Size Reduction Flashcards

1
Q

What are some reasons for size reduction?

A
  1. Preliminary process in preparation of products,
  2. Allow better mixing or blending
  3. Enable rapid dissolution, especially solid dosage forms
  4. Increase S.A. for reaction
  5. Improve extraction of active principles
  6. Improve dispersibility in solution
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2
Q

Particles either fracture or abrade to give smaller particles. What is important in causing breakage of particles?

A

Crack initiation

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3
Q

From Hooke’s Law, what is required for a successful miling process?

A

Supplied energy exerts stress beyond material’s break or fracture point

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4
Q

Considerations in size reduction regarding properties of material

A

Size reduction generates heat hence consider:

  • Thermolability
  • Melting point
  • Flammability

Also consider: Deformation characteristics

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5
Q

Considerations in size reduction redgardin type of equipment

A
  • Impact/ shear/ pressure
  • Material in contact with product
  • Temperature control (e.g. via water jacket)
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6
Q

All size reduction equipment cause breakage by 4 basic mechanisms, which are:

A
  1. Impact: Single force (hammer)
  2. Compression: Two rigid forces (nut-cracker)
  3. Shear: Particle-to-particle interaction (scissors)
  4. Attrition: scraping against surface
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7
Q

What is wet grinding? WHat are its advantages and disadvantages?

A

Size reduction in liquid media, usually water

Advantages:

  • Eliminate dust
  • Easier to handle material
  • Uses less energy (higher efficiency)
  • Increase mill capacity

Disadvantages;

  • Grinding medium may become part of product
  • Unusable for soluble materials
  • May require drying of product
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8
Q

Roll mill is best for _______

A

Soft materials

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9
Q

Briefly describe how hammer mill works

A

Materials passed into rotating impellers which gets impacted and reduced in size. Small enough particles can pass through screen. It has less precise milling

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10
Q

Advantages and disadvantages of hammer mill

A

Advantages:

  • Different models and designs available
  • Can impart medium to high sheer
  • Blades and screens are interchangeable
  • Suitable for very hard materials

Disadvantages:

  • Temperature rise due to friction
  • Noisy, dusty
  • Cannot plug feed due to limited capacity (only gradual feed)
  • Belt slip common
  • High volume of air generated, rq ventilation
  • Complex screen selection and installation, and not scalable
  • Sifting required after milling
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11
Q

Compared to hammer mill, cone mills are….

A
  • More gentle

- Make coarser particles than hammer mill, hence suitable as mid-step in granulation

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12
Q

Describe the principle of operation of a cone mill

A
  • Feed into conical chamber
  • Impeller imparts vortex flow pattern to material
  • Centrifugal forces accelerate particles to screen surface
  • Particles with reduced size instantly discharge through screen openings
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13
Q

Describe Ball Mills. What are the two types of ball mills

A
  • Vibrate/rotate material with balls inside
  • Balls are dense and heavy, and when colliding, crushes particles in between them
  • With vibration: Very efficient, but best when materials and balls are wet

Two types: Vibratory and cascading

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14
Q

Advantages and disadvantages of ball mills

A

Advantages:
- Efficient, suitable for fine grinding

Disadvantages:
- For vibratory: Require cooling or short process time due to rapid temperature rise

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15
Q

Advantages and disadvantages of flud energy mill and air jet mills

A

Advantages:

  • Very fine grinding
  • Very efficient to micron size (<10 micron)
  • Can mill very hard materials

Disadvantages:
- Require good process control

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16
Q

What mechanism does fluid energy mill and air jet mill use to grind particles? How do size-select particles?

A

Mechanism: Particle-particle impacts (Shearing)

Size selection by:

  • Centrifugal separation (fluid energy)
  • Classifying wheel (air jet)
17
Q

Purpose of milling in pharm industries

A

Assist downstream processing such as blending and tableting by reducing particle size and improving performance and quality of powders

18
Q

Basic problem of particle size analysis

A

How to describe 3D object using just one number

19
Q

What is the equivalent sphere theory and what is this theory used for?

A
  • The use of 1D property of particle (sphere) as measurement to derive one unique number
  • Help gauge whether particle become bigger or smaller, according to changes in volume or weight properties
20
Q

What are some major sizing methods and the sizes they can measure?

