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8/13/2019 Compression and Compaction-2011Lect5
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Compression and compaction
Dr Ali Nokhodchi, PharmD, PhD
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References
Pharmaceutics: the science of dosage
form design. Edited by M.E. Aulton, 2nd
Edition, Chap. 27, pp: 423-439
Remington, the Science and Practice of
Pharmacy, 21st Edition, Chap. 45, Oral
solid dosage Forms, pp:894-896
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Basic Mechanical Unit of
Compression
Die
lower punch
upper punch
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SINGLE TABLETING MACHINE
Time
Displaceme
nt upper
lower
Contact time
Dwell time
force
Time
Ejection forceforce
Time
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ROTARY TABLETING MACHNIE
Die
Upper punch
Lower punch
Upper compression
roll
lower compression
roll
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Rotary tableting machine profile
Displacem
ent
Time
Upper punch
lower punch
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TABLETING PROCESS
HARDNESS
(bonding)
DISSOLUTION
(porosity)
COMPACTIONincrease in mechanicalstrength (consolidation
of particles)
COMPRESSIONreduction in bulk volume
(displacement of gaseous
phase)
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Stage 1: Particle rearrangement
Size of the particles: Small particles
enter the voids between larger particles
Initial porosity of powder bed: The
greater the porosity, the greater the
particle rearrangement
Shape of the particles: Spherical
particles tend to assume closer packing
arrangements than irregular particles
Partic le rearrangemen t : A decrease in the relative
volum e caused b y interparticulate sl ippage of powder
leading to close packing
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Stage 2: Deformation
Elastic deformation: Particlesreturn to their original shape
(deformation disappears completely)
upon release of the stress
Plastic deformation: Particles do
not recover their original shape after
release of the stress
The force required to initiate a plastic
deformation is known as the yield
Deformat ion at point of con tact : Increasing the appl iedpressure causes deformation of th e part ic les = change of
shape.
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Stage 3: Fragmentation
Fracture occurs when the stresses
within the particles become great
enough to propagate cracks.
The fragments infiltrate theremaining voids to increase
densification.
Fragmentat ion : Ini t ia l part ic les are divid ed into a
smaller discrete part ic les.
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Stage 4: Bonding
Bonding : Plast ic deformat ion at the
part ic le interfaces and al ignment of
part ic le su rfaces so that
interpar ticu late bond ing can occu r.
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Stage 5: Deformation of the solid
body
Deformat ion of the so l id body : If the
app l ied pressu re is inc reased fu rther,
the bonded so l id is conso l idatedtowards zero porosi ty
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Stage 6: DecompressionDecompress ion : The interpart icu late bonds
formed must be suf fic ient ly robust towiths tand release of the appl ied pressu re
Removal of the upper punch relieves the axial
pressure but a radial pressure from the die
remains. This allows axial elastic recovery to take
place.
If elastic. If plastic.
Axial elastic
recovery
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Stage 7: Ejection
Eject ion: The pro cess b y which the tablet is
removed from the die cavi ty .
The force necessary to eject the tablet from the die
(EF) must be greater than the quotient of the
residual die wall force (RDWF) exerted from thetablet and the friction between the tablet and the
die wall (w).RDWF
EF
RDWF = Residual Die Wall Force
EF = RDWF *w
w = Coeff. friction at die wall
RDWFRDWF
w
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Example
True density = 1.25 g/cc
Weight = 500 mgDiameter = 10 mm
Thickness after ejection = 7.5 mm
Calculate % ER? Assume at max. pressure porosity is zero
Porosity = 0 it means Volume of powder = volume of tabletVt = weight/density = 0.5/1.25 = 0.4 cm
3
Vt= 3.14 R2H 0.4 = 3.14 (0.5)2 H
H = (0.4)/(3.14 0.25) H = 0.5 cm or 5 mm
ER = [(7.5-5)/5] 100 ER = 50%
100*0
PH
PHH
ERHp: Tablet thickness after compression.
H0: Tablet thickness upon removalof the Compression pressure (it
could be 24 h after the ejection).
Elastic Recovery
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Effect of compression pressure
on a bed of powder
Examples
Paracetamol
Avicel, Starch
Nacl
Dicalcium Phosphate
Lactose
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COMPRESSION
MECHANISMS REVERSIBLETIME
DEPENDENT
ELASTIC(rubber)
YES NO
PLASTIC
(avicel)
NO YES
BRITTLE
(emcompress)
NO NO
VISCO-ELASTIC
(starch)
PARTLY YES
BRITTLE-PLASTIC
(lactose)
PARTLY YES
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COMPACTIBILITY PROFILE
0
2
4
6
8
0 5 10 15 20
Compaction Force (kN)
Hardness
(kP)
starch
avicellactose
emcompress
COMPRESSIBILITY PROFILE
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0
20
40
60
80
100
0 5 10 15 20
Compaction Force (kN)
Porosity(%)
COMPRESSIBILITY PROFILE
starch
avicel lactose
emcompress
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COMPACTIBILITY PROFILE
0
2
4
6
8
0 1 2 3 4
Compaction Force (kN)
Hardness(kP) Avicel
Highspeed
Avicel
Low
speed
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0
20
40
60
80
100
0 1 2 3
Compaction Force (kN)
Porosity(%)
Avicel
High speed
AvicelLow speed
COMPRESSIBILITY PROFILE
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FACTORS IN TABLETING
Press Force Press Speed
Hardness Porosity
Surface Area
Dissolution
Disintegration
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Assessment of plastic deformation.
