Compression and compaction 4rth prof

Compression,
consolidation
and compaction

CONTENTS
• Introduction
• Fundamentals of powder compression
• Powder flow properties
• Mass volume relationship
• References
Contents

COMPRESSION
the reduction in the bulk volume of a material as a result of
the removal of the gaseous phase (air) by applied pressure
CONSOLIDATION
Involves an increase in the mechanical strength of a material
resulting from particle-particle interactions.
COMPACTION
The compression and consolidation of a 2 phase (solid +
gas) system due to an applied force.

DIFFERENCEBETWEENCOMPRESSION
CONSOLIDATION
compaction consolidation
1. It is defines as the formation of solid
specimen of defined geometry by
powder compression.
1 It is increase in mechanical strength of
material from particle – particle
interaction .
2. The compression takes place in a die
by the action of two punches , the lower
and upper by which compression force is
applied .

FUNDAMENTALS OF POWDER COMPRESSION
 In order to study physics of tabletting process, one should have
knowledge about inherent proprties of powders/granules.
 Attractive forces exist between particles vander Waal’s, H-bonding,
Electrostatic consider a number of granules in a die to which a force is
applied

Inherent properties of powder solids
• solid-air interface,
• Powder flow properties (angle of repose, carr`s index,
hausner`s ratio)
• mass volume relationship,
• volume
• density,
• compressibilty

Solid-air interface
Cohesion is the attraction between like particle; Experienced by
particles in bulk.
Adhesion is the attraction between unlike particle; Experienced by
particles at surface.

Powder flow properties:
• Powders may be free-flowing or cohesive (Sticky).
• Many common manufacturing problems are attributes to
powder flow.
1. Powder transfer through large equipment such as hopper.
2. Uneven powder flow  excess entrapped air within
powders  capping or lamination.
3. Uneven powder flow  increase particle’s friction with
die wall causing lubrication problems and increase dust
contamination risks during powder transfer.

4. Powder storage, which for example result in
caking tendencies within a vial or bag after
shipping or storage time.
5. Separation of small quantity of the powder
from the bulk-specifically just before the
creation of individual doses such as during
tableting, encapsulation and vial filling which
affect the weight uniformity of the dose (under
or over dosage).

• Tests to evaluate the flowability of a powder.
1. Carr’s compressibility index. (will be
discussed in comprssibility)
2. Hausner ratio.
3. The angle of repose ().

Hausner ratio
Tapped density
Hausner ratio =
Poured or bulk density
Hausner ratio was related to interparticle friction:
• Value less than 1.25 indicates good flow (=20%
Carr).

Hausner ratio
• The powder with low interparticle friction, such as
coarse spheres.
• V
alue greater than 1.5 indicates poor flow (= 33%
Carr’s Compressibility Index)).
• More cohesive, less free-flowing powders such as
flakes.
• Between 1.25 and 1.5 added glidant
improves flow.
•  1.5 added glidant doesn’t improve flow.
normally

Angle of repose (Dynamic angle)
The maximum angle possible between the surface of pile of non-
cohesive (free-flowing) material and the horizontal plane.
Angle of repose is an indication of
the flow ability of
the material.

Angle of Repose (θ)
θ = tan-1(h/r)
where
h = height of pile
r = radius of the base of the pile
h
r
Angle of
repose
Flow property of
powder
<25 Excellent
25-30 Good
30-40 Passable
>40 poor

METHODS TO MEASURE
ANGLE OF REPOSE.
a.Fixed funnel and free standing cone method.
b.Tilting box method.
c.Revolving cylinder method

Factors affecting the flow
properties of powder
Improvement
of
Powder Flowabilty
Particle’s
size &
Distributio
n
Particl
e
Shape
&
texture
Surfac
e
forces
Flow
Activator
s

1. Alteration of Particle’s size & Distribution
2. Alteration of Particle shape & texture
3. Alteration of Surface Forces
4. Formulation additives (Flow activators)
Factors affecting the flow
properties of powder

Alteration of Particle’s size & Distribution
• There is certain particle size at which powder’s flow
ability is optimum.
• Coarse particles are more preferred than fine ones as
they are less cohesive.
• The size distribution can also be altered to improve
flowability by removing a proportion of the fine
particle fraction or by increasing the proportion of
coarser particle’s such as occurs in granulation.

Alteration of Particle shape & texture
Particle’s Shape
• Generally, more spherical particles have better flow
properties than more irregular particles.
• Spherical particles are obtained by spray drying, or
by temperature cycling crystallization.

Alteration of Particle shape & texture
Particle’s texture
• Particles with very rough surfaces will be more
cohesive and have a greater tendency to
interlock than smooth surfaced particles.

Alteration of Surface Forces
• Reduction of electrostatic charges can improve
flowability.
powder
• Electrostatic charges can be reduced by altering process
conditions to reduce frictional contacts.
• Moisture content of particle greatly affects powder’s flowability.
• Adsorbed surface moisture films tend to increase bulk density
and reduce porosity.
• Drying the particles will reduce the cohesiveness and improve
the flow.
• Hygroscopic powder’s stored and processed under low humidity
conditions.

Formulation additives (Flow activators)
• Flow activators are commonly referred as a
glidants.
• Flow activators improve the flowability of
powders by reducing adhesion and cohesion.
e. g. Talc, maize starch and magnesium stearate.

VOLUME
1. Open intraparticulate voids:those with in a single
particle but open to the external environment.
2. losed interparticulate voids-those within a single
particle but closed to the external environment.
3. Interparticulate voids-the air spaces between
individual particles.
• True volume (VT)
• Granule volume (VG)
• Bulk volume (VB)
• Relative volume (VR)
VR = VB / VT
VR tends to become unity as all air is eliminated from the mass during the
compression process.
Mass-Volume relationships

DENSITY:
The ratio of mass to volume is known as the density of the material
Types of Density:
• True density (ρT = M / VT)
• Granule density (ρG = M / VG )
• Bulk density (ρB = M /VB)
• Relative density (ρR = M / VR)
M is the mass of powder

VTap = Tapped volume of the same mass of powder ≈ VT
Measuring Compressibility:
Carr’s (Compressibility) Index
= [(VB – VTap) / VB] x 100 ≈ E
where
VB = Freely settled volume of a given mass of powder
Carr’s (Compressibility) Index
= [(ρTap – ρB) / ρTap] x 100 ≈ E
where
ρB = Freely settled bulk density of the powder
ρTap = Tapped bulk density of the powder ≈ ρT
Compressibility:
The ability of the powder bed to be compressed (under
pressure) and consequently be reduced in volume.

Carr’s compressibility index
• A volume of powder is filled into a graduated
glass cylinder and repeatedly tapped for a
known duration. The volume of powder after
tapping is measure.
Tapped density- Poured or bulk density
Carr’s index (%)=
Bulk density= weight/bulk volume
Tapped density=weight/true
volume
X
100
Tapped density

Carr’s compressibility index
Flow description % Compressibility
Excellent flow 5 – 15
Good 16 – 18
Fair 19 – 21
Poor 22 – 35
Very Poor 36 -40
Extremely poor  40
Relationship between powder flowability and % compressibility

Consolidation
An increase in the mechanical strength of the
material resulting from particle or particle
interaction. ( Increasing in mechanical strength
of the mass)

Consolidation Process
 Cold welding : when the surface of two
particles approach each other closely enough ,
their free surface energies result in strong
attractive force , a process known as cold
welding.
E.g. At separation of less than 50nm
 Fusion bonding : Multiple point contacts
of particles upon application of load produces
heat which causes fusion or melting. Upon
removal of load it gets solidified & increase
the mechanical strength of mass.

Consolidation Mechanism
Mechanical theory :
 It occurs btw irregular shaped particles.
 Also increases the number of contact points btw the particles
 As the particle undergo deformation , the particle boundaries
that the edges of the particles intermesh , forming a
mechanical bond.
Intermolecular force theory : Under pressure the
molecules at the points of true contact between new , clean
surface of the granules are close enough so that van der waals
force interact to consolidate the particles.
E.g , microcrystalline cellulose is believed to undergo
significant hydrogen bonding during tablet compression

Liquid – Surface film theory :
Thin liquid films form which bond the particles
together at the particles surface . The energy of
compression produces melting of solutions at the
particles interface followed by subsequent
solidification or crystallization thus in the
formation of bonded surface.

Factors affecting consolidation
The chemical nature of the material.
The extent of the available surface.
The pressure of the surface contaminants.
The inter surface distance.

Role of moisture
 Moisture is necessary for formation of tablets.
it can fill the small voids present between the
particles.
Moisture is also important in wet / moist
granulation.
 A small proportion of moisture content is
required in the formulation of tablet.
This moisture content is important for the
mechanical strength of tablet.

If moisture content is less there will be increase
in the die wall friction.
If moisture content is increased there will be
decrease in compact strength .
Moisture content is determined by loss on
drying given by formula
Percentage moisture content=
(loss in wt/ initial wt) x 100

Eg : As a results of increasing compressional
force , result in this water being squeezed out to
the surface of the tablet . This expelled moisture
may act as a lubricant at the die wall, but it
could be cause material to stick to the punch
faces .

Different types of states during
moist granulation
1. Pendular state (powder + binding agent)
2. Funicular state (powder + more binding agent)
3. Capillary state(powder + even more binding
agent)
4. Droplet state(powder + even more & more
binding agent)

 Pendular state :
This state is occurs at low moisture level.
In this state particles are held together by
lens shaped rings of liquid .
These cause adhesion because of the
surface tension force of the liquid – air
interface & the hydrostatic suction
pressure in the liquid bridge.

Funicular state :
This state represents an intermediate stage
btw the pendular & capillary state.
When the air start to displace from btw
the particles , the particles arrange in
funicular state.
After the funicular state ,the particles
arrange themselves in capillary state &
there is no air btw them.

Capillary state :
When all the air has been displaced from
btw the particles the capillary state is
reached .
Moist granules tensile strength increases
about three times btw the pendular & the
capillary state .
This state is most desirable state in the
process of granulation.

