Particle Engineering: Milling/Agglomeration

Particle Engineering

Aims To introduce the principles and operation of milling (comminution) and agglomeration, as a size reduction/enlargement unit operation. Learning Objectives To describe unit operations; crushers, grinding mills, roller mills, impact jets, cutting mills and wet milling, for particle size reduction. To use crushing laws in the context of particle size reduction operation. To understand agglomeration principles.

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Topic: Milling and Agglomeration

Theory Breakage Mechanism Stability of breakage mechanism Crushing Laws Unit Operation Crushers Grinding mills Roller mils Impact jets Cutting mills Wet milling Agglomeration

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Particle size reduction (comminution)

One of the four main forms of mechanical processing (agglomeration, segregation and mixing) Commonly referred to as milling Particle size reduction through mechanical fracture, either particle-surface or particle-particle Size reduction to sub-micron particles, particularly in inhaled pharmaceuticals is known as micronisation.

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Particle size reduction

Energy intensive process (~1% of World Annual Electricity Consumption) Particulate products contribute $1 trillion annually to the US economy Regulatory Submission Specification Requirements (FDA, MHRA etc.) Particle size can affect pharmaceuticals: Flow Processing Content Uniformity Dissolution Rate and Profile Bioavailability

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Particle size reduction

Reactions increased rate as surface area is increased (directly proportional). Flow may be impeded due to increase in resistance to flow in a bed of small particles. Leaching increased in rate due to surface area and also distance liquid needs to travel. Drying increased in rate due to surface area and diffusivity from pores to surface.

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Particle size reduction

- crushing - grinding - milling - pulverising - micronising

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Particle size reduction

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Particle size reduction

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Existing Methods
Particle Engineering (Crystallisation seeding, nucleation, growth, harvest) Ultrasonics e.g. SAX from Prosonix Supercritical fluids e.g. CO2 processes from Nektar Therapeutics Proprietary wet milling e.g. Nanocrystal from Elan High shear dry and wet milling

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Particle size reduction

Size reduction due to particle fracture as a result of applying stress to the system Elastic and plastic deformation Dislocations (Edge and Screw) Slip systems (Planes, Direction) Fracture mechanism Brittle fracture electronic bonding, crystal structure, degree of order Crack initiation, propagation

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Mechanisms of particle breakage:

-Impact Particle concussion by a single rigid force. -Compaction Particle disintegration by two rigid force. -Shear Produced by a fluid or by a particle-particle interaction. -Attrition Arising from particles scraping against one another or against a rigid surface.

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Mechanisms of particle breakage:

- Impact - Compaction - Shear - Attrition Particle vs. particle Particle vs. hard surface Particle vs. fluid

Energy requirement for fracture:

- crack propagation (brittle vs. ductile materials) - surface fracture energy glass: 1-10 J/m2 polymers: 10-103 J/m2 metals: 103-105 J/m2

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Particle Breakage Mechanisms

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Impact particle-surface
Hammer and screen Air classifier Universal To control particle size: Rotational speed and direction Feed rate Plate configuration Air flow

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Impact particle-particle
Spiral jet Fluidised bed To control particle size: Classifier Air jet pressure Nozzle diameter Air flow

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Shear + Compression
Usually a combination Conical screen Oscillating granulation Rotary sieve mill To control particle size: Impellar Rotational speed Screen Spacing between impellar and screen

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Key Factors to Milling

Physicochemical and mechanical properties Initial size Requirements Temperature control Cleaning Safety Energy requirement (Theory Rittinger, Kick and Bond)

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Suitability of breakage mechanisms

Elastic materials (Hooks law - reversible deformation, time independence) Stress depends on contact force, not on velocity. Plastic materials (irreversible deformation, time independence) Stress almost independent of loading velocity, build-up of stresses => need repeated loading. Viscous materials (yield to stress, timedependent behaviour) Impact can be several times more efficient than slow compaction.

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Crushing laws
dE/dx = - k xm Eenergy; xparticle size; kmaterial-specific constant; mmechanism-dependent exponent Rittinger: energy per unit mass new surface area Kick: energy is proportional to size reduction ratio Bond: intermediate between Rittingers and Kicks Law.