A
  1. Scales - Micrometer: >5mm
  2. Sieves : >10µm
  3. Microscopy/image analysis: 5µm - 5mm
  4. Laser diffraction: 5µm - 5mm
  5. Laser scattering: 0.001µm - 5µm (usually for nanoparticles)
21
Q

Describe microscopy in analysing image size. What are some measurements that you can make to derive the size of particle?

A

Use microscopy and scale to carry out direct visual examination from captured 2D image

Measurements

  1. Martin’s diameter: max particle length as diameter
  2. Feret’s diameter: Distance between two adjacent line tangent to ends of particles (i.e. greatest distance possible between any two points laong boundary of particle)
  3. Minimum diameter
  • All measurements give different particle size
22
Q

Disadvantages of microscopy to analyse image size

A
  1. Operator dependent
  2. Danger of non-representation (miss one 10µm particle = miss thousand 1µm particles)
  3. Laborious and slow
  4. NBS recommend 10000 images for statistical validity
23
Q

Describe the usage of sieves in measuring particle size. What is it good for?

A
  • Pass material through size-selecting material like woven mesh, and measure time to take for particles to fall through sieve
  • Longer time = smaller size
  • Low-resolution method
  • Good for quality control (robust and easy to do)
24
Q

Describe electrozone sensing in measuring particle size

A
  • Disperse particles in electrolyte as suspension
  • Pass electric current
  • Measure size based on orifice obscuration, hwere resistance ≈ area ≈ size
25
Q

Advantages and Disadvantages of electrozone sensing to measure particle size

A

Advantage: Unaffected by optical properties, densities, colours and shapes of particles

Disadvantages:

  1. Require expensive calibration standards
  2. Unsuitable for large particles that sediment fast (dense materials)
  3. Unsuitable for porous particles
  4. Particles must be insoluble and non-conductive
  5. Only most suitable for 2-5µm
26
Q

Describe laser diffraction method in measuring particle size

A
  • Pass laser beam through particles
  • Laser beam diffracts, and angle of diffraction is measured
  • Higher angle of diffraction = smaller particle
27
Q

Advantages of laser diffraction in measuring particle size

A
  • Wide dynamic range, very flexible
  • Can measure dry powder, spray or particles in air/liquid
  • Non-destructive, non-intrusive
  • Volume of distribution, equal to weight distribution is generated where density is constant
  • rapid, high resolution and highly reproducible
  • No calibration with standard required
  • Performance easily verified
28
Q

Distinguish light scattering and laser diffraction in measuring particle size

A
  • Light scattering: measure light reflected (dynamic and quasi-elastic light scattering)
  • Laser diffraction: Measure light diffracted
29
Q

Describe light scattering in measuring particle size

A
  • Based on brownian motion, generally below 3µm
  • Speed of movement is inversely proportional to size
  • Photo-correlation spectroscopy can be obtained
  • The speed is detected by analysing time-dependency of light intensity fluctuations scattered from particles when they are illuminated

(Analogy: Shine car on faster vs slower car and measure time of light reflection)

30
Q

In terms of particle size distribution model, particles follow _____ distribution before milling, _____ distribution during milling and then back to _____ distribution after milling

A

Unimodal, Bimodal, Unimodal

Bimodal distribution during milling due to particles of different sizes

31
Q

Describe air jet sieve, and what is it good for. What kind of graph can you obtain?

A

For sieving fine powders <200µm which tend to agglomerate

  • Weighed material placed on sieve of certain aperture size
  • Air underneath mesh to break up particle
  • Particles smaller than aperture size passed through
  • Material remaining on sieve weighed
  • Process repeated with sieves of different aperture size
  • Cumulative graph of %weight oversize can be obtained
32
Q

What is Span in terms of particle size, and what is its formula? Where can we obtain span?

A

Span measures particle size distribution

Obtain from Cumulative weight% frequency against sieve equivalent diameter graph

Span = (D90 - D10)/D50
- D90/D10/D50 are diameter of sieves at cumulative W frequency of 90/10/50%

33
Q

From Cumulative weight% frequency against sieve equivalent diameter graph, what is D50?

A

Mass median diameter