 Droplet state
This is another state in the process but this
step is undesirable .
This will be important in the process of
granulation by spray drying of a
suspension.

Compression & Consolidation under
high loads (tablet punch
forces)
Effect of Friction
Force Distribution
Development of radial force
Die-wall lubrication
Ejection force

1. Effect of Friction :
 Frictional forces are inter particulate friction and
die wall friction
 Inter particulate friction occurs due to particle-
particle contact and it is more significant at low
applied load .These forces are reduced using
glidants.
Eg : colloidal silica , talc , corn starch,
 Die wall friction forces occur from material
pressed against die wall and moved, it is dominant
at high applied load. These forces are reduced using
lubricants like magnesium stearate , talc , stearic
acid , waxes etc,

2 . Force distribution :
Most investigations are carried out on single
station presses or even on isolated punches &
die sets in conjugation with hydraulic press,
These must be an axial balance of forces.
 A force is applied on cylinder on top of
cylinder of powder mass

FA=FL +FD
Where…
FA…Applied force to the upper punch FL…Force
transmitted to lower punch
FD…Reaction at die –wall due to friction at
surface

3. Development of radial force :
 As the compressional force is increased & the
repacking of tableting mass is completed ,the material
may be regard as a single solid body.
 Then as with all the solids , compressive force applied
in one direction (eg: vertical) results in a decrease in
ΔH i.e. height
 In case of unconfined solid body , this would be
accompanied by an expansion in the horizontal
direction ofΔD.
 The ratio of these two directional changes is known as
poisson ratio (λ) of the material.
λ=ΔD/ΔH
 λ is characteristic constant for each solid

 Consequently a radial die-wall force
 F R develops.
 Materials with larger values of λ gives rise to larger value of
F R
 The relation ship btw F D & F R is given by the expression :
FD=µw. FR
 µW =coefficient of radial die wall friction.

4. Die-wall lubrication
Most pharmaceutical tablets formulations requires
the addition of a lubricants to reduces friction at the
die wall,
-Die-wall lubricants function by inter posing a film
of low shear strength at the interface btw tableting
mass & die-wall there is some chemical bonding
btw boundary lubricants & the surface of die-wall as
well as at edge of the tablets.
-The best lubricants are those of low shear
strength but have strong cohesive tendency
in direction at right angle to the plane of shear

The shear strength of some
lubricants
Material Shear
strength
Stearic acid 1.32
Calcium stearate 1.47
Hard paraffin 1.86
Magnesium stearate 1.96
Potassium stearate 3.07

5. Ejection force:
Force necessary to eject a finished tablets.
Ejection force for a finished tablets consists of 3
stages
stage-1: Peak force required to initiate ejection
by breaking tablets / die wall adhesion.
stage-2: Small force , that required to push the
tablets up the die wall .
stage-3: Declining force of ejection as the
tablets emerges from the die.

Radial die wall forces and die wall friction also
affects ejection of compressed tablets from die.
The force necessary to eject finished tablet is
known as ejection force
This force can eject tablet by breaking tablet/ die
wall adhesion
Variation occurs in ejection force when lubrication
is inadequate

Measurements of forces
1) Strain Gauge
 A coil of high resistant with length width ratio 2:1
& resistant 100 ohm is suitable.
 During compression the applied force causes a
small elastic deformation of two punches.
 Strain gauge are connected to punch as close to the
compression site . It is deformed as the punch
deformed.
 With the deformation , the length of resistant wire
decreases & its diameter is increases.
 The resulting decrease in resistance I measured by
wheat stone bridge as a recording devise.
 Care must be taken to use low voltage so that
heating effect do not interfere with the strain
measurement.

Diagrametic
represent
ation of
strain
gauge

2) Piezo electric load cells :
 Certain crystals like charge quartz may be used.
When subjected to external force these develop
an electrical charge proportional to the force.
 This transducer is connected to amplifier which
convert the charge in to dc voltage.
 The small piezo – electrical transducer are
connected to upper & lower punch holder of
single station press.
 The disadvantage is the dissipation of charge
with time , hence nit suitable for static
measurement.

Force volume relationship
In many tablets processes , when appreciable force
has been applied, the relationship btw applied
pressure (p) & volume parameters such as porosity E
dose become linear over the range of commonly used
pressure.
- It can be expressed by shapiro equation
Log E =Log E0-K.P.
Where….E0=porosity when pressure is zero
K=constant
P= pressure
- Walker expressed similarly
1/1-E=K1-K2.Log P

Forcevolume relationship.
FIG. Decreasing porosity with increasing
compressional force
for single ended pressing
i) initial repacking of particles
ii) Elastic deformation until elastic limit
is reached.
iii) Plastic deformation or brittle
fracture dominates
iv) Compression of solid crystal lattice
formation
2
27
7
End of compressional process is when
bulk volume = tapped volume.
porosity (E)= 0
Decrease in porosity is due to twoprocess:
1.Filling of large spaces by Interparticulate
Slippage.
2.Filling of small voids by deformation or
fragmentation at high loads.
A more complex sequence of events
during compression process involvesfour
stage as shown in fig.,

• The heckel analysis is a most popular method of deforming
reduction under compression pressure .
• In 1961 Heckel postulated a linear relationship between the
relative porosity (inverse density) of a powder and the applied
pressure.
• The slope of the linear regression is the Heckel constant, a material
dependent parameter inversely proportional to the mean yield
pressure (the minimum pressure required to cause deformation of
the material undergoing compression).
• Large values of the Heckel constant indicate susceptibility to
plastic deformation at low pressures, when the tablet strength
depends on the particle size of the original powder.
• The intercept of the line indicates the degree of densification by
particle rearrangement.
Compression Study - Heckel equation

2
28
8
 It is analogous to first order reaction ,where the pores in the mass are the
reactant , that is:
log 1/E = KyP+ KrE=porosity
P = Applied pressure
Ky= material dependent constant
Ky inversely proportional to it’s yield strength (S)
(Ky= 1/3S)
Kr= initial repacking stage & hence E0
For cylindrical tablet,
P = 4F/л. D2
here, P = applied pressure
D = tablet diameter
F= applied compressional force

E= 100×[1 – 4w/ρt × л ×D2×H]
2
29
9
here, w = weight of tabletting mass.
ρt = true density.
H = thickness of tablet.
Heckel plot (summary):
• Heckel plot is density v/s applied pressure
• Follows first order kinetics.
• As porosity increases compression force also increases
• Thus the Heckel’s plot allows for the interpretation of the mechanism of bonding.
• Materials that are comparatively soft & that readily undergo plastic deformation
retain different degree of porosity , depending upon the initial packing in the die.
• This in turn is influenced by the size distribution, shape etc of the original particles.
Ex: sodium chloride (shown by type a in graph)
• Harder material with higher yield pressure values usually undergo compression by
fragmentation first , to provide a denser packing. Ex: Lactose, sucrose ( shown in
type b in graph).

Type-a (NaCl) plots exhibits higher slop (Ky) then
type-b. because type-a materials have lower yield
stress.
Type-b (Lactose) plots exhibits lower slop
because brittle , hard materials are more
difficult to compress.

APPLICATION OF HECKEL PLOT:
•Used to check lubricant efficacy.
•For interpretation of consolidation
mechanisms.

Compression study- Kawakita
Equation
Pa /C = 1/ab + Pa/a
Where C= degree of volume reduction
a,b= constants characteristic to powder
being compressed
P= pressure
 it is a plot of p/c v/s p

Kawakita Equation modification.
C=Vi – Vp/ Vt = abPa / 1+ bPa
3
3
0
0
C= degree of volume reduction,
Vi= initial apparent volume,
Vp=powder volume under applied pressurePa,
Vt= true volume,
a &b =constants.
LIMITATION: Compaction process can be
described upto certain pressure, above which the
equation is no longer linear.

This equation describes the relationship between the
degree of volume reduction of the powder column
and the applied pressure
The basis for the kawakita equation for powder
compression is that the particles are subjected to a
compressive load in a confined space are viewed as
a system in equilibrium at all stages of
compression, so that the product of the pressure
term and volume term is a constant.

CooperandEaton Equation.
3
31
1
Vi– Vp/ Vi– Vt= C2exp (-K2/Pa ) + C3exp (-K3/Pa)
C2,C3,K2,K3= constants.
LIMITATION : Applies only to single
component analysis.

CONTENTS
INTRODUCTION
METHODS OF GRANULATION
ADVANCED GRANULATION TECHNIQUES
CONCLUSION
REFERENCES

Introduction
Granulation: size elargement process in which
primary powder particles are made to adhere to form
larger, multi particle entities called granules.
It is the process of collecting particles together by
creating bonds between them.`bonds are formed by
slugging or by using binding agents.

Need of granulation:
To avoid powder segregation.
To enhance the flow of powder.
To produce uniform mixtures.
To produce dust free formulations.
To eliminate poor content uniformity.
To improve compaction characteristics of mix.

To avoid powdersegregation.
-Segregation may result in weight variation.

To enhance the flow of powders.
(Higher flowability gives better filling of the dies or
containers)
To produce uniform mixtures.
(Mixtures of various particles tend to segregate in
transport or handling because of differences in
particle size, shape and density)

Dust free formulations.
(Decrease dust generation and reduce
employee exposure to drug product)
To eliminate poor content uniformity.

