W21 Powder technology Flashcards

1
Q

two systems/powders

A
  1. monocrystalline
    - systems with defined habits/shaps
  2. polycrystalline
    - systems composed of aggregates of smaller particles (microcrystals)
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2
Q

Particle size

A

Coarse >350um
Medium 100-350um
Fine 50-100
Very fine 10-50
Micronised 10 >

Coarse, medium, fine - tablet/ capsule
very fine - suspension
Micronised - aerosol

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3
Q

ideal vs real powder

A

ideal: mono-sized / mono-dispersed
real: poly-dispersed

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4
Q

how to measure size of non-spherical particles

A

aspect ratio = length / width (breath)

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5
Q

how to change roughness of particle

A

by changing processing factors and control parameters
1)electrospraying: works by ionising solution of drug and creating spray of droplets. As solvents of droplets evaporate, particles with different morphology produced
2) can use different solvents

==> change morphology/size/surface roughness of particles, how they aggregate, how they flow

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6
Q

who has high cohesion

A

small particles = high contact area

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7
Q

tangent of angle in angle of repose represent

A

coefficient of internal friction

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8
Q

tapped density
more (. ) powder = more (. ) = (. ) difference in (. ) and tapped density

A

cohesive
air trapped
larger
bulk

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9
Q

two formulas to represent tapped density

A
  1. Hausner ratio
    volume (i) /volume (f) = density (f)/density (i)
    - good flow: < 1.2
    - bad flow: >1.4
  2. Carr’s compressibility index
    (tapped density - bulk density) / tapped density x 100
    - good flow: 5-15
    - bad flow: 25 <
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10
Q

different mechanisms of mixing

A
  1. convective mixing
    - move large portion of powder from one area to another
    - no mvm within that individual portion
  2. Shear mixing
    - one layer of powder flows over another layer
  3. Diffusive mixing
    - particles to tumble over each other
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11
Q

what is a good mix

A
  1. Random mix
    - probability of finding a type of particle is proportional to the number of them in overall mix
  2. Ordered mix - only for aerosol formulation, not solid dose forms
    - when small drug particles stick on larger excipient carrier particles
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12
Q

Types of mixers

A
  1. Tumble mixer / roller mixer
  2. Agitator mixers
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13
Q

Tumble mixer / roller mixer details

A

mix how
- diffusive, shear mixing
- runs at low speed

Good for
- free flowing powders
- direct compression mixtures for tableting
- lubrication

not good for
- very low drug loading
- mixing odd shaped particles
- wet granulation

Examples
1) V-blender
2) Double-cone mixer
- low shear, not good for very fine particles
- but good that it doesn’t have any dead spots mixisng, easy to clean
3) Rotating cube blender - corner가 있어서 안 쫗음

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14
Q

Agitator mixers details

A

characterstics
- for shear, convective mixing
- higher shear (quick)
- blade configuration is impt

GOod for
- more cohesive powders
- mixing odd-shapeed particles
- wet granulation
- very low drug loading

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15
Q

considerations for mixing

A
  1. endpoint detection
  2. mixing speeds
  3. mixing time
  4. sampling
  5. blade configuration - if agitator mixer
  6. Powder quantities
  7. particle morphology
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16
Q

de-mixing = segregation
- happens when
- occurs during

A
  • if mixing process is too long
  • during moving between operations
  • during hopper during further processing
17
Q

mechanism of segregation

A
  1. percolation - particle size differences
  2. trajectory differences - size/momentum difference
18
Q

Compression effects
- consider two criterias

A
  1. brittle fracture
    - when interparticulate bonding between 2 mixes isn’t good and break easily
    - increase total particulate SA
    - avoided by adding binders
  2. Plastic defoormation
    - deformation of tablets
    - solution: compatibility improved by adding binders
19
Q

importance of particles/powders in manufacture (4)

A
  1. for even distribution
  2. for even flow
  3. compression behaviour
  4. biological behaviour
20
Q

importance of powder flow

A
  1. powders must be moved between various operations = flowability impt
  2. reproducibility
    - efficient powder flow = homogeneous distribution of API / excipients = uniform dosage
21
Q

what affects cohesion

A
  1. VDW
  2. surface tension forces between adsorbed liquid layers (air moisture can affect cohesion)
  3. electrostatic attraction
  4. contact area = smaller particles show more cohesion and aggregate
22
Q

method of angle of repose test

A
  1. pour powder through funnel
  2. measure angle it makes to horizontal surface
23
Q
  • multiple angles = avalanche represent
  • tangent of angle represent
A
  • uneven flow. collapse = poor flow
  • coefficient of internal friction
24
Q

How to define a good mix (scale of scrutiny)

A

Aim = to get a good mix
- random mix
- ordered mix

Choosing sample size is impt
1. Large sample
- level of variation (precision) = larger sample gives less variation within mix
- drug loading (accuracy) = larger samples give drug loading that’s closwer to theoretical level

  1. Sample size that’s close to unit dose of tablet/capsule
25
Q

how do you get well distributed mix= same amount in each tablet

A
  1. use appropriate mixing process & equipment to maximise even drug distribution
  2. avoid segregation during mixing
  3. micronise drug (but not to the extent it becomes cohesive)
  4. particle shape affects
    - all sperical particles (both drug and excipient) = good
    - mixed morphology particles = poor mix
26
Q

compressing a powder mix

A
  1. even dose = mix
  2. flow of powder into equipment = powder flow
  3. drug dissolving from solid dosage form = size of tablet
  4. compression = deformation
    must be appropriate