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Example
Show that the energy requirements is given by: (a) Rittingers Law

(b) Kicks Law

1 1 E = C L L 1 2 L1 E = C ln L 2

(c) Bonds Law

1 1 E = 2C ln 1/2 1/2 L L1 2

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Crushing laws
Rittinger: Applicable mainly to part of process where new surface is being created and holds most accurately for fine grinding. Kick: More closely relates to the energy required to effect elastic deformation before fracture occurs, and is more accurate for coarse grinding where amount of surface created is less. Bond: An intermediate between Rittingers and Kicks laws.

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Example
A material is crushed from 50 mm to 10 mm with the consumption of energy 13.0 kW/kg. What would be the consumption of energy needed to crush the same material from 75 mm to 25 mm, assuming: a) Rittingers law, b) Kicks law?

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Equipment:
1. Crushers - jaw crushers (moving part against static wall) - gyratory crushers - roll crushers - impact & hammer crushers (highspeed)
Kirk-Othmer Encyclopedia of Chemical Technology

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Equipment:
2. Grinding Media Mills - milling balls or larger particles (autogenous mills) (a) tumbling (b) vibratory (c) planetary (d) agitated

Ullmanns Encyclopedia of Industrial Chemistry

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Motion patterns in a tumbling mill

(a) Cascading (b) cataracting (c) centrifugal

Ullmanns Encyclopedia of Industrial Chemistry

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Equipment:
3. Roller mills 4. Impact/Jet mills 5. Cutting mills (shredders) 6. Wet milling - disk attrition mills

Ullmanns Encyclopedia of Industrial Chemistry

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Ball Mill:
Factors affecting size:
1. Rate of feed 2. Properties of feed material 3. Weight of balls 4. Diameter of balls 5. Slope of the mill 6. Discharge freedom 7. Speed of rotation 8. Level of material in mill

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Energy Utilisation: 1. Elastic deformation prior to particle fracture 2. Inelastic deformation resulting in particle size reduction 3. Elastic distortion in equipment 4. Friction between particles, particles-wall 5. Noise, heat and vibration 6. Friction losses in plant itself.

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Particle Growth
Benefits: 1. Ease of particle handling
Fine particles tend to adhere (surface forces) forming conglomerates, ease to discharge as fines tend to stick to walls, reduced environmental and health related issues.

2. Flowability
Sometimes with addition of glidants

3. Reduced Electrostatic Charges

Agglomeration

Particle Engineering

Agitation

Compression

Drop Formation

Generally in the presence of the required proportion of a liquid phase and other binding agents

Materials pressed into a mould to give final shape, into a sheet, or through fixed diameter orifices and then broken down into smaller fragments

Solidification of droplets of solutions, slurries or melts

Tumbling Discs Drum

Roll Press Tablet Press Moulding Press Extrusion

Spray Drying Prilling

Mixer/Planetary Granulator Batch High Shear Continuous High Shear

Fluidised Bed Fluidised Bed Spouted Bed Wurster Coaters Agitated Fluidised Bed

Two types of processes causing agglomeration: Perikinetic attributed to Brownian movement, double layer repulsive force, van der Waals attractive force and electrostatic force. Orthokinetic where perikinetic process is supplemented by actin of eddy currents (eg stirred vessels, flow systems).

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Wet Granulation
1. Wetting and Nucleation Liquid binder is distributed onto the powder bed. Formation of initial agglomerates (nuclei granules).

2. Consolidation and Coalescence Mixing in the granulator promotes the collisions of nuclei granules leading to granule compaction and growth. 3. Attrition and Breakage Granules break due to wear, impact or compaction in the granulator.

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Wet Granulation
Wetting and Nucleation
Complete Wetting Distribution Coalescence

1) Particles

+ Binder Non Wetting

No Distribution Complete Wetting Immersion + 2) Particles Binder Non Wetting Solid Spreading

Limited Coalescence

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Wet Granulation
Consolidation and Coalescence
Critical viscous Stoke number:
h

1 h St v = 1 + ln e ha

d u0 u0 ha

where e is the coefficient of restitution (ratio of velocities after and before an impact), h is the thickness of liquid surface layer, and ha is the characteristic height of surface asperities. Stokes deformation number, Stv, is essentially a measure of the relative the kinetic energy absorbed plastically by the viscous binder during the impact

8mu 0 St v = 3 L d 2
where m is the particle mass, u0 is the impact velocity, L is the viscosity of the binder layer, and d is the particle diameter.