Methods of granulation
DIRECT COMPRESSION
COMPRESSION GRANULATION
WET GRANULATION

When To Choose DRY method?
Drug dose is too high.
Do not compress well after wet granulation.
Heat sensitive drugs.
Moisture sensitive drugs.
e.g. Aspirin , Vitamins

Steps inDry Granulation
Compaction of powder
Milling
Screening

This method is carried
out By two ways
SLUGGING
ROLLER
COMPACTION
Large tablet produced
in heavy duty tablet
press.
Powder is squeezed
between two rollers to
produce sheet of material
e.g. Chilsonator

Equipments
Has two parts,
 Machine for compressing dry powder to form
compacts.
 Mill for breaking these intermediates to
granule.
e.g. CHILSONATER
HAMMER MILL

Advantages
Less equipments
& space
Eliminate
need of binder
solution
Disadvantages
No uniform color
distribution
Process create
more dust

COMPRESSION granulation
It mainly involves three steps -
 Milling of drug and excipients
 Mixing of drug
and excipients
Tablet compression

CAPPING
EQUIPMENTS
ARE
EXPENSIVE
LAMINATION
1/27/2013

wet granulation
In this, powdered medicament and
other excipients are moistened with
granulating agent.

Steps in wet granulation
1
• Mixing of the drug(s) and excipients
2
• Mixing of binder solution with powder mix. to form
wet mass
3
• Coarse screening of wet mass using a suitable sieve .
(6-12 # screens)
4 • Drying of moist granules.
5
• Screening of dry granules through a suitable sieve
(14-20 # screen).
Contd…

Granulating
liquid
-Volatile
-Non-
toxic
e.g.
Water, Ethanol ,
Isopropanol
Binding
agent-
Natural Polymers:
Starch,
Pregelatinized
Starch
synthetic binders:
PVP, MC, HPMC,
Maltrodextrins

Limitation
of wet
granulation
TIME
EQUIPMENTS
LOSS OF
MATERIAL
SPACE
ENERGY
LABOR

Methods
Single pot granulation
High shear mixture granulation
Fluid bed granulation
Extrusion- Spheronization

Single pot granulation
The granulation is done in a normal
high shear processor and dried in same
equipment.
e.g. Single Pot Processor /
One-Pot Processor

 High shear mixture granulation
Dry Powder mixing (Approx 2-5mins)
Liquid binder addition (Approx 1-2mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules

ADVANTAGES DISADVANTAGES
94
Short processing time.
Lesser amount of liquid
binders required compared
with FBG.
Highly cohesive material
can be granulated.
Increase in
temperature may cause
chemical degradation of
thermolabile material.
 Over wetting of
granules can lead to large
size lumps formation.

Fluid bed granulation
Fluidization is the operation by which fine
solids are transformed into a fluid like state
through contact with a gas.
Granulating and drying can be completed in one step
inside the machine.

-Homogeneous granules.
---Gentle product handling.
--Uniform spraying of all
particles in the fluid bed.
Contd…

Advantages
1.It reduces dust
formation during
processing
2.It reduces product
loss
3.It improves worker
safety.
Disadvantages
1. The Fluid Bed cleaning is
labor-intensive and time
consuming.
2. Difficulty of
assuring
reproducibility.

Extrusion-Spheronization
1.Dry mixing of materials to achieve homogeneous
dispersion.
2.Wet granulation of the resulted mixture to form wet
mass.
3. Extrusion of wet mass to form rod shaped particles.
4. Rounding off (inspheronizer)
5. Drying

Extrusion-Spheronization
Different steps involved in the Extrusion- Spheronization process

Advanced Granulation Techniques
Steam Granulation
Melt Granulation
Moisture Activated Dry Granulation (MADG)
Moist Granulation Technique (MGT)
Thermal Adhesion Granulation Process (TAGP)
Foam Granulation
Pneumatic Dry Granulation (PDG)

Freeze granulation Technology
Steam Granulation
Melt Extrusion Technology
Liquisolid Technique
TOPO Technology
Continuous Flow Technology

 This process is a modification of conventional
wet granulation.
Here steam is used as a binder instead of water.
Steam Granulation

Advantages
1.Uniformly distribution the powder particles.
2. Higher dissolution rate of granules because of larger
surface areagenerated.
3. Time efficient.
4. Maintain sterility.

Disadvantages
1. Requires special equipment for steam generation and
transportation.
2. Requires high energy inputs.
3. Thermolabile materials are poor candidates.
4. More safety measure required.

Here granulation is achieved by the addition of meltable
binder.
Binder is in solid state at room temperature but melts in
the temperature range of 50 – 80˚C.
 Melted binder then acts like a binding liquid.
There is no need of drying phase since dried granules are
obtained by cooling it to room temperature.
Melt Granulation

e.g. Polyethylene Glycol(PEG)
2000, 4000, 6000, 8000
(40-60 0C)
water solublebinders-
water insoluble binders-
e.g.. Stearic acid (46-59 0C),
Cetyl or stearyl alcohol(56-60 0C)

-Time and cost effective
-Controlling and
modifying the release of
drugs
-Water sensitive drugs are
good candidates
Advantages
-Heat sensitive materials are
poor candidates
- Lower-melting-point binder
may melt/ soften during
handling and storage
-Higher-melting-point binders
require high melting temp.
and can contribute instability
problems for heat-labile
materials.
Disadvantages

-Drug is blended with diluents
and powder
-Asmall amount of water (1-4%)
Is sprayed
-Agglomerate formation
(size 150–500μm)
MOISTURE ACTIVATED DRYGRANULATION
In MADG, moisture is used to activate granule formation, without the
need to apply heat to dry the granules.
STAGES
AGGLOMERATION
MOISTURE DISTRIBUTION/
ABSORPTION
-Moisture absorbents like
microcrystalline cellulose or
silicon dioxide, are added while
mixing.
-Moisture redistributionwithin
the mixture.
Entire mixturebecomes
relatively dry.

Advantages:
1.Applicable to more than 90% of the granulation need for
pharmaceutical, food and nutritional industry.
2. Time efficient.
3. Suitable for continuous processing
4. Less energy involved during processing.
Disadvantages:
1. Moisture sensitive and high moisture absorbing API are
poor candidates.

Asmall amount granulating fluid is added to activate dry
binder and to facilitate agglomeration.
Moisture absorbing material like Microcrystalline
Cellulose (MCC) is added to absorb any excess moisture.
Drying step is not necessary.
Applicable for developing a controlled release
formulation.
Moist Granulation Technique (MGT):

Thermal Adhesion Granulation Process (TAGP)
-It is applicable for preparing direct tableting formulations.
-Mixture of API and excipients are heated to a temp. 30-130ºC .
in closed system until granulation.
It provides granules with-
- Good flow properties.
- Binding capacity to form tablets of low friability.
- Adequate hardness.

FOAM
GRANULATION
time
efficient
cost
effective
IR, CR
formulation
water
sensitive
drugs
uniform
binder
distribution
no
overwetting

Freeze granulation Technology
Developed and adopted by ,
Swedish Ceramic Institute (SCI).
-By spraying a powder suspension into liquid nitrogen, the drops
(granules) are instantaneously frozen. In a subsequent freeze-
drying the granules are dried by sublimation of the ice without
any segregation effects.
-Finally it produces spherical, free flowing granules.

TOPO Technology
HERMES PHARMA has developed unique technology for
carrying out single pot granulation.
Requires very small quantity of liquid to start the chain
reaction
Pure water or water-ethanol mixtures are used.
Technology produces granules for tablets which contain at
least one solid crystalline, organic acid and one alkaline or
alkaline earth metal carbonate that reacts with the organic
acid in aqueous solution to form carbon dioxide.
As a result, there are no solvent residues in the finished
products, granules have excellent hardness and stability.

The technology does not need any liquid to start the chain
reaction.
Granulation is carried out in an inclined drum into which
powder is fed at one end and granulate is removed at the
other.
The process produces granule with surface protected by
inactive component that do not harm to sensitive API.
CFtechnology can produce up to 12tons of granules
everyday
Continuous Flow Technology

Key Benefits-
Sensitive APIs are protected .
Granules and effervescents become less sensitive to
humidity and high temperature.
Granules form extremely stable products.
No solvent residues in the final products.

Sr. No. Parameters Method
1 Particle Morphology Optical microscopy
2 Particle Size Distribution Sieve analysis, laser light scattering
3 Nature Powder X-Ray Diffraction
4 Surface Area Gas adsorption
5 Granule Porosity Mercury intrusion methods
6 Granule Strength Development of a Formulation
7 Granule Flowability and Density Hopper Method, Density Apparatus
GRANULATION CHARACTERIZATION:

Physics of tablet compression:
In order to study physics of tabletting process, one should
have knowledge about inherent proprties of
powders/granules.
COMPRESSION CYCLE / PROCESS OF COMPRESSION
In pharmaceutical tableting , an appropriate volume of granules in die cavity is
compressed between an upper & lower punch to consolidate the material into a
single solid matrix , which is finally ejected from die cavity as a tablet.

EVENTS IN PROCESSOF COMPRESSION
1. transitional repacking or particle rearrangement
2. Deformation at point of contact
3. Fragmentation
4. Bonding
5. Decompression
6. Ejection

TRANSITIONAL REPACKING OR PARTICLE
REARRANGEMENT
 Particle size distribution determines initial repacking..
 During initial stage of compression , particle subjected to low pressure , during
this particle moves with respect to each other & smaller particle enters in voids
between larger particle..
 As result volume decreases & density increases spherical particle undergoes
lesser rearrangement than irregular particle…

DEFORMATION ATPOINT OF
CONTACT
 When a force is applied on a material deformation occur .
 If the deformation disappear completely (return to original
shape) upon release of stress , it is said to be ‘ elastic
deformation’
 A deformation that not recover completely after removal of
stress known as ‘plastic deformation’.
 The force required initial plastic deformation is known as
‘yield stress’
 When granule particle so closely no further filling voids
occurs ,hence further increase of compression force cause
deformation at point of contact …

FRAGMENTATION
Compression forces increases particle starts
fragmentation because of high load , particle
breaks into smaller fragment leading to formation of
new bonding area.
Fragmentation undergoes densification & infiltration
of small fragments into voids .

