W21 Powder technology Flashcards
two systems/powders
- monocrystalline
- systems with defined habits/shaps - polycrystalline
- systems composed of aggregates of smaller particles (microcrystals)
Particle size
Coarse >350um
Medium 100-350um
Fine 50-100
Very fine 10-50
Micronised 10 >
Coarse, medium, fine - tablet/ capsule
very fine - suspension
Micronised - aerosol
ideal vs real powder
ideal: mono-sized / mono-dispersed
real: poly-dispersed
how to measure size of non-spherical particles
aspect ratio = length / width (breath)
how to change roughness of particle
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
who has high cohesion
small particles = high contact area
tangent of angle in angle of repose represent
coefficient of internal friction
tapped density
more (. ) powder = more (. ) = (. ) difference in (. ) and tapped density
cohesive
air trapped
larger
bulk
two formulas to represent tapped density
- Hausner ratio
volume (i) /volume (f) = density (f)/density (i)
- good flow: < 1.2
- bad flow: >1.4 - Carr’s compressibility index
(tapped density - bulk density) / tapped density x 100
- good flow: 5-15
- bad flow: 25 <
different mechanisms of mixing
- convective mixing
- move large portion of powder from one area to another
- no mvm within that individual portion - Shear mixing
- one layer of powder flows over another layer - Diffusive mixing
- particles to tumble over each other
what is a good mix
- Random mix
- probability of finding a type of particle is proportional to the number of them in overall mix - Ordered mix - only for aerosol formulation, not solid dose forms
- when small drug particles stick on larger excipient carrier particles
Types of mixers
- Tumble mixer / roller mixer
- Agitator mixers
Tumble mixer / roller mixer details
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
Agitator mixers details
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
considerations for mixing
- endpoint detection
- mixing speeds
- mixing time
- sampling
- blade configuration - if agitator mixer
- Powder quantities
- particle morphology
de-mixing = segregation
- happens when
- occurs during
- if mixing process is too long
- during moving between operations
- during hopper during further processing
mechanism of segregation
- percolation - particle size differences
- trajectory differences - size/momentum difference
Compression effects
- consider two criterias
- brittle fracture
- when interparticulate bonding between 2 mixes isn’t good and break easily
- increase total particulate SA
- avoided by adding binders - Plastic defoormation
- deformation of tablets
- solution: compatibility improved by adding binders
importance of particles/powders in manufacture (4)
- for even distribution
- for even flow
- compression behaviour
- biological behaviour
importance of powder flow
- powders must be moved between various operations = flowability impt
- reproducibility
- efficient powder flow = homogeneous distribution of API / excipients = uniform dosage
what affects cohesion
- VDW
- surface tension forces between adsorbed liquid layers (air moisture can affect cohesion)
- electrostatic attraction
- contact area = smaller particles show more cohesion and aggregate
method of angle of repose test
- pour powder through funnel
- measure angle it makes to horizontal surface
- multiple angles = avalanche represent
- tangent of angle represent
- uneven flow. collapse = poor flow
- coefficient of internal friction
How to define a good mix (scale of scrutiny)
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
- Sample size that’s close to unit dose of tablet/capsule
how do you get well distributed mix= same amount in each tablet
- use appropriate mixing process & equipment to maximise even drug distribution
- avoid segregation during mixing
- micronise drug (but not to the extent it becomes cohesive)
- particle shape affects
- all sperical particles (both drug and excipient) = good
- mixed morphology particles = poor mix
compressing a powder mix
- even dose = mix
- flow of powder into equipment = powder flow
- drug dissolving from solid dosage form = size of tablet
- compression = deformation
must be appropriate
