Size reduction

Question 1

Size reduction is also known as

Answer 1

Comminution
Grinding
Milling

Question 2

What is size reduction

Answer 2

Mechanical process of reducing a solid into a smaller state of sub-division

Question 3

Need for size reduction

Answer 3

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

Question 4

Energy utilization in size reduction

Answer 4

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

Question 5

How size reduction occurs

Answer 5

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

Question 6

Hooke’s Law

Answer 6

F = kX

• F = Force needed to extend/compress spring by some amount
• k = Constant factor characteristic of spring
• X = Proportional to that force

Question 7

Particle size distribution throughout milling process

Answer 7

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

Question 8

Consideration in size reduction

Answer 8

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

Question 9

Size reduction mechanisms

Answer 9

1) Impact
2) Compression
3) Shear
- Particle-particle interaction
4) Attrition
- Arising from particles scraping against one another/a rough surface

Question 10

Wet grinding/milling - Advantages

Answer 10

1) Eliminate dust
2) Easier to handle material
3) Increase mill capacity
4) Less energy needed (more efficient)

Question 11

Wet grinding/milling - Disadvantages

Answer 11

1) Increase wear of grinding material
2) Not applicable to soluble material
3) May require drying

Question 12

Wet grinding/milling - Applications

Answer 12

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

Question 13

Types of mills

Answer 13

1) Roll mill
2) Hammer mill
3) Cone mill
4) Vibratory ball mill
5) Air jet mill
6) Fluid energy mill

Question 14

Roll mill - How it works

Answer 14

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

Question 15

Roll mill - Application

Answer 15

Used to mill:

1) Soft materials
2) Paste
3) Coarse crushing
4) Particulate solids

Question 16

Hammer mill - Components

Answer 16

1) Rasping screen

2) Impeller/Rotor

Question 17

Hammer mill - Types of impeller

Answer 17

1) Knife edge
2) Impact/Blunt edge
3) Bar rotor

Question 18

Hammer mill - Particle size produced

Answer 18

20 - 30 µm

Question 19

Hammer mill - Factors affecting particle size produced

Answer 19

1) Type of screen
2) Rotor speed
- Affects angle at which particles are pushed out of screen
- Higher rotor speed –> smaller particles

Question 20

Hammer mill - Advantages

Answer 20

1) Several models available, vertical & horizontal designs
2) Medium to high shear applications
3) Suitable for very hard materials
4) Blade & screens are interchangeable

Question 21

Hammer mill - Disadvantages

Answer 21

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

Question 22

Hammer mill - Applications

Answer 22

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

Question 23

Cone mill - Operating principles

Answer 23

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

Question 24

Cone mill - Applications

Answer 24

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)

Question 25

Vibratory ball mill - How it works

Answer 25

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

Question 26

Vibratory ball mill –> Equipment

Answer 26

Balls

• Made of ceramics/stainless steel
• Very heavy & dense
• Ball size & density affects milling

Question 27

Vibratory ball mill - Particles formed

Answer 27

Very fine particles (micronizing mill)

Question 28

Vibratory ball mill - Application

Answer 28

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)

Question 29

Air jet mill - How it works

Answer 29

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

Question 30

Air jet mill - Particles formed

Answer 30

Up to micron sizes (< 10 µm) (micronizing mill)

Question 31

Air jet mill - Applications

Answer 31

1) Used for milling of very hard materials

Question 32

Air jet mill - Advantages

Answer 32

1) Low likelihood of metal contaminating particles

- Milling by particle-particle impacts –> no abrading of surfaces of mill

Question 33

Fluid energy mill - How it works

Answer 33

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

Question 34

Fluid energy mill - Particles formed

Answer 34

Up to micron sizes (< 10µm) (micronizing mill)

Question 35

Fluid energy mill - Application

Answer 35

1) Used to grind very hard materials