Engineering in Chemical and Pharmaceutical Processestresen.vscht.cz/.../11/2015-05-compaction-extrusion-spheronization.pdf · 2 Engineering in Chemical and Pharmaceutical Processes
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Engineering in Chemical and Pharmaceutical Processes
Particle sizing, Compaction, Extrusion
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compaction
„Dry-granulation“
Principle
Compressing the powder between two surfaces
Cohesive forces
van der Waals
mechanical interlocking
solid bridges (instantneous melting of the particles’ surfaces)
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compaction
Categories of materials
compactable
compactable with fragmentation
non-formable (glass, sand)
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Materials compactability
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Mechanism of compaction
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Energy analysis of compaction
Analysis of force required per displacement during compression and decompression
Energy = force * length
Energy = area under curve
EP = plastic deformation
EE = elastic deformation
EF = rearangement /friction
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Mathematical model of compation
Heckel equation one of many equations
assumes the compaction takes place by reducing porosity as the first order process
rel
solid
B
k
p
rel d
drel
B
solid
B
solidB
V
V
V
VV
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relrel kP
1d
d
Akprel
1
1ln
A
01
1ln
ρ0 = rel. density at low pressure
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Types of compaction behavior
Compacting different size fractions of the same material
rel1
1ln
P
rel1
1ln
P
mostly plastic fragmentation
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compaction equipment
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Roller compaction
Compacting powder between rollers
Powder is fed by gravitation or using screw conveyor
Powder is pulled into the gap by action of friction force between the roller surface and the powder
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Critical parameters of roller compaction
ω … angular speed
α … nip angle
γ … angle of max pressure pmax
δ … elastic expansion angle
e … gap size
e1 … size of product ribbon
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Zones between the rollers
Entry zone
powder is not entrained by the rollers
Slip zone
powder is pulled into the gap, but moving more slowly than roller surface
Nip zone
powder is pulled into the gap at the roller surface velocity
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Regions of different material motion
α given by pressure,
layer height and
material properties
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Parametes affecting roller compaction
Geometric
roller diameter, gap size
Operation
Feed pressure, angular velocity
Powder
internal friction angle, bulk density, compressibility
Interface
wall friction angle
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Stress state in the slip zone
Feed pressure
entry/slip zone boundary
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Geometry-compression relationship
V
V
B
B
,
,
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Geometry-compression relationship
sindcos2d 0 RRRhV coscos2 0 RRRhV
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Stress in nip zone
Empirical relationship
K .. compressibility K
2
1
2
1
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Nip angle
Slip zone
stress gradient = function (D, S, θ, δ, φ )
Nip zóne
stress gradient = function (D, S, K)
(for illustration only)
(for illustration only)
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Nip angle
Nip angle belongs to both zones
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Application of compaction in pharma processes – feed screw designs
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compacted products
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compacted product usage
Intermediate product with better flowability
Content of
hard gelatin capsules
sachets
effervescent drugs
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Factors affecting compacts strength
Raw material
particle size distribution
flowability
additives (eg. hydroxypropylcellulose)
vlhkost
Process parameters
recycle
process speed / time-under-pressure
temperature
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Compacted vs. granulated product
Specific properties
lower porosity
smoother surface
No binder necessary
Dry-processing (no moisture)
No drying necessary
thermal stability issues
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Extruding
Pushing the paste-like material through orifice
melt
powder + liquid
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Extruders
Cylinder rolls
Radial
Piston feed
Axial screw
Double-screw
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
(Granulation) / Extrudation / Spheronization (Glatt
process)
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Spheronization
Smooth surface = further improvment of the flowability
Low dust, better coating
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Spheronizing extrudates
Uniform particles
Good dissolution and dispergation
Attractive design
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Powder coating
Creating layered structure
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Controlled Release for powder coating
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Spheronization
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Spheronization / coating process
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Products
powder granulate extrudate spherules/pelets
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Pharmaceutical extrusion Melt-extrusion process
Alternative to tablet compression
Advantages
no granulation, drying
special properties
appearance
Disadvantages
processing temperature
special excipients
solubility
thermoplasticity
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Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Melt-extrusion excipients
Low melting point
Polyethylenglykol
mp. ~ 35 – 60 °C
drug form thermal stability problems
Acceptable metling point
Polyvinylpyrrolidon
mp. ~ 90 – 180 °C
API thermal stability problems
Engineering in Chemical and Pharmaceutical Processes Compaction, Extrusion, Spheronization
Melt extrusion for improving bioavailability
Dispersion of drug in melted water-soluble polymer
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