BONDING
cold welding :-
When particle approach each other unsatisfied forces present on their
surface leads formation of strong attractive forces called ‘cold
welding’..
Fusion bonding:-
Particle irregular in shape heat transmission leads increase
mechanical strength .
Factor affecting bonding:-
i. Chemical nature of material
ii. Available surface
iii. Presence of surface contaminant

DECOMPRESSION
 The success or failure of intact tablet depends on stress induced by
‘elastic rebounds’ & the association deformation produced during
decompression & ejection .
Capping is due to unaxial relaxation in die cavity ..
Ejection
As the lower punch rises & pushed tablet upward , there is continues
residual die wall pressure & energy may be expanded due to die wall
friction.

Tablet introduction and
manufacturing process

INTRODUCTI
ON
• Tablets are compressed solid unit dosage
form containing medicament or
medicaments usually circular in shape
and may be flat or biconvex.
• Tablet is defined as a compressed solid dosage
form containing medicaments with or without
excipients.
• Pharmaceutical tablets are solid, flat or biconvex
dishes, unit dosage form, prepared by
compressing a drugs or a mixture of drugs, with
or without diluents.
• It is the most popular dosage form and 70% of the
total medicines are dispensed in the form of
Tablet.

• Advantages of
tablets:
 Easy to administered.
 Easy to dispense.
 More stable.
 Accuracy in dose.
 Bitter and nauseous substance can be easily dispensed.
 Light and compact.
 Economical.
 Sustained release product is possible by enteric coating.
• Disadvantages of tablets:
 Problem with compression to crystalline drug.
 Hygroscopic drugs are not suitable for compressed tablets.
 Drugs with low or poor water solubility, slow dissolution, may be
difficult to formulate.
 Cost of production may be increase because of coating and
encapsulation to
remove bitter and unpleasant taste.
 Swallowing is difficult especially for children and ill (unconscious)
patients.

1. Compressed
tablet, e.g.
Paracetamol
tablet
2. Multiple
compressed
tablets,
3. Delayed
release tablet,
e.g. Enteric
coated
Bisacodyl
tablet
4. Sugar
coated
tablet, e.g.
Multivitamin
tablet
(A) Tablets
ingested
orally
1. Buccal tablet,
e.g.
Vitamin-c tablet
2. Sublingual
tablet,
e.g. Vicks
Menthol
tablet
3. Troches
or
lozenges
4. Dental
cone
(B) Tablets
used in oral
cavity
1.
Implantatio
n tablet,
e.g.
Testosterone
tablet
2. Vaginal
tablet,
e.g.
Clotrimaz
ole tablet
(c) Tablets
administered
by
other route
1. Effervescent
tablet, e.g.
Disprin
tablet (Aspirin)
2. Dispensing
tablet, e.g.
Enzyme
tablet (Digiplex)
3.
Hypoder
mic
tablet
4. Tablet
triturates
e.g. Enzyme
tablet
(Digiplex)
(D) Tablets
used to
prepare
solution:
TYPES OF TABLET

TABLETS INGESTED ORALLY
1. Compressed tablet: These are uncoated tablets made by compression of granules. These
provides rapid disintegration and drug release. e.g. Paracetamol tablet.
2. Multiple compressed tablet: These tablets are prepared to separate physically or
chemically incompatible ingredients or to produce repeat action or prolonged action
products. The ingredients of formulation are compressed into a core tablet and the
incompatible substance with other excipients are compressed over the previously
compressed core tablet.
3. Sustained action tablet: These tablets when taken orally release the medicament in a
sufficient quantity as and when required to maintain maximum effective concentration of
drug in the blood.
4. Enteric coated tablet: These tablets are coated with the material which does not
disintegrate in stomach but passes through as it is i.e. enteric polymer e.g.:
Hydroxypropyl methyl cellulose phthalate etc. These tablets dissolve in intestine and are
site specific.
5. Sugar coated tablet: The compressed tablets with sugar coating are called sugar coated
tablets. It is done to mask the bitter and unpleasant taste and odour of the medicament. It
enhances the appearance and protects the drug from atmospheric effects. e.g. Multivitamin
tablet
6. Film coated tablet: These are the compressed tablets having a film coating of film coating
polymer like hydroxy propyl cellulose, ethyl cellulose , HPMC. It also protects the
formulation from atmospheric effects. These are tasteless, have increase in tablet weight
and have less elegance. e.g. Metronidazole tablet
7. Chewable tablet: These tablets are chewed in mouth and are broken into small pieces.

ORAL CAVITY TABLETS
1. Buccal Tablets:
These tablets are to be placed in buccal pouch or between the gum & lip or cheek.
Tablet dissolve & disintegrated slowly & absorb directly.
2. Sublingual Tablet:
These tablets are to be placed under the longue. They dissolve & disintegrated
quickly & absorbed directly without passing into G.I.T. Buccal and sublingual
tablet should be formulated with bland excipients, which do not stimulate
salivation.
3. Lozenge tablet & troches:
These tablets are designed to exert a local effect on mouth or throat. These tablets
are usually used in treatment of sore throat or control coughing. The tablets are
usually used to such drug as anaesthetic, antiseptic and antibacterial agent,
demulcent, astringent and antitussive agent. Lozenges were earlier called pastilles.
4. Dental cones:
These are relatively minor compressed tablet meant for placing them in the empty
socket after tooth extraction. Usually, these tablets contain an antibacterial,
compound which is released slowly. Prevent the growth of bacteria. These tablets
may contain an astringent or coagulant to reduce bleeding. The base for these
types is sodium bicarbonate, sodium chloride or it may be amines acid. These
cones generally get dissolved in 20 to 40 min time.

TABLETS ADMINISTERED BY
OTHER ROUTE
1. Implantation tablet:
These tablets are placed below the skin or inserted subcutaneously by
means of a minor surgical operation and are slowly absorbed. These must
be sterile and are made by heavy compression and fusion. e.g.
Testosterone tablet.
2. Vaginal tablet:
These tablets are meant to dissolve slowly in vaginal cavity. These are
ovoid or pear shaped and are used to release steroids, antibacterial and
antiseptics etc to avoid infections. e.g. Clotrimazole tablet.

TABLETS USED TO PREPARE
SOLUTIONS
1. Effervescent tablet:
These tablets when added in water produce effervescence. So they
dissolved rapidly in water due to the chemical reaction which takes place
between alkali bicarbonate and citric acid or tartaric acid. These tablets
are to be protected from atmospheric moisture during storage (in well
closed container). e.g. Disprin tablet (Aspirin)
2. Dispensing tablet:
These are intended to be added to a given volume of water to produce a
solution of a given concentration. The medicaments given are silver
proteinate and quaternary ammonium compounds. These are highly toxic
if taken orally and great care must be taken in packaging and labelling.
e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet:
These are compressed tablets which are composed of one or more
drugs. These tablets are dissolved in sterile water and administered
parenterally.
4. Tablet triturates:
These are small cylindrical, moulded or compressed tablets which
contains a potent medicament with a diluent. On small scale hand
operated whereas for bulk production automated machines are used.
e.g. Enzyme tablet (Digiplex)

EXCIPIENTS IN TABLET
FORMULATION
1. Diluents: The diluent is needed to increase the bulk
when quantity of medicament is very small in each
tablet. e.g. Lactose, sucrose, sodium chloride,
dextrose and starch etc.
2. Disintegrating agents: To break the tablet in smaller
particles when swallowed. These acts by three ways:
swelling, by producing effervescence and by melting at
body temperature. The disintegrating agent is divided
into two parts. One part is mixed with other excipients
before granules formation and the other is mixed with the
dry granules before compression. e.g. Potato, maize,
wheat starch etc.
3. Granulating agents: These provides moisture to convert
the fine powder into damp mass which after passing
through sieve forms granules. e.g Starch paste, acacia,
tragacanth. gelatin solution, iso propyl alcohol etc.
4. Glidants: To improve the flow properties of
granules. e.g magnesium stearate &Talc

5. Lubricants: To reduce the interparticular friction during
compression and between tablet and die wall during
ejection of tablet. e.g. Talc & magnesium stearate.
6. Binding agents: these provides strength to the
granules to keep the tablet intact and selection of
which depends on the type of tablet.e.g. gum
tragacanth, methyl cellulose etc.
7. Adsorbing agents: these are used to adsorb volatile
oil, liquid extracts and tincture etc. Prevent sticking e.g.
Mg stearate, steraric acid etc.
8. Colors, flavors and sweetening agents: All coloring
agents must be approved and certified by FDA. Two
forms of colors are used in tablet preparation – FD &C
and D & C dyes. These dyes are applied as solution in
the granulating agent or Lake form of these dyes.

Tablets manufacturing
• Tablets are commonly manufactured by wet granulation, dry
granulation or direct compression. These methods may be
considered to consist of a series of steps (unit processes) –
weighing, milling, mixing, granulation, drying, compaction,
(frequently) coating and packaging. Regardless of the method
used the unit processes – weighing, milling and mixing, are
the same; subsequent steps differ.

Primary goals of tablet manufacturing process
• To formulate tablets that are strong and hard to withstand
mechanical shock encountered during manufacturing, packing,
shipping, dispensing and use.
• To formulate tablets that are uniform in weight and in drug content.
• To formulate tablets that are bioavailable according to indication
requirements.
• To formulate tablets that are chemically and physically stable over a
long period of time.
• To formulate tablets that have elegant product identity which is free
from any tablet defects.

Personnel requirements during manufacture of
pharmaceutical tablets
• Production pharmacists/ supervisors
• Manufacturing chemist
• Analytical chemist
• Quality assurance manager
• Machine operators
• Mechanics

Tablet Manufacturing Equipment/ Machines
Common equipment used in pharmaceutical
tablet manufacturing include:
1. Size reduction equipment
e.g., Hammer mill , roller mill , fluidized
energy mill , cutter mill and ball mill
2. Weighing balance/ balances e.g., bulk
weighing balance (weighs in kilogram),
electronic weighing balance (weighs in
grams and milligrams).

