compression and compaction-2011lect5

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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25

0

20

40

60

80

100

0 5 10 15 20


Porosity(%)


starch

avicel lactose

emcompress


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COMPACTIBILITY PROFILE

0

2

4

6

8

0 1 2 3 4


Hardness(kP) Avicel

Highspeed

Avicel

Low

speed


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0

20

40

60

80

100

0 1 2 3


Porosity(%)

Avicel

High speed

AvicelLow speed



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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

compression and compaction-2011lect5

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