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SoM 2 sim > Particle Size Reduction, Mixing, Granulation and Drying > Flashcards

Particle Size Reduction, Mixing, Granulation and Drying Flashcards

1
Q

Define toughness

A

It is a measure of a material’s resistance to fracture.

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2
Q

What is the difference between elastic deformation and plastic deformation?

A

Elastic deformation is reversible once stress is removed, unlike plastic deformation which is permanent.

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3
Q

What is an example of crack propagation?

A

Fracture of a birttle material under stress.

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4
Q

Why is particle size reduction not an efficient process?

A

As only a small portion of the energy provided to the system is used to reduce particle size; most of the energy is lost through heat, friction, vibration, crack initiation or elastic/plastic deformation.

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5
Q

Give an example of materials that become brittle when cooled at low enough temperatures (often well below freezing)

A

Rubber and other waxy or sticky materials.

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6
Q

What are the 4 different types of mechanical stress that can be used to break down particles?

A
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7
Q

What is the size range, principle and method when using cutting mills method?

A

Method:Cutting

Size range: 500-50,000 microns

Principle:Particles are fractured between two sets of knives. A stationary set on the mill casing and set attached to the rotor.

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8
Q

What is the size range, principle and method when using roller mills method?

A

Method: Compression

Size range: 1,000-100,000 microns

Principle: Powder is compressed between two rotating cylinders

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9
Q

What is the size range, principle and method when using hammer mills method?

A

Method: Impact

Size range: <100 -10,000 microns

Principle: Particle size is reduced upon impact driven by 4 (or more) rotating hammers

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10
Q

What is the size range, principle and method when using Ball mill method?

A

Method: Impact & Attrition

Size range: 1 to just above 100 microns

Principle: A rotating cylinder filled to 30-50% with balls. The mill can be filled with a variety of ball sizes to improve the size reduction process.

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11
Q

What is the size range, principle and method when using Fluid energy mill method?

A

Method: Impact & Attrition

Size range: 1 - 50,000 microns

Principle: Air is injected at a high-pressure, creating turbulence which will lead particles to collide with other particles and with the wall of the mill.

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12
Q

What do you need to consider when selecting to produce very coarse powders ( > 1000 microns)?

A
  • Cutting methods for tough/soft particles
  • Roller or hammer mill for harder particles
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13
Q

What do you need to consider when selecting to produce coarse powders ( 50-1000 microns) ?

A
  • Soft/tough materials: size reduction performed under liquid nitrogen
  • Cutting still possible for soft materials, under liquid nitrogen
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14
Q

What do you need to consider when selecting to produce fine powders ( >50 microns) ?

A
  • Ball or vibration mill (under liquid nitrogen for soft materials)
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15
Q

Size seperation can be used using which methods?

A
  1. Sieving methods with or without aid.
  • Agitation
  • Brushing
  • Centrifugation
  1. Sedimentation
    * Based on a similar principle as sedimentation-based particle size analysis
  2. Elutration
    * Seperation under an fluid layer moving in an upwards direction
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16
Q

A cutter mill can be used to produce fine particles from a hard material

TRUE or FALSE

A

FALSE

They are suitable for size reduction of soft to medium-hard fibrous and tough materials, plastics and heterogeneous mixtures.

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17
Q

What is meant by the neutral mixture category?

A
  • Mixing is NOT spontaneous
  • Demixing is NOT spontaneous
  • Energy input will be required for the powders to mix or demix
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18
Q

What is positive mixing?

A
  • Simplest situation.
  • Spontaneous mixing, energy only required if time constraint. Between liquids, gases (air).
  • You only input energy if you want to speed up the process
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19
Q

What is Neutral mixture?

A
  • Non-spontaneous mixing and non-spontaneous demixing.
  • Energy input would be required to start the mixing process, unless we disturb the mix it will not demix.
  • Examples: Pastes, powders.
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20
Q

What is negative mixing?