3. Mixing equipment e.g.,
pneumatic
tumbling
mixers diffusion/
mixers (e.g., V-
blender, double cone blender,
cubic mixer, drum blender),

4.Granulators e.g. , Rotating
shape granulators , dry granulator ,
high shear granulator etc
5.Drying equipment e.g. spray
dryer , rotary dryer , fluidized bed
dryer etc
6.Tableting machine e.g. single
punch tablet press and multi station
/rotary tablet press

7. Quality control equipment
e.g., disintegration equipment , USP
Dissolution Tester, Tablet Hardness Tester,
Tablet Thickness Tester, Tablet Friability
Testers etc.
8.Coating and polishing machines for
coated tablets e.g., standard coating pan,
perforated pan, fluidized bed/ Air
suspension coating system etc.
9. Packaging machines e.g., blister
packaging machines, strip packing
machine, aluminium foil packaging
machine, etc.

Layout of Tablets
manufacturing
section

Procedure for Manufacturing Tablets
• Dispensing: Each ingredient in the tablet formula is
weighed and accurately dispensed as per dose. This is
one of the critical steps in any type of formulation
process and should be done under technical
supervision.
• Sizing: Formulation ingredients must be in finely
divided form, otherwise, size reduction should be
carried out for better flow property and easy mixing.

• Powder
suitable
blending: Powders
blender to obtain
are mixed using a
a uniform and
homogeneous powder mix. The drug substance and
excipients are mixed in geometric dilution.
• Granulation: Here small powder particles are
gathered together into layers, and permanent
aggregates to render them into free-flowing states.
• Drying and dry screening: Screened wet granules
need to be dried for a particular time period in tray
dryer or fluid bed dryer at controlled temperature not
exceeding 550 degree C . Dried granules are screened
through the appropriate mesh screen

• Tablet compression: This step involves the
compression of granules into a flat or convex, round,
oblong, or unique shaped, scored or unscored tablets;
engraved with an identifying symbol and/ or code
number using tablet press.
• Coating: Tablets and granules are coated if there is
need to mask the unpleasant taste/odour of some drug
substance or to increase the aesthetic appeal of
uncoated tablets as well as to modify the release or
control the release of drug substance from tablets.
This is achieved by enclosing or covering the core
tablet or granules with coating solutions.

Methods used in tablet Formulation
Tablets are commonly manufactured by
• Wet granulation
• Dry granulation or
• Direct compression

WET GRANULATION
• Wet granulation is a widely used method for
the production of compressed tablet. It is
essentially a process of size enlargement
involving several steps and the use of an
adhesive substance known as binder.
• The granulesproducedusing this method of
meeting
al
l
granulation has a greater probability of
the physical requirements for
tablet
formation.

Methods:
1.Weighing, milling and mixing of the APIs
with powdered excipients (excluding the
lubricant)
2. Preparation of binder solution
3.Mixing of binder solution with powders to
form a damp mass
4.Screening the dampened powder into
pellets or granules (wet screening) using 6-
to 12-mesh screen
5. Drying of moist granules

6.Sizing the granulationby dry screening
using 14- to 20-mesh screen
7.Mixing of the dried granuleswith
lubricant and disintegrates
8. Compression of granules into tablets

• Advantages:
1. ¨ Reduced segregation of formulation components
during storage and/or processing
2. ¨ Useful technique for the manufacture of tablets
containing
low and or high concentrations of therapeutic agent
3. ¨ Employs conventional excipients and therefore is
not dependent on the inclusion of special grades of
excipients
• Disadvantages:
1. Often several processing steps are required
2. Solvents are required in the process: this leads to a
number of
concerns:
• Drug degradation may occur in the presence of the
solvent.
• The drug may be soluble in the granulation fluid.
• Heat is required to remove the solvent.

DRY GRANULATION
• The formation of granules by compacting
powder mixtures into large pieces or compacts
which are subsequently broken down or sized
into granules (often referred to as dry
granulation, double compression or pre-
compression) is a possible granulation method
which, however, is not widely used in the
manufacture of tablets.

Dry granulation method
• Weighing and Milling of
formulation ingredients (drug
substance and excipients)
• Mixing of milled powders.
• Compression of mixed powders into slugs.
• Milling and sieving of slugs.
• Mixing with disintegrate and lubricant.
• Compression into tablet.

• Advantages
1. These methods are not generally associated with
alterations in drug morphology during processing.
2. No heat or solvents are required.
• Disadvantages
1. Specialist equipment is required for granulation by
roller compaction.
2. Segregation of components may occur mixing.
3. There may be issues regarding powder flow.
4. The final tablets produced by dry granulation tend to be
softer than those produced by wet granulation
5. Slugging and roller compaction lead to the
generation of considerable dust.

DIRECT COMPRESSION
• direct compression involves direct
compression of powdered materials into tablets
without modifying the physical nature of the
materials itself.
• Direct compression avoids
with
many of the
wet and dry
problems associated
granulations.

Its successful application in tablet formulation
rests on two fundamental issues:
• The availability of suitable excipients
• The availability of suitable machinery.

Flow chat of direct
compression

Dry granulation method .
• Milling of therapeutic agent and excipients
• Mixing of milled powders, disintegrates and
lubricants
• Compression into tablet

• TABLET COATING:
• Reasons for coating:
1. To mask unpleasant taste and odour.
2. To improve the appearance of tablets.
3. To prevent the medicament from atmospheric
effects.
4. To control the site of action of drugs.
5. To produce the sustained release product.
• Methods of tablet coating :
1. Sugar coating:
2. Film coating
3. Enteric coating.

• SUGAR
COATING:
• Steps of sugar coating of
tablet:
1.
2.
3.
4.
5.
6.
Sieving :-
The tablets to be coated are shaken in a suitable sieve to remove the fine powder or broken
pieces of tablets.
Sealing :-
Sealing is done to ensure that a thin layer of water proof material, such as, shellac or
cellulose acid phthalate is deposited on the surface of the tablets. The shellac or cellulose
acid phthalate is dissolved in alcohol or acetone & its several coats are given in coating pan.
A coating pan is made up of copper or stainless steel. The pan is rotated with the help of an
electric motor.
Sub coating :-
In sub coating several coats of sugar & other material such as Gelatin, Acacia etc. are given to
round of tablet and to help in building up to tablet size. Several coats of concentrated syrup
containing acacia or gelatin are given. After each addition of the syrup, dusting powder is
sprinkled. The dusting powder is a mixture of starch, talc & powdered acacia.
Syrup coating :-
This is done to give sugar coats, opacity & colour to tablets. Several coats of the syrup are
applied. Colouring materials & opacity agent are also added to the syrup The process of
coating is repeated until uniform coloured tablets are obtained.
Finishing :-
Three to four coats of sugar are applied in rapid succession without dusting powder and
cold air is circulated to dry each coat. Thus forms a hard smooth coat.
Polishing :-
Beeswax is dissolved in organic solvent and few coats of it are given. The finished tablets
are transferred to a polishing pan is rotated at a suitable speed so the wax coated tablets
are rubbed on the canvas cloth. This gives a proper shining to the tablets. Sugar coating is
an art.

• FILM COATING:
• In this tablets are coated by a single or mixture of film forming
polymers, such as Hydroxypropyl methyl cellulose, Hydroxy ethyl
methyl cellulose, methyl cellulose, carbowax, PEG 400 etc. the
polymer is dissolved in some volatile organic solvent and is sprayed
over the tablets in a rotating pan.
• It is also used to make tablets waterproof before sugar
coating. Film coating may be enteric or non enteric.
• Advantages:
• It is a less time consuming technique.
• Not much labour is required.
• It has no adverse affect on disintegration of tablets.
• Product cost is less.
• It protects the drug from the atmospheric changes such as light,
air and moisture.
• Coating is resistant to cracking and chipping.
• It does not increase the weight of the tablet.
• No waterproofing is required before actual film coating.

• ENTERIC COATING:
Enteric Coated tablet:
• These tablets are coated with the material which does
not disintegrate in stomach but passes through as it is
i.e. enteric polymer e.g.: Hydroxypropyl methyl
cellulose phthalate etc.
• These tablets dissolve in intestine.
• These are site specific.
Enteric coating is given to the tablets when:
1. Medicaments produce severe irritation in stomach.
2. Action required in intestine.
3. Medicament may decompose or destroyed by stomach
pH.
4. Drug absorption is better in intestine.
5. Delayed action is needed.

• MICROENCAPSULATION:
• Microencapsulation:
• Micro-encapsulation is a process in which tiny particles or droplets are
surrounded by a coating to give small capsules of many useful properties.
• In a relatively simple form, a microcapsule is a small sphere with a uniform
wall around it.
• The material inside the microcapsule is referred to as the core, internal
phase, or fill, whereas the wall is sometimes called a shell, coating, or
membrane.
• Microencapsulation techniques:
The methods are based on:
1.Chemical Processess
2.Mechanical Processess
• The following techniques are commonly used:
1. Pan coating
2. Fluidised bed coating
3. Coacervation
4. Electrostatic deposition
5. Polymerisation
6. Multi-orifice centrifugal process

• Most microcapsules have diameters between a few
micrometers and a few millimeters.
• Applications:
1. To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin
etc.
2. To reduce gastric and other gastro intestinal (G.I) tract
irritations, For eg., sustained release.
3. A liquid can be converted to a solid for easy handling and
storage,
4. Hygroscopic properties of core materials may be reduced by
microencapsulation.
5. Protection against external environment.
6. Microencapsulation has been employed to provide protection
to the core materials
7. Separation of incompatible substance has been achieved by
encapsulation.

DEFECTS IN TABLETS
1. Capping:
• In this there is partial or complete removal of top or bottom
portion
of tablet.
Reasons:
1. Excessive fine.
2. Defective punch die.
3. High speed of machine.
4. Granules too dried.
• Defect can be removed:
1. Setting the die and punch properly.
2. Reduce % of fine.
3. Punches should be polished.
4. Maintain the desire moisture in granules.
5. Maintain the speed at optimum & regulate the pressure of
punches.