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Consolidation and Coalescence Three types of granule growth:

Non-inertial growth (Stv < Stv*)
All collisions lead to coalescence

Inertial growth (Stv = Stv*)

Particle coalescence or rebound is dependent on their size and mass. Process parameters and formulation properties determine the proportion of successful coalescence and may shift the system into either the non-inertia or coating regime.

Coating (Stv > Stv*)

Kinetic energy exceeds viscous dissipation in the liquid layer, resulting in no coalescence.

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Attrition and Breakage

Collisions between two surface wet, deformable granules:
Approach: Liquid layers merge at 2h, dissipating some kinetic energy of collision. Deformation: Granules begin to deform when the separation distance reduces to 2ha and velocity to u1. Remaining kinetic energy is dissipated by stored elastic energy and plastic deformation of the granules. Initial separation: Granules begin to rebound at a velocity of u2 as the stored elastic energy is released. Final separation: Viscous dissipation in the surface layer will retard granule separation. Granules are assumed to separate at a distance of 2h and granules rebound at a velocity of u3.
h u0 u0 u1 u1 u2 u2 u3 2h u3 ha

a)

b)

c)

d)

Increasing u0

Stv
Increasing Yd

Rebound

Increasing L

Type II Coalescence
Stv* = (1+1/e)ln(h/ha)

Type I Coalescence Stdef

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Iveson Model
Maximum granule pore saturation::

S max =

w S (1 min )

L min

where w is the mass ratio of liquid to solid, S is the solid particle density, L is the liquid density and min is the minimum porosity the formulation reaches for the particular set of operating conditions.
Crumb Slurry/Overwet Mass

0.1

Dry Freeflowing Powder

fS e d

t ,

Steady Growth
Increasing growth rate

f(Stv) Nucleation Only Induction m r o f e D s e k o t S

Decreasing induction time

1 Maximum Pore Saturation, Smax

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Granulation
Four key parameters; the particle surface roughness amplitude and correlation length, the equilibrium contact angle, and the relative droplet sizes affect the fractional surface coverage.
Stepanek and Rainiak, Langmuir 22, p917 (2006).

100

Cumulative Distribution, Q3 (%)

90 80 70 60 50 40 30 20 10 0 10

Ibuprofen:Mannitol - 0%:100% Ibuprofen:Mannitol - 25%:75% Ibuprofen:Mannitol - 50%:50% Ibuprofen:Mannitol - 75%:25%

Facet (120) (-120) (011)

Diidomethane 28.7 4.3 41.3 8.4 85.8 3.5

Water 44.6 2.8 41.3 2.4 18.6 2.3

Facets of Form I Mannitol Crystals

100 1000 Granule Size (m)

10000

R. Ho, Imperial College AstraZeneca PhD Studentship (S. Dilworth)

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Granulation
Schematic representation of selected wet agglomeration equipment.
a) Inclined Disc Granulator
Feed Binder Fines recirculation

b) Drum Granulator

Binder

Feed
Discharge

Fines recirculation

Discharge

c) High Shear Mixer

Binder Feed

d) Fluidised Bed Granulator

Binder Fines recirculation Feed Discharge

Discharge
Air

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Granulation
Schematic representation of selected wet agglomeration equipment.
e) Agitated Fluidised Bed Granulator
Feed Hot air Fines recirculation

g) Axial Screw Extruder

Feed + Binder

Discharge Air

Discharge

f) Roller Press (Briquetting)

Feed + Binder

h) Fluidised Spray Dryer

Binder Fines recirculation Feed Discharge

Air

Air

Discharge

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Size Enlargement Processes (a)Spray Drying

Mainly dependent on size of droplets, and design of nozzle. Droplet size is depended on liquid flowrate, viscosity, temperature.

(b)Prilling
relatively coarse droplets are allowed to fall in a narrow tall toward against an upward air flow.

(c) Fluidised Beds

atomised liquid is sprayed onto a fluidised bed, size largely depended on residence time. Rapid circulation leads to high interparticle interactions resulting in large particles (Spouted beds).

(d) Others - Drum and Pan Agglomerators, Pug Mills and Extruders, Elevated Temperatures

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Summary
Theory Breakage Mechanism Stability of breakage mechanism Unit Operation Crushers Grinding mills Roller mils Impact jets Cutting mills Wet milling Crushing Laws Mass Balances