W21 Powder technology

Question 1

two systems/powders

Answer 1

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

Question 2

Particle size

Answer 2

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

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

Question 3

ideal vs real powder

Answer 3

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

Question 4

how to measure size of non-spherical particles

Answer 4

aspect ratio = length / width (breath)

Question 5

how to change roughness of particle

Answer 5

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

Question 6

who has high cohesion

Answer 6

small particles = high contact area

Question 7

tangent of angle in angle of repose represent

Answer 7

coefficient of internal friction

Question 8

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

Answer 8

cohesive
air trapped
larger
bulk

Question 9

two formulas to represent tapped density

Answer 9

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 <

Question 10

different mechanisms of mixing

Answer 10

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

Question 11

what is a good mix

Answer 11

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

Question 12

Types of mixers

Answer 12

1. Tumble mixer / roller mixer
2. Agitator mixers

Question 13

Tumble mixer / roller mixer details

Answer 13

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

Question 14

Agitator mixers details

Answer 14

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

Question 15

considerations for mixing

Answer 15

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

Question 16

de-mixing = segregation
- happens when
- occurs during

Answer 16

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

Question 17

mechanism of segregation

Answer 17

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

Question 18

Compression effects
- consider two criterias

Answer 18

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

Question 19

importance of particles/powders in manufacture (4)

Answer 19

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

Question 20

importance of powder flow

Answer 20

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

Question 21

what affects cohesion

Answer 21

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

Question 22

method of angle of repose test

Answer 22

1. pour powder through funnel
2. measure angle it makes to horizontal surface

Question 23

• multiple angles = avalanche represent
• tangent of angle represent

Answer 23

• uneven flow. collapse = poor flow
• coefficient of internal friction

Question 24

How to define a good mix (scale of scrutiny)

Answer 24

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

2. Sample size that’s close to unit dose of tablet/capsule

Question 25

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

Answer 25

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

Question 26

compressing a powder mix

Answer 26

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