legal

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SLIDE 36

PROCESS

Magnitude of Scale

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  • Ingredient quantity

− Solubility − Chemical interactions − Addition rate (“sprinkle”)

  • Mixing times (indirect scaling)
  • Metering rate (direct scaling)
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SLIDE 37

PROCESS

Plant Operations Practices

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  • 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

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SLIDE 38

PROCESS

Plant Operations Practices

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  • Control system capabilities
  • Bulk storage methods
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SLIDE 39

CLOSING

Recommendations

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  • Go to “Gemba”
  • Communicate and collaborate
  • Keep the end in mind.

Manufacturability is a critical component to the success of a product!

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SLIDE 40

Thank You

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SLIDE 41
  • Slide 5

− Picture: http://www.spxflow.com/en/lightnin/pd-mp-sanstar-sanitary-mixer-stainless-steel-ecl/

  • Slide 8

− A-100 Picture: http://www.spxflow.com/en/lightnin/pd-mp-axial-flow-impeller-a100/ − A-100 NQ (1.5 pitch): Worst-case value derived from Pumping Capacity Table – (Lightnin) Mixing Equipment

  • Co. Sales Data Book, Section 34, Page 5.10, 8-1-62

− A-100 NP (1.5 pitch): http://www.postmixing.com/mixing%20forum/impellers/pr.htm − A-310 Picture: http://www.spxflow.com/en/lightnin/pd-mp-axial-flow-impeller-a310-a510/ − A-310 NQ (1.5 pitch): http://www.postmixing.com/mixing%20forum/impellers/a310.htm − A-310 NP (1.5 pitch): http://www.postmixing.com/mixing%20forum/impellers/a310.htm

  • Slide 9

− R-500 Picture: http://www.spxflow.com/en/lightnin/pd-radial-flow-impeller-r500/ − R-500 NQ: http://www.postmixing.com/mixing%20forum/impellers/impellers.htm − R-500 NP: http://www.postmixing.com/mixing%20forum/impellers/impellers.htm

  • Slide 13

− Diagram: Lightnin Mixer Manual (2012), Figure 3 – Impeller Orientation

  • Slide 15

− Pictures & Videos: Proprietary source; For example purposes only – equipment performance varies by setup and application

  • Slide 19

− Video: Proprietary source; For example purposes only – equipment performance varies by setup and application

  • Slide 21

− Picture: http://www.ikaprocess.com/Products/Batch-dispersers-dispersing-machine-cph-13/ULTRA-TURRAX- UTS-csb-UTS/

Sources

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SLIDE 42
  • Slide 22

− Picture: http://www.ika.com/ika/pdf/flyer-catalog/Disperser_Brochure_EN_USD_IWW_screen.pdf (Page 8)

  • Slide 24

− Disintegrating Stator Picture: http://www.silverson.com/us/products/laboratory-mixers/workheads − High Shear Stator Picture: http://www.silverson.com/us/products/laboratory-mixers/workheads − Emulsor Stator Picture: http://www.silverson.com/us/products/laboratory-mixers/workheads

  • Slide 25

− Shear Curves: Proprietary source; For example purposes only – equipment performance varies by setup and application

  • Slide 27

− Picture: http://www.hockmeyer.com/products/high-viscosity-mixers/multi-shaft-blades/helical-blade- detail.html

  • Slide 29

− Table: http://www.engineeringtoolbox.com/saturated-steam-properties-d_273.html

PROPELLER MIXERS

Sources

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SLIDE 43

Additional Resources

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  • SCC Course: Scale-up and Processing Cosmetic Formulations
  • Book: Harry’s Cosmeticology (Chapter 35)
  • Websites:

− Lightnin: http://www.spxflow.com/en/lightnin/ (Products → Mixers, Impellers) − Brawn: http://www.hockmeyer.com/ (Mixing Knowledge Base) − Post Mixing: http://www.postmixing.com/ (Mixing Forum) − Silverson: http://www.silverson.com/ (Products, Process, Resource Library) − Ross: http://www.highshearmixers.com/ (Processes, Articles, Literature) − Hockmeyer: http://www.hockmeyer.com/ (Technical Center → Publications)

These are just a few website options. Many equipment manufacturers and mixing consultants post useful information and videos on their sites. Try starting with searches based on “mixer/ing”, “homogenizer” or “disperser”.