2. Picking and sticking:
• The material is removed or picked up by upper punch from the
upper surface of the tablet. In the sticking he material stick to the
wall of the die cavity.
• Reasons:
1. Use of worn out die and punch.
2. Use of small quantity of lubricants.
3. Presence of excess moisture in the granules.
4. Scratches on the surface of the face of the punches.
5. Defect in formulation.
• Defect can be removed:
1. Using new set of die and adding proper quantity of
lubricants in granules.
2. Dry granules.

3. Mottling:
• An unequal distribution of colour on the surface of a coloured tablet.
• Reasons:
1. Migration of dye in the granules during drying.
2. Use of different coloration of medicaments and excipients.
3. Defect can be avoided:
4. Drying the granules at low temperature.
5. Using the dye which can mask the colour of all medicaments.
4. Weight variation:
• Weight variation occur during the compression of granules in a tablet
machine and the tablet do not have the uniform weight.
• Reasons for this defect:
1. Granules are not in uniform size.
2. Presence of excess amount of powder in the granules.
3. No proper mixing of lubricants and no uniform flow of granules.
4. During compression change in capacity of die.
5. Variation in the speed of the tablet machine.

5. Hardness variation:
• The tablet do not have a uniform hardness.
• It depends on the weight of the material and space
between the upper and lower punch during the stage of
compression.
• If volume of the material varies and distance varies between
punches, the hardness also varies.
6. Double impression:
• This effect occur when the lower punch has a monogram or
some
other engraving on it.
• During compression, tablet receive an imprint of the punch.
• Due to some defect in he machine lower punch move
slightly upward before ejection of tablet and give
second impression.
• This can be controlled by managing the movement of
punch.

EVALUATION OF TABLET
• Official tests:
1.Size and shape and appearance of
tablet.
2. Content of active ingredient.
3. Uniformity of weight/weight variation
test
4. Uniformity of content
5. Disintegration.
6. Dissolution.
• Unofficial tests:
1. Hardness test.
2. Friability

Official tests
1. Size, shape & appearance:
• General Appearance: The general appearance of a tablet, its
identity and general elegance is essential for consumer
acceptance, for control of lot- to-lot uniformity and tablet-to-tablet
uniformity. The control of general appearance involves the
measurement of size, shape, color, presence or absence of odor,
taste etc.
• Size & Shape: It can be dimensionally described & controlled. The
thickness of a tablet is only variables. Tablet thickness can be
measured by micrometer or by other device. Tablet thickness should
be controlled within a ± 5% variation of standard value.
• Unique identification marking: These marking utilize some form of
embossing, engraving or printing. These markings include company
name or symbol, product code, product name etc.
• Organoleptic properties: Color distribution must be uniform with no
mottling. For visual color comparison compare the color of sample
against standard color.

2. Content of active ingredient
• Procedure:
• Perform the assay of 20 tablets as per monograph
• The result should lie within the range for the content of
active ingredient stated in the monograph.
• If small no. of tablets (min 5) are used then the limits specified
in the monograph may be relaxed to the extent indicated in the
table.
Weight of medicament
in each tablet
Subtract from the
lower
limit for sample of
Add to the upper limit
for sample of
15 10 05 15 10 05
0.12 g or less 0.2 0.7 1.6 0.3 0.8 1.8
>0.12 g &< 0.3 g 0.2 0.5 1.2 0.3 0.6 1.5
0.3 g or more 0.1 0.2 0.8 0.2 0.4 1.0

3. Uniformity of weight:
• Weigh 20 tablets selected at random and determine their
average weight. Not more than 2 of the individual weights
may deviate from the average weight by more than the
percentage deviation given in the table and none should
deviate by more than twice that percentage.
Sr.
No.
Average Wt. of a tablet deviation Percentage (%)
1 80 mg or less 10
2 More than 80 mg and less than 250 mg 7.5
3 250 mg or More 5

4. Uniformity of content:
• Content uniformity test:
• It is used to ensure that every tablet contains the
amount of drug substance intended with little variation.
• Procedure:
• 10 tablets are assayed,
• 9 tablets should have % limit of 85-115%.
• If more than 1 tablet deviates from 85-115%,
• 20 tablets are assayed
• Not more than 1 tablet should have the % limit of 75-
125%

5. Disintegration test:
• Disintegration of a tablet means to break a tablet into smaller particles after
swallowing. The time required to disintegrate the tablet is called disintegration
time.
• The apparatus consists of a rigid basket-rack assembly supporting 6
cylindrical glass tubes held vertically by two superimposed transparent plastic
plates with six holes having the same diameter as the tubes. Woven wire
gauze made from stainless steel is attached to the underside of the lower
plate. The assembly should be raised and lowered between 28 and 32 times
per minute in the liquid at 370 C.
• The tablets are kept immersed in the liquid within the tubes by means of
cylindrical guided discs. The assembly is suspended in the liquid medium in
a 1000 ml beaker. The apparatus is operated generally for 15 minutes and
observed for disintegration of tablets.
• The tablets pass the test if all the tablets disintegrate. In case one or two
tablets fail to disintegrate, repeat the test on 12 additional tablets. The
tablets pass the test if not less than 16 of the total 18 tablets tested have
disintegrated.

• For Uncoated tablets:
1. Start the disintegration test on 6 tablets, if one or two tablets from the 6
tablets fail to disintegrate completely within 30min, repeat the same test on
another 12 tablet.
2. Not less than 16 tablets should disintegrate completely within the time
and if more than two tablets (from the 18) fail to disintegrate, the batch
must be rejected.
• For Coated tablets:
1. To remove or dissolve the coat, immerse the tablet in distilled water for 5 min.
2. Put the tablet in the apparatus in water or 0.1 N HCl for 30min at 37oC
(according to the U.S.P).
3. If not disintegrated, put in intestinal fluid. If one or two tablets fail to
disintegrate,
repeat on 12 tablets.
4. So 16 tablets from the 18 must completely disintegrate within the time.
5. If two or more tablets do not disintegrate within the time the batch is rejected.
• For Enteric coated tablets:
1. Put the tablet in distilled water for five minutes to dissolve the coat.
2. Put in simulated gastric fluid for two hours (emptying time)
3. Put in phosphate buffer (PH 6.8) for one hour.
4. If one or two tablets fail to disintegrate repeat on 12 tablets.
5. So 16 tablets should disintegrate. If more than two tablets fail to
disintegrate, reject the batch.

6. Dissolution test:
• It is the solubilization of the drug or active moiety in to the dissolution
media.
• It is done for measuring the amount of time required for a given percentage
of the drug substance in a tablet to go into solution under specified
condition.
• Apparatus:
1. A cylindrical vessel (made up of glass or other transparent material)
having 1000 ml capacity, fitted with a lid having four holes, one for
shaft of stirrer, second for placing the thermometer and remaining two
for sample removal.
2. An electric motor
3. A cylindrical stainless steel basket made of wire with aperture size of
425 µm
attached to the disc on the driving shaft.
4. Suitable device for withdrawal of sample.

• Method:
• Place 1000 ml of water into the vessel. Place the specified
number of tablets in the dry basket and set the apparatus.
Start the motor and adjust the temperature and rotation
speed to 36.5◦c to 37.5◦c and 100 rpm or as given in
monograph. Withdraw the sample after specified time
intervals. Filter and determine the amount of active
ingredient present in it by the method given in the
monograph.
• Acceptance criteria:
1. S1= 6 tablets are taken Acceptable: If all of the tablets are not
less
than Q ±5%
2. If S1 fails, S2=S1+6 tablets are taken Acceptable: If average
of 12 tablets is ≥Qand no tablet is lessthan Q-15%
3. If S2fails, S3=12+12 tablets are takenAverageof 24 ≥ Q%not more
than 2 tablets should be less than Q-15% and None should be
less than Q-25%

Unofficial tests
1. Hardness test:
• It is defined as the force required to break a tablet in a diametric
compression test. Tablet requires a certain amount of strength or
hardness and resistance to friability to withstand mechanical
shocks of handling in manufacture, packaging and shipping
• Types of hardness testers used are:
• 1. Monsanto hardness tester.
• 2. Strong cob tester.
• 3. Pfizer tester.
• Conventional tablets hardness: 2.5- 5 kg/sq cm
• Dispersible/ chewable tablets hardness: 2.25- 2.5 kg/sq cm
• Extended release tablets hardness: 5- 7.5 kg/sq cm

2. Friability test :
• It is performed to evaluate ability of the tablet to with stand wear
and tear in packing, handling, and transporting.
• The apparatus used to perform this test is known as
"Friabilator".
• The apparatus consists of a plastic chamber, which is divided
into two
parts and it revolves at a speed of 25 rpm.
• Twenty tablets are weighed and placed in a plastic
chamber. The chamber is rotated for 4 minutes or 100
revolutions.
• During each revolution the tablet falls from a distance of 6 inch.
• The tablets are removed from the chamber after 100 revolutions
and weighed. Loss in weight indicates the friability. The tablets
are considered to be of good quality if the loss in weight is less
than 0.8%.

