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Compression and compaction


Dr Ali Nokhodchi, PharmD, PhD
2
References
Pharmaceutics: the science of dosage
form design. Edited by M.E. Aulton, 2
nd
Edition, Chap. 27, pp: 423-439
Remington, the Science and Practice of
Pharmacy, 21
st
Edition, Chap. 45, Oral
solid dosage Forms, pp:894-896
3
Basic Mechanical Unit of
Compression
Die
lower punch
upper punch
4
SINGLE TABLETING MACHINE
Time
D
i
s
p
l
a
c
e
m
e
n
t
upper
lower
Contact time
Dwell time
f
o
r
c
e
Time
Ejection force
f
o
r
c
e
Time
5
ROTARY TABLETING MACHNIE
Die
Upper punch
Lower punch
Upper compression
roll
lower compression
roll
6
55 stations, 495000 tabs/hour
7
8
Rotary tableting machine profile
D
i
s
p
l
a
c
e
m
e
n
t
Time
Upper punch
lower punch
9
10
TABLETING PROCESS
HARDNESS
(bonding)
DISSOLUTION
(porosity)
COMPACTION
increase in mechanical
strength (consolidation
of particles)
COMPRESSION
reduction in bulk volume
(displacement of gaseous
phase)
11
12
13
MAKING A TABLET
UPPER
PUNCH
LOWER
PUNCH
UPPER
PUNCH
LOWER
PUNCH
LOWER
PUNCH
UPPER
PUNCH
LOWER
PUNCH
UPPER
PUNCH
LOWER
PUNCH
Apparent density Tapped density Deformation
Fracture,
Plastic Flow
Fusion
14
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
Particle rearrangement : A decrease in the relative
volume caused by interparticulate slippage of powder
leading to close packing
15
Stage 2: Deformation
Elastic deformation: Particles
return 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
Deformation at point of contact: Increasing the applied
pressure causes deformation of the particles = change of
shape.
16
Stage 3: Fragmentation
Fracture occurs when the stresses
within the particles become great
enough to propagate cracks.
The fragments infiltrate the
remaining voids to increase
densification.
Fragmentation: Initial particles are divided into a
smaller discrete particles.
17
Stage 4: Bonding
Bonding: Plastic deformation at the
particle interfaces and alignment of
particle surfaces so that
interparticulate bonding can occur.
18
Stage 5: Deformation of the solid
body
Deformation of the solid body: If the
applied pressure is increased further,
the bonded solid is consolidated
towards zero porosity
19
Stage 6: Decompression
Decompression: The interparticulate bonds
formed must be sufficiently robust to
withstand release of the applied pressure
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
20
Stage 7: Ejection
Ejection: The process by which the tablet is
removed from the die cavity.
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 the
tablet 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
RDWF RDWF

w
21
Example
True density = 1.25 g/cc
Weight = 500 mg
Diameter = 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 tablet
V
t
= weight/density = 0.5/1.25 = 0.4 cm
3
V
t
= 3.14 R
2
H 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
(
(
(

|
.
|

\
|

=
P
H
P
H H
ER
H
p
: Tablet thickness after compression.
H
0
: Tablet thickness upon removal
of the Compression pressure (it
could be 24 h after the ejection).
Elastic Recovery
22
Effect of compression pressure
on a bed of powder
Examples
Paracetamol
Avicel, Starch
Nacl
Dicalcium Phosphate
Lactose
23
COMPRESSION
MECHANISMS
REVERSIBLE
TIME
DEPENDENT
ELASTIC
(rubber)
YES NO
PLASTIC
(avicel)
NO YES
BRITTLE
(emcompress)
NO NO
VISCO-ELASTIC
(starch)
PARTLY YES
BRITTLE-PLASTIC
(lactose)
PARTLY YES
24
COMPACTIBILITY PROFILE
0
2
4
6
8
0 5 10 15 20
Compaction Force (kN)
H
a
r
d
n
e
s
s

(
k
P
)
starch
avicel
lactose
emcompress
25
0
20
40
60
80
100
0 5 10 15 20
Compaction Force (kN)
P
o
r
o
s
i
t
y

(
%
)
COMPRESSIBILITY PROFILE
starch
avicel lactose
emcompress
26
COMPACTIBILITY PROFILE
0
2
4
6
8
0 1 2 3 4
Compaction Force (kN)
H
a
r
d
n
e
s
s