A
  • Energy input is required.
  • Spontaneous demixing. Fast or slow.
  • e.g, emulsion that doesnt contain a stabuliser.
  • input energy required to make the oil and water mix.
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21
Q

What are the 2 mechanisms for mixing?

A

Small scale and Large scale mixing

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22
Q

What is the equipment needed to peform small scale mixing?

A
  • Mortar and pestle
  • Glass tile
  • Closed container
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23
Q

How is large scale mixing achieved?

A
  • Convection
  • Shear
  • Diffusion
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24
Q

What is convection mixing?

A

When the powder is moved in bulk from one part of the powder to another

25
Q

What are the pros and cons of Ribbon mixers?

A

Pros:

  • Ability to mix powders with poor flow properties
  • Lower risk of segregation(demixing) vs tumble mixer

Cons:

  • Dead spots in hard-to-reach corners are hard to avoid
26
Q

What are ribbon mixers?

A

These mixers achieve macromixing, which is large scale mixing under stirring

27
Q

What is shear mixing?

A

In shear mixing, layers of bulk powder are moved during the mixing process.

The mixing achieved is semi-micromixing, an intermediate between the macromixing of agitators and micromixing of diffusion methods.

28
Q

What are the pros and cons of shear mixing?

A

Pros

  • Good for free flowing powders

Cons

  • Lower efficieny for cohesive powders with poor flow
  • Risk of segragation/demixing
29
Q

What is the main mechanism for Tumbling agitators?

A

Shear mixing

30
Q

Pros and cons High-shear mixer granulators?

A

Pros

  • Allows mixing and granulation in the same equipment

Cons

  • Not the best choice for mixing lubricant into powders
  • Potentially issues with very firable materials
31
Q

What is diffusion mixing?

A

In diffusion mixing, individual particles are moved during the mixing process. This allows micromixing as particles rearrange as they mix.

32
Q

Pros and cons of diffusion mixing?

A

Pros

  • Allows mixing and granulation in the same bowl
  • True random mix

Cons

  • Low mxing rate
33
Q

What is demixing?

A

Demixing is the seperation of a powder blend.

34
Q

What is the easiest way to avoid demixing?

A

Since powder blends are neutral mixtures, the easiest way to avoid demixing is by limiting handling of the powder bed.

35
Q

What casues demixing?

A

Demixing is more likely in powders with a wide distribution of;

Sizes

Densities

  • less likely for pharmaceutical preparations except in fluidised beds

Shapes

  • spherical shape = better flow = better mixing BUT also = higher risk of demixing
  • irregular shape = more cohesive = lower risk of demixing
  • shape may vary as the powder is process/handled.
36
Q

What causes the seperation of blend components?

A
  • Having a wide size distribution
  • Variation of shape
  • Difference in density
  • Difference in surface properties
37
Q

What is Percolation?

A

Accumulation of small particles at the bottom of a powder bed

Increased risk if the powder is disturbed

Can be potentiated if the small particles also have a higher density

38
Q

What is trajectory segregation?

A

Accumulation of larger particles at the edge of a powder cone (i.e. powder heap)

Results for a difference in kinetic energy of larger vs. small particles

Can overlap with percolation

Can also occur for particles of similar sizes but different densities

39
Q

What is dusting out?

A

Small particles are lifted and settle at the top of the powder bed

It’s also called: fluidisation segregation, eluthation segregation

40
Q

How do adhesion and cohesion forces effect granulation?

A

Forms thin layer

  • Increases attrctive forces
  • Increased contact area
41
Q

What is the benefit of using viscous adhesive solutions as a granulation fluid?

A

They have relatively stronger bonds

e.g. Starch mucilage as granulation fluid

42
Q

In wet granulation, what are the stages as you add granulation fluid?

A

NB: In most cases you dont want to reach the suspension stage, as this means too much of the granulation fluid has been added.

Having the powder particle in suspension is only used when used for spray-drying to produce granules.