Quality control of tablets
Official tests
• Content of active ingredient/ absolute drug
content test/ assay of active ingredient.
• Weight uniformity test/ weight variation test
• Content uniformity test
• Disintegration time test
• Dissolution test

• UNIFORMITY OF CONTENT
As per IP : 10mg / less than 10% w/w of
active ingredient
As per BP/USP : 25mg /less than 25%w/w
• DISINTEGRATION TEST
As per IP : 28-32 cycle per min
As per BP/USP : 29-32 cycle per min

JSS College of Pharmacy,
Disintegration testing condition and interpretation (IP)
Sr.
No
Type of tablets Medium Temperatu
re
Limit
1 Uncoated Water/buffer 37 °± 2 °C 15 min or as per individual
monograph
2 Film coated Water 37 °±2 °C 30 min or as per individual
monograph
3 Sugar coated Water/0.1
N HCl
37 °±2 °C 60 min or as per individual
monograph
4 Dispersible
Tablets
Water 25 °±1 °C 03 min or as per individual
monograph
5 Effervescent
Tablets
Water 25 °±5 °C 05 min or as per individual
monograph
6 Enteric-coated
Tablets
0.1 M HCl
mixed
phosphate
buffer pH
6.8
37 °±2 °C 02 hour in HCl: no disintegration
60 min in buffer : disintegrate
7 Soluble Tablets Water 20 °±5 °C 03 minutes

JSS College of Pharmacy,
Disintegration testing condition (USP)
Sr.
No
Type of tablets Medium Temperatu
re
Limit
1 Uncoated Water/as specified
in monograph
37 °± 2 °C As per individual monograph
2 Coated Water/as specified
in monograph
37 °±2 °C As per individual monograph
4 Enteric-coated
Tablets
Simulated gastric
fluid TS
Simulated
intestinal fluid TS
37 °±2 °C 01 hour in Simulated gastric fluid
As per individual monograph:
Simulated intestinal fluid TS
5 Buccal Tablets Water/as specified
in monograph
37 °± 2 °C 4 hour
6 Sublingual
tablets
Water/as specified
in monograph
37 °± 2 °C As per individual monograph

non-official tests
• hardness test
• Friability test

Packaging and storing of tablets
Before tablets are sent out for distribution, they
are usually packaged using
packaging materials. The type of
appropriate
packaging
material used is a matter of choice and is
dependent on several factors including:
• The degree of protection required
• Compatibility of the packaging material
with the formulation.

TABLET COMPRESSION MACHINES
There are following 2 types,
i. SINGLE PUNCH/SINGLE STATION/ECCENTRIC PRESSES
ii. MULTI-STATION/ROTARY PRESSES
 SINGLE PUNCH/SINGLE STATION/ECCENTRIC PRESSES
 Single punch tablet press also known as eccentric press or single station press is the
simplest machine for tablet manufacturing.
 This machine uses single set of station tooling (a die and a pair of upper and lower
punches).
 The compaction force on the fill material is exerted by only the upper punch while the
lower punch is static such action equivalent to hammering motion and as a result, the
single punch press is referred to as stamping process.
 The single punch tablet press usually produces about 60-85 tablets/min.

WORKING MECHANISM OF SINGLE PUNCH MACHINE
The working cycle is as follows
i. FILLING
ii. WEIGHT ASDJUSTMENT
iii. COMPRESSION
iv. EJECTION
FILLING:
 Upper punch is withdrawn from the die by the upper cam, bottom punch is low in the die so powder falls in through the
hole and fill the die.
WEIGHT ASDJUSTMENT
 Bottom punch move up to adjust the powder weight, it raises and expel the extra powder.
COMPRESSION:
 Upper punch is driven into the die by upper cam.
 Bottom punch is raised by lower cam. Both punch heads pass between the heavy rollers to compress the tablet.
EJECTION:
 Upper punch is withdrawn by the upper cam. Lower punch is pushed up and expel the tablets.
 Tablet is removed from the die surface by the surface plate.

TYPES OF SINGLE PUNCH MACHINE
The different series of the single punch tableting machine includes,
i. Automatic Single Punch Tableting Machine
ii. C&C600B Series Single Punch Tablet Press
iii. TDP - Benchtop Model Single Punch Tablet Press
iv. TDP-1 Benchtop Model Single Punch Tablet Press
v. TDP-5 Benchtop Model Single Punch Tablet Press
vi. TDP-30 Benchtop Model Single Punch Tablet Press

Automatic Single Punch Tableting Machine
 This machine is designed for pressing tablets from a variety of materials for Research & Development and
for small-scale production of Neutraceuticals,herbals, and other products.
 It is designed for pressing round tablets from various granular materials.
This is a bench-top unit, semi-portable, that is motor-driven but can also be hand-driven for adjustment and
testing purposes.
 One punch & die set is included. Fill depth, tablet thickness, and punch pressure are all adjustable. This is
by far our most popular unit
 This machine compresses powdered granular materials into tablet form. It is adjustable, operator friendly,
easy to maintain, compact and light weight.

C&C600B Series Single Punch Tablet Press
 C&C600B Series Single Punch Tablet Press is an advanced machine with new structure.
 It is a continuous, automatic tablet machine used in many departments such as pharmacy, laboratory
which needs to make powder, and granular raw material into tablets.

TDP - Benchtop Model Single Punch Tablet Press
This is designed for pressing tablets from a variety of materials for small-scale
production of neutraceuticals, herbals, and other products.
 Features are same as that of automatic single punch tableting machine.

TDP-1 Benchtop Model Single Punch Tablet Press
 This is a bench-top press unit, semi-portable.
One punch and die set is included.
 Fill depth, tablet thickness, and punch pressure are all adjustable.
This is a new unit, a little heavier-duty than the TDP Benchtop Press.

This is a heavy-duty benchtop unit.
 It produces tablets up to 20 mm in diameter.

 This is an extra heavy-duty benchtop unit.
 It produces tablets up to 24mm in diameter.
 Featuring precision filling, low-noise, low-consumption of material, and smooth operation.
 The minimum consumption of lab material is just 200g.
 It is reliable and efficient for research and development labs and small scale production.

PARTS OF A SINGLE PUNCH TABLET PRESS
Hopper: It is used to hold the materials (drug or the drug with excepients/
granules) to be compressed and supply the material to the die and removes the
tablet after its compression
Dies: Dies defines the shape and the size of the tablet by allowing the lower and
upper punch to come close together to compress the material.
Lower and upper punches: These are used for compressing of the materials
(drug or thedrug with excepients/ granules) within the dies.
Cam track: This is the component used for guiding the movement of thepunches.
Capacity regulator:To adjust the position of the lower punch to accommodate
the required quantity of materials by the die.
Ejection regulator: To adjust the position of the lower punch, so that its highest
position is at par with the surface of the die.
Driving wheel: It helps in the movement of the lower punch, the upper punch and
hoppershoe and also check their movement.

PARTS OF A SINGLE PUNCH TABLET
PRESS

ADVANTAGES OF SINGLE PUNCH TABLET
PRESS
The single punch structure is rational and small.
Easy to operate and it operates at a high utilization ratio.
It can manufacture odd shaped products with a diameter of up to 20mm.
It is ideal for development of tablets and small batch production.
Single punch tablet press utilizes a high amount of pressure to reduce weight
variations between tablets while maintaining a low noise level at the same time.

TYPES OF COMPRESSION MACHINES
MULTI-STATION/ROTARY PRESSES
Multi-station press is a mechanical device that unlike the single punch tablet press has
several tooling station which rotates to compress granules/powder mixture into tablets of
uniform size, shape (depending on the punch design) and uniform weight.
It was developed to increase the output of tablets.
 In rotary press, the compaction force on the fill material is exerted by both the upper and
lower punches leaving the powder granules to be compressed in the middle.This is known
as accordion type of compression.
The capacity of a rotary tablet press is determined by the rotation speed of the turretand
the number of stations on the press.

PARTS OF A ROTARY PRESS
 HOPPER
 FEEDER SYSTEM
 PUNCHES
 DIE SYSTEM
 TURRET
 CAM TRACKS
 TABLET PRESS FILLING STATION & WEIGHT CONTROL
 COMPRESSION ROLLERS
 EJECTION CAM
 TAKE OFF BLADE AND DISCHARGE CHUTE
 TOUCH SCREEN CONTROL PANEL
 SEALING SYSTEM
 ELECTRIC MOTORS,GEARS AND BELTS
 LUBRICATION SYSTEM
 HYDRAULIC PUMP UNIT

TABLET PRESS HOPPER
 The tablet compression process starts from here.
 Hopper is basically a material feeding section.
 It is the point where we put all powder/grains intended to compress into tablets.
 Tablet press hoppers come in a wide range of shapes and designs. Whatever the shape, it should be such
that the material can flow seamlessly into the tablet compression chamber.
 Since it is in direct contact with the material, it is made of stainless steel.
 Depending on the design of a tablet press machine, powder can be filled manually or using other
automated systems.
 Hoppers may feature optimal flow angles to facilitate flow, especially where it is nearly impossible to adjust
formulation.
 Some hoppers may have feature vibratory rods.This is done carefully to enhance product flow and to
prevent possible product separation.

TABLET PRESS FEEDER SYSTEM
Feeders feed powder/grains to the dies.
Tablet press machine feeder system is made up two criticalcomponents,
i. FEEDER HOUSING
ii. FEED PEDDLES
 FEEDER HOUSING
 Material from the hopper will enter the dye system through thehousing.
 The feeding process should be consistent and accurate to produce high quality tablets.
 The feeder housing is made of stainless steel 316L since it is in contact with the product.
 The product must not stick on the feeder housing as it will cause inconsistencies during the feeding process.
 FEED PEDDLES
 Number of high speed rotary tablet press machines have a feedpeddles.
 The feed peddles ensures consistent and accurate material feeding into the die systems.
 Without a feed peddle, especially if the machine is operating at a high speed, there could be chances of some dies being filled half way.
This may result in tablets with varying thickness or the degree ofcompaction.

TABLET PRESS PUNCHES
To produce the desired tablets, punches move within the die, thereby compressing powder into the
desired tablets.
In any tablet press machine, it has Upper punch system, the tablet press upper punches are on
the upper section of the rotary system. They move vertically, in and out of the diebore.
The lower punches are on the lower section of the rotary system of the tablet press machine.
During the tablet compression process, the lower punches remain within the die bore throughout
the entire cycle.
TABLET PRESS DIE SYSTEM
To produce the desired tablets, punches move within the die, thereby compressing powder into the
desired tablets.
The movement of tablet press machine punches, takes place within the die bore or cavity.
Therefore, the punch and die must be machined together to ensure compatibility.
It is in the die cavity where the powder is compressed into desired tablets of definite thickness and
size.
It is the die cavity that determines both the thickness and size of a tablet.