(
k
P
)
Avicel
High
speed
Avicel
Low
speed
27
0
20
40
60
80
100
0 1 2 3
Compaction Force (kN)
P
o
r
o
s
i
t
y

(
%
)
Avicel
High speed
Avicel
Low speed
COMPRESSIBILITY PROFILE
28
FACTORS IN TABLETING
Press Force Press Speed
Hardness Porosity
Surface Area
Dissolution
Disintegration
29
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.
30
Assessment of plastic deformation
(Continued)
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 powder
bed at the pressure P
31
Heckel plot
-die filling
-Particle
rearrangement
32
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 (P
Y
)
33
True density =5 g/cm
3
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 0.6495
50 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) Cm
3
(g/Cm
3
)
34
Slope = 0.0042 MPa
-1
Yield pressure = 238 MPa
Q ? True density =4 g/cm
3
Weight = 300 mg
Diameter = 8 mm
L
n
(
1
/
1
-
D
r
)
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 80 100 120
Compression pressure (MPa)
35
Application of Heckel plot
100 *
2
)
1 2
(
(
(


=
y
P
y
P
y
P
SRS
Strain rate sensitivity
(increase in compression speed increases the mean yield pressure).
High speed
Low 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%
36
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
37
Assessment of plastic deformation
(Continued)
Reduction in tablet tensile strength or tablet
hardness with increasing compression
speed.
Compression speed (mm/s)
H
a
r
d
n
e
s
s

(
N
)
AVICEL
DCP
38
Q? True density = 2.5 g/cc; Weight = 500 mg; Diameter = 10 mm
Thickness after ejection = 4 mm; Calculate % ER? Assume at max.
pressure porosity is zero.
Porosity = 0 it means Volume of powder = volume of tablet
V
t
= weight/density = 0.5/2.5 = 0.2 cm
3
V
t
= 3.14 R
2
H 0.2 = 3.14 * (0.5)
2
* H
H = (0.2)/(3.14*0.25) H = 2.5 mm
ER = [(4-2.5)/2.5]*100 ER = 60%
100 *
0
(
(
(
(
(
(

|
|
.
|

\
|

=
P
H
P
H H
ER
H
p
: Tablet thickness after compression.
H
0
: Tablet thickness upon removal
of the Compression pressure.
Plastic materials?
Elastic materials?
Fragmenting materials?
Assessment of plastic deformation
39
High Lubricant sensitivity (the same
compression force and speed)
Lubricant concentration (%w/w)
H
a
r
d
n
e
s
s

(
N
)
PEG
DCP
compression
compression
40
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
Increase
compression
force
Decrease
compression
speed
Conditions:
500 mm/s
10 kN
Ibuprofen 400 mg
Starch 20 mg
Avicel 129 mg
Lubricant 1 mg
41
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 plastic
deforming
Excipinets, Avicel
Increase
compression
force
Decrease
compression
speed
carbamazepin 400 mg
Starch 20 mg
DCP 129 mg
Lubricant 1 mg
Conditions:
500 mm/s
10 kN
42
Ibuprofen 400 mg
Starch 20 mg
DCP 129 mg
Lubricant 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 force
4. Decrease lubricant concentration
43
Assessment of elastic
deformation
Scanning electron microscopy and visual
examination: Capping and lamination.
Percentage elastic recovery of the
compressed tablets: Increase in tablet
thickness upon removal of the compression
force or after storage.
44
Assessment of elastic deformation
(Continued)
Energy analysis: Force displacement
profile: High amount of gross energy is
spent in bonds disruption: Elastic energy.
High percentage friability
Low tensile strength or tablet hardness
value
45
Assessment of Fragmentation
Scanning electron microscopy: Impossible to
find any original particle after compression.
Increase in specific area due to a decrease in
geometric mean diameter of the particles after
compression.
Percentage elastic recovery of the
compressed tablets: No change in tablet
thickness upon removal of the compression
force or after storage.
46
Assessment of Fragmentation
(Continued)
Force volume relationships: Heckel
analysis: High mean yield pressure value.
Not Strain rate sensitive (increase in
compression speed has no effect on the
mean yield pressure value).
Stress relaxation: Little or no decrease in the
maximum applied compression force with
time.
No reduction in tablet tensile strength with
increasing compression speed.