Size reduction Flashcards
Size reduction is also known as
Comminution
Grinding
Milling
What is size reduction
Mechanical process of reducing a solid into a smaller state of sub-division
Need for size reduction
1) Increase surface area for reaction
2) Improve extraction of active principles
3) Improve dispersibility of drug in solution
4) Improve dissolution (increases surface area)
5) Allow better mixing/blending
6) Preliminary process in preparation of products
- Improve quality & performance of powders
- Assist in downstream processing
Energy utilization in size reduction
Only 1-2% of energy input used for size reduction Remaining energy lost as: 1) Elastic deformation 2) Plastic deformation without fracture 3) Deformation in initial cracks 4) Deformation of machine parts 5) Inter-particle friction 6) Particle-wall friction 7) Heat 8) Sound 9) Vibration
Small particles require more energy to break
How size reduction occurs
Particles fragment/abrade to give smaller particles
Breakage begins with small cracks:
1) Crack opening by tensile spreading at crack tip
2) Crack sliding by shear deformation parallel to crack direction
3) Crack tearing by shear deformation perpendicular to crack direction
Hooke’s Law
F = kX
- F = Force needed to extend/compress spring by some amount
- k = Constant factor characteristic of spring
- X = Proportional to that force
Particle size distribution throughout milling process
Start of milling:
Unimodal (single peak)
- Typical of product produced by crystallization
During milling:
Bimodal (2 peaks)
At end of milling:
Unimodal, with smaller size range
Consideration in size reduction
Properties of material:
1) Thermolability / Melting point
- Milling often results in heat –> if material has low MP / sensitive to heat –> may start melting/degrading during milling
- Milling should be carried out at least 10-20oC below MP
2) Flammability
- Introduction of nitrogen can reduce flammability
3) Deformation characteristics
- For size reduction/successful milling process to occur, supplied energy must be capable of exerting stress beyond the material’s break or fracture point
Fracture mechanics of particles
1) Hardness
2) Tensile strength
Mechanical: Type of equipment
1) Impact, shear, pressure
2) Material in contact with product
- Stainless steel 316 preferred in pharmaceutical industry
3) Temperature control
Size reduction mechanisms
1) Impact
2) Compression
3) Shear
- Particle-particle interaction
4) Attrition
- Arising from particles scraping against one another/a rough surface
Wet grinding/milling - Advantages
1) Eliminate dust
2) Easier to handle material
3) Increase mill capacity
4) Less energy needed (more efficient)
Wet grinding/milling - Disadvantages
1) Increase wear of grinding material
2) Not applicable to soluble material
3) May require drying
Wet grinding/milling - Applications
1) Formulation of carbonates, metallic materials, powder
2) Interest in using wet grinding to formulate nanoparticles
3) Less common in formulation of solid oral dosage forms
- Dry milling more common
Types of mills
1) Roll mill
2) Hammer mill
3) Cone mill
4) Vibratory ball mill
5) Air jet mill
6) Fluid energy mill
Roll mill - How it works
Material passed between rollers
Gap size between rollers determine extent of particle size reduction
- Gap size can be reduced up to ~50µm
Peripheral velocity & clearance between rolls can be varied
Roll mill - Application
Used to mill:
1) Soft materials
2) Paste
3) Coarse crushing
4) Particulate solids
Hammer mill - Components
1) Rasping screen
2) Impeller/Rotor
Hammer mill - Types of impeller
1) Knife edge
2) Impact/Blunt edge
3) Bar rotor
Hammer mill - Particle size produced
20 - 30 µm
Hammer mill - Factors affecting particle size produced
1) Type of screen
2) Rotor speed
- Affects angle at which particles are pushed out of screen
- Higher rotor speed –> smaller particles
Hammer mill - Advantages
1) Several models available, vertical & horizontal designs
2) Medium to high shear applications
3) Suitable for very hard materials
4) Blade & screens are interchangeable
Hammer mill - Disadvantages
1) Noisy & dusty
2) Sifting required
- Hammer milling results in particles of broad size distribution –> need sifting to achieve narrower size distribution
3) High volume air generated; Ventilation requirement
- A lot of air sucked in to cool down mill
4) Temperature rise due to friction
5) Screen selection & installation compelx; Not scalable
6) Belt slip common due to load
7) Cannot plug load
- Cannot fill with large amount of material at once
Hammer mill - Applications
1) Common in pharmaceutical industry
- Especially for crude milling
2) Commonly used in herbal/traditional medicine industry
- E.g. Milling of plant material, wood chips
3) Widely used
- Very economical
Cone mill - Operating principles
1) Infeed falls into conical screen chamber
2) Rotating impeller imparts vortex flow pattern to the infeed material
3) Centrifugal acceleration forces particulates to screen surface –> particulates are continuously delivered to the ‘Action Zone’ between screen & impeller, where particle size is reduced
4) Particles of appropriate size (≤ screen openings) will be discharged through the screen openings
Cone mill - Applications
1) Common in pharmaceutical industry
- Commonly used as mid-step of granulation process
2) Used to form particles of a certain size, rather than for large size reduction
- Forms coarser/larger particles (does not cause big size reduction)
Vibratory ball mill - How it works
Balls are vibrated at high frequency / cascaded –> breaks down particles between the balls
Vibration
- Extremely efficient BUT high temperature rise (may be overcome by having short process time/jacket to remove heat)
Cascading
- Long process time BUT less temperature rise
Vibratory ball mill –> Equipment
Balls
- Made of ceramics/stainless steel
- Very heavy & dense
- Ball size & density affects milling
Vibratory ball mill - Particles formed
Very fine particles (micronizing mill)
Vibratory ball mill - Application
1) Commonly used in pharmaceutics (but temperature rise may limit use in large scale milling)
2) Best used in wet grinding (but may still be used in dry grinding)
Air jet mill - How it works
1) Feeding of particles into mill chamber (controlled by screw feeder)
2) Air pressure nozzles located along sides of chamber release air into mill –> air pressure will cause particles to known into each other –> attrition/grinding occurs via particle-particle impacts
3) Separation of particles via classifier wheels
- Only particles of a certain size will be collected –> remaining larger particles will continue to be milled
- Speed of classifier wheel controls size of particles collected
Note: Good process control needed
Air jet mill - Particles formed
Up to micron sizes (< 10 µm) (micronizing mill)
Air jet mill - Applications
1) Used for milling of very hard materials
Air jet mill - Advantages
1) Low likelihood of metal contaminating particles
- Milling by particle-particle impacts –> no abrading of surfaces of mill
Fluid energy mill - How it works
1) Grinding air inlets located along side of milling chamber –> positioned such that accelerating air creates turbulence –> grinding via particle-particle impacts
2) Separation of particles via centrifugal separation
- Size of particles collected depends on speed of circulating air
Fluid energy mill - Particles formed
Up to micron sizes (< 10µm) (micronizing mill)
Fluid energy mill - Application
1) Used to grind very hard materials