Scanning electron microscopy:Size of particles after compression remains the same as before
compression although a change in the particle shape could be observed.
Percentage elastic recovery of the compressed tablets:Plastically deforming material exhibit no or small increase in tablet
thickness after storage.
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Assessment of plastic deformation
(Cont inued)
1. Force volume relationships: Heckel
analysis
ln [1/1-D] = kP + A
k and A are constants obtained from the slope and intercept of the plot
Ln(1-/1-D) versus P respectively, D is the relative density of a powderbed at the pressure P
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Heckel plot
-die filling
-Particle
rearrangement
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ln [1/1-D] = kP + A
k = (1/3)Y k gives a measure of the plasticity of a compressed
material
Greater slopes indicate a greater degree of plasticity of materials
The slope was also related to the yield strength (Y) of the material
The reciprocal of k to be the mean yield pressure (PY)
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33True density =5 g/cm3 Weight = 300 mg Diameter =8 mm
1 0.7 0.352 0.853 0.171 0.1871
2 0.6 0.301 0.995 0.199 0.2219
3 0.5 0.251 1.194 0.239 0.2729
4 0.4 0.201 1.493 0.299 0.3546
5 0.35 0.176 1.706 0.341 0.4174
7.5 0.305 0.153 1.958 0.392 0.4969
10 0.3 0.151 1.990 0.398 0.5076
12.5 0.29 0.146 2.059 0.412 0.5307
15 0.28 0.141 2.133 0.427 0.5560
20 0.27 0.136 2.212 0.442 0.5840
30 0.26 0.131 2.297 0.459 0.6150
40 0.25 0.126 2.389 0.478 0.649550 0.24 0.121 2.488 0.498 0.6884
60 0.23 0.116 2.596 0.519 0.7324
80 0.2 0.100 2.986 0.597 0.9092
100 0.15 0.075 3.981 0.796 1.5905
Pressure Thickness App. Vol App. Density Relative ln(1/1-D)
(Mpa) (cm) Cm3 (g/Cm3)
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Slope = 0.0042 MPa-1
Yield pressure = 238 MPa
Q ? True density =4 g/cm3
Weight = 300 mg
Diameter = 8 mm
Ln(1/1-Dr)
y = 0.0042x + 0.4842
R
2
=0.982
0.0000
0.2000
0.4000
0.6000
0.8000
1.0000
1.2000
1.4000
1.6000
1.8000
0 20 40 60 80 100 120Compression pressure (MPa)
Application of Heckel plot
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Application of Heckel plot
100*
2
)12
(
yP
yP
yP
SRS
Strain rate sensitivity
(increase in compression speed increases the mean yield pressure).
High speedLow speed
Exp. Yield pressures for PEG
at low and high speeds are 25
and 50 Mpa respectively,
Calculate SRS and determine
the deformation mechanism?
SRS= [(50-25)/50] x100
SRS = (25/50)x100
SRS = 50%
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Highly fragmenting
Highly plastic
Strain rate sensitivity of some excipients and
drugs
materials SRS(%)
Maize starch
Mannitol
NaCl
Lactose b-anhydrous
Spray dried lactose
A-lactose monohydrate
Paracetamol
Paracetamol DC
DCP
97.12
86.5
66.3
25.5
23.8
19.4
11.9
11.8
0
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Assessment of plastic deformation
(Cont inued)
Reduction in tablet tensile strength or tablethardness with increasing compression
speed.
Compression speed (mm/s)
H
ardness(N)
AVICEL
DCP
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High Lubricant sensitivity (the same
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High Lubricant sensitivity (the same
compression force and speed)
Lubricant concentration (%w/w)
Hardness
(N)
PEG
DCP
compressioncompression
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We require to make ibuprofen tablets, hardness about 100 N.
The results showed that at these conditions the hardness of
tablets is 70 N.
Plastic deforming
drug
Use fragmenting
Excipinets, DCP
Increasecompression
force
Decreasecompression
speed
Conditions:
500 mm/s
10 kN
Ibuprofen 400 mg
Starch 20 mg
Avicel 129 mg
Lubricant 1 mg
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We require to make carbamazepin tablets, hardness about
100 N. The results showed that at these conditions the
hardness of tablets is 70 N.
Highly fragmenting
drug
Use plasticdeforming
Excipinets, Avicel
Increasecompression
force
Decreasecompression
speed
carbamazepin 400 mgStarch 20 mg
DCP 129 mg
Lubricant 1 mg
Conditions:
500 mm/s
10 kN
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Ibuprofen 400 mg
Starch 20 mg
DCP 129 mgLubricant 10 mg
The hardness of ibuprofen tablets for above formulation is less than our target.
Give your approaches to increase the hardness?
1. Reduction in compression speed
2. Increase DCP concentration
3. Increase compression force4. Decrease lubricant concentration
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Assessment of elastic deformation
(Continued)
Energy analysis: Force displacement
profile: High amount of gross energy isspent in bonds disruption: Elastic energy.
High percentage friability
Low tensile strength or tablet hardness
value
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Assessment of Fragmentation
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Assessment of Fragmentation(Continued)
Force volume relationships: Heckelanalysis: High mean yield pressure value.
Not Strain rate sensitive (increase in
compression speed has no effect on themean yield pressure value).
Stress relaxation: Little or no decrease in the
maximum applied compression force withtime.
No reduction in tablet tensile strength with