Drying creates more permenant bridges .

43
Q

How are solid bridges formed during drying?

A

Crystallisation of solutes

  • Dissolution in granulation fluid
  • Re-crystalisation upon drying
  • Crytsal size will depend on drying rate

Hardening Binders

  • Use of biners in wet granulation: hardening/crystallisation during drying

Partial melting:

  • Melting of a solid under pressure
    • Dry granulation
    • Binding upon re-crystallisation
44
Q

If no solid or liquid bridegs can’t be formed, what other forces can be used?

A

Electrostatic forces

  • Realtively weak interaction

Van der Waals

  • Stronger than electrostatic
  • Important for granule strength during dry granulation
  • Stronger at short interparticular distances
45
Q

Describe the three steps of granule formation

A
  • nucleation: adhesion from liquid bridges (pendular or capillary state)
  • transition: nuclei growth (pendular bridges, nuclear aggregation, wide size distribution)
  • ball growth: granule growth
46
Q

What are the four types of ball growth?

A
  • coalescence: fusion of two granules
  • breakage: two granules in contact, weaker one breaks and adsorbed onto other one
  • abrasion transfer: friction between two granules, some absorb on surface
  • layering: second powder blend absorbed onto surface of granule (spheronisation - controlled release granule)
47
Q

What is total moisture content the sum of?

A
  • free moisture content
  • equilibrium moisture content (harder to remove)
48
Q

What makes drying efficient?

A
  • large SA
  • efficient heat trasnfer
  • efficient mass transfer
  • efficient vapour removal
49
Q

What do we need to consider for method selection?

A
  • properties of powder
  • sensitivity to heat
  • physical properties
  • nature of liquid
  • amount of powder to dry
  • need for sterilitiy
  • source of heat
50
Q

What are the main drying mechanisms?

A
  • convection: bulk movement of heated air
  • conduction: heating by contact with hot surface
  • radiation: heat transfer by radiation
  • spray drying: drying of liquid into a solid particle
  • freeze drying: drying through sublimation
51
Q

What are pros and cons of convection drying?

A

pros

  • high drying rates
  • shorter heat exposure
  • constant rate
  • uniform
  • attrition

cons:

  • dust production
  • segregation
  • risk of explosion
52
Q

Describe conduction drying

A
  • used on substances which are hygroscopic and heat senssiitve
  • vacuum oven
    • drying at lower temp
    • reduction in pressure reduces temp required
53
Q

What are pros and cons of radiation drying?

A

pros:

  • rapid drying at lower temp
  • high thermal efficiency
  • reduced solute migration

cons:

  • for smaller batches
  • hazardous radiation
54
Q

What are pros and cons of spray drying?

A

pros:

  • efficient mass transfer
  • rapid evaporation
  • improved flow

cons:

  • cost
  • low thermal efficiency
55
Q

What is spray drying used for?

A
  • thermolabile compounds
  • dry powder inhalers - keeps taste, flavour and colour
56
Q

What are three drying issues?

A
  • solute migration (towards surface and any solid dissolved within it moves too)
    • surface populated by solid
  • intergranular migration
    • occurs if short intergranular distance such as tray drying
  • intragranular migration
    • solute moving to surface of granule
57
Q

What are three consequences of drying issues?

A
  • solute migration causes
    • uniformity of content issues
    • loss of drug to granule surface
  • mottling in coloured tablets
    • intragranular migration of colour
    • high colour density on surface
  • migration of soluble binder
    • surface enriched with binder = harder granules
58
Q

How can you prevent solute migration?

A
  • add absorbent powder - starch, mycrocrystalline cellulose
    • will increase affinity of solute for the granule, rather than granulation fluid
  • control solubility
    • limit affinity for the fluid
  • use viscous granulation fluids
    • diffusion rate reduced
  • limit initial moisture content
  • control granule size
    • larger = more issues

SoM 2 sim (21 decks)

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