TABLET PRESS TURRET
 A rotating turret is an essential part of the rotary tablet press machine in the pharmaceutical industry.
 The rotating turret have holes that host the die system of a tablet making machine and punch guides to hold
punches
 It is precisely machined to ensure both die pockets and punch guides are fully aligned for optimal tablet making
process.
 Turrets are the heart of tablet press tooling.
 It is the tablet press machine turret that determines the number of stations.
 This helps to determine the production capacity of the machine for every complete rotation of the turret .

TABLET PRESS CAM TRACKS
 Cam tracks are critical tablet compression machine parts that play an integral role in ensuring seamless tableting process.
 The main work of the cam tracks is to guide the upper and lower punches in different stages in the tablet compression
process.
 That is, as the turret rotates, it is the cam trucks that move the punches in an up and down motion.
 This helps to control filling, compression and ejection of already processed tablets.
 For example, as the upper cam withdraws top punches from the die, powder flows in filling the cavity .On the other hand,
the lower cam track pushes the bottom punches upwards within the die cavity. This makes the die to be overfilled by
material, allowing for accurate adjustment of the die content.
 To achieve a maximum compression force, the upper cam track drives the top punch and the lower cam adjusts the bottom
punch. With the tablet compressed to the desired specifications, the upper cam withdraws top punches. On the other hand,
the lower punches move upwards to expel the compressed tablets with the help of lower cam.

TABLET PRESS FILLING STATION & WEIGHT CONTROL
 With the help of different movements of the cam systems, material will flow into the die cavity depending
on the position of the punches.
 A critical procedure in tablet compression process is the Weight control by controlling the depth of dye
filling.
 With the help of lower cam track, the bottom punch moves upwards to a predetermined height.
 This ensures the die cavity is filled to a required depth according to required weight of tablet before any
compression process begins.
 At this time as the bottom punch moves up, the excess powder may overflow. Therefore, to avoid
wastages, the excess powder automatically moves to the next die cavity, which is just about to be filled.

COMPRESSION ROLLERS
 Tablet compression machines have a series of rollers that exert a sufficient amount of force to compress the powder.
 Most machines have two sets of rollers.
PRE-COMPRESSION ROLLERS
 These are the very first rollers in rotary tablet press.
 Basically, these rollers apply a small amount of force on the upper and lower punches. This gives the initial compression
force.
 The aim of this process is to remove entrapped air that could be in the die or powder particles.
MAIN COMPRESSION ROLLERS
 Main compression rollers exert a predetermined amount of force (final compression force) for the formation of tablets. The
compression force at this stage is higher than the pre-compression force.
 It is important that the rollers remain stable with no vibration during the entire process. This is to ensure consistency of
the tablets’ thickness and size.

TABLET PRESS EJECTION CAM
 Ejection cam is located just after the main compression rollers.
 After compression, the tablet is always fixed within the die systems (space between lower and upper
punches).
 The ejection cams steadily and slowly push the bottom punch upwards. At the same time, the top cams
move up and so are the top punches .As a result, the fully compressed tablets leave the die cavity i.e. the
compressed tablet remains just at the top of the die.
TAKE –OFF BLADE AND DISCHARGE CHUTE
 The take –off blades are fitted just above the feeder housing.
 Their main role is to deflect the fully compressed tablets into the discharge chute and then are collected in
containers.

TOUCH SCREEN CONTROL PANEL
 HMI system control every aspect of the tablet making process.
 HMI can either be attached to the main machine or exist separately.
SEALING SYSTEM
 The sealing system provides advanced dust handling capability. This isolation reduces need to clean the
machine regularly and possible cross contamination.
ELECTRIC MOTORS, GEARS AND BELTS
 The compression rollers, punches, dies, turret, etc. are all moving parts. This means that the machine
uses a prime mover.
 We can use a servo motor or an induction motor. For example, a servo motor is a perfect choice for the
filing system. This is because it is easy to control servo-motors to meet the highest degree of precisions
such as 0.01mm.
 However, for the pre-compression and compression stages, synchronous motors offer a better speed
and control. Servo motor for tableting machine Furthermore, to transmit this motion to other sections, we
may use a combination of both gears and belts. Even the motor can accurately start this machine,
whether under maximum load or with no load. In short, to achieve a desired motion, we need to
incorporate mechanical, hydraulic and electrical systems.

LUBRICATIONS SYSTEMS
 Moving parts form integral sections of tablet compression machine parts, therefore, to avoid wear and
tear due to friction, we need to lubricate moving parts.
 A number of tablet press machines feature a central lubrication system. The machines automatically
lubricate moving components.·
HYDRAULIC PUMP UNIT
 An efficient hydraulic pump unit will help maintain consistent pre-pressure and main pressure.
 This guarantees smooth and accurate tableting process.
 Internal section of a tablet press machine part again, to avoid possible damage that may occur on the
tablet press tooling system, these machines are equipped with an overloading protective unit.
 This automatically stops the machine in case of overload.
Other parts of the machine include,
 Rubber wheels (depending on the size of a machine), switches, LED light indicators, lockable
polycarbonate cabinet and cooling system.

ADVANTAGES OF ROTARY PRESS
High productivity can be gained with a minimal amount of labor while
saving money.
Rotary press has an output of between 9000 – 234000 tab/hour or more
thus saves time and meets up with the high demand of tablet dosage form.
The powder filled cavity can be automatically managed by a moving feeder.
Rotary press decreases waste of valuable formulation in non-specific
tablets.
The machine allows independent control of both weight and hardness.

PRINCIPLE OF TABLET COMPRESSION
MACHINE
PRINCIPLE
 In the tablet compression machine main principle is compressing the grains/powder in upper and
lower punch in a die hole.
The hydraulic pressure plays a key role.
This pressure is transmitted unreduced through the static fluid.
 Any externally applied pressure is transmitted via static fluid to all the direction in same
proportion.
 It also makes it possible to multiply the force as needed. If we increase the hydraulic pressure
more compressing force on tablet then it becomes more hard.

STAGES OF TABLET COMPRESSION
PROCESS
i. FILLING
ii. METERING/WEIGHT ASDJUSTMENT
iii. COMPRESSION
iv. EJECTION
FILLING
 The filling stage of tablet compression process involves transfer of granules to the compressing machine
punch-die cavity.
 The punch die cavity is composed of upper punch, die and lower punch. The position of lower punch
within the die determines the volume of the punch-die cavity.
 This volume must be appropriately sized for the weight of granulation to be compressed into tablets.
 The granulation is overfilled on the die table (turret) to ensure complete filling of the punch-die cavity
volume.

STAGES OF TABLET COMPRESSION PROCESS
METERING/WEIGHT ASDJUSTMENT
 The metering stage of the tablet compressing process involves removal of excess granulation from the compressing machine.
 This stage enables the exact weight (volume) of granulation to be compressed into tablets.
 The exact weight of granulation is controlled by the height of the lower punch in the die. The height of the lower punch is
controlled by the metering cam (also called the dosage cam).
 The lower punch is raised to the appropriate level in the die to provide the exact weight of granulation in the punch-die cavity.
The excess granulation is scraped from the surface of the die table.
COMPRESSION
 The compression stage of the tablet forms the tablet.
 This stage involves bringing together the upper and lower punches under pressure within the die to form the tablet.
 As the punches enter the compression stage, the upper and lower punches move between two large wheels called pressure
rolls. These pressure rolls push the punches together to form the tablet.
 The distance between the upper and lower punches determines the thickness and the hardness of the tablet. When the
punches are close together, a thin and hard tablet is created. When the punches are farther apart, the tablet made is softer
and thicker.
 The proper balance of thickness and hardness determines the optimum roll distance for any specific product. These
adjustments are made while keeping the tablet weight constant.

EJECTION
The ejection stage of the tablet compressing process involves removal of the tablet from
the lower punch-die station.
 In this stage, the upper punch retracts from the die cavity and rises above the turret table.
Then the lower punch rises in the die, which in turn pushes the tablet upward to the top
surface of the die table and out of the die cavity.
A scraper (also called takeoff scraper or tablet rake-off) then pushes the tablet off the die
table away from the compressing machine into the collection container through discharging
chute.

STAGES OF TABLET COMPRESSION
PROCESS

CLASSIFICATION OF MULTI- STATION PRESS
TOOLING
CLASSIFICATION OF MULTI-STATION PRESS
 The punches and dies is called tablet tooling that determines the shape, size and the identification markings of the tablets.
 The tooling must meet the specific requirements to satisfy the needs of dosage uniformity, production efficiency and
esthetic appearance.
 Internationally recognized standards for tablet compression tooling are asfollow,
i. TSM standard
ii. EU standard
TSM STANDARD
 TSM is acronym for the “TABLET SPECIFICATION MANUAL”, widely recognized and exclusive in the UnitedStates.
 TSM tooling specifications are the sole reference on U.S. manufacturing standards for tablets and tablet tooling.
 Established by the American Pharmacists Association (APhA).
 TSM tooling specifications are the only published standards for the tablet compression industry.
EU STANDARD
 EU, is short for “EUROSTANDARD” considered as the European standard and also globallyapplicable.
 EU, more widely used than the TSM.
 EU, or Euronorm standard tool configurations are not published or governed by any organization or association.
 The EU standard is the most common tooling configuration used outside the U.S.

DIFFERENCES BETWEEN TSM & EU
TOOLING CONFIGURATIONS
 The TSM punch head configurations have an angled top profile versus the domed head profile of EU
 The TSM punch inside head angle for “B” punches is 37° compared to the EU, which is 30°
 Overall head thickness is greater in both “B” and “D” configurations for TSM tooling specifications in comparison
to the EU spec
 The overall punch length of the TSM tool is 0.010 inches shorter than the EU

CLASSIFICATION OF MULTI -STATION PRESS
CLASSIFICATION OF MULTI-STATION PRESS.
Based on the standard of TSM and EU, tablet tooling is mainly classified
i. “B” TYPE TOOLING
ii. “D” TYPE TOOLING
“B” TYPE TOOLING
 The B tooling punches and dies can be further classified as BB.
 D tooling can also be used on B tooling machine that is call as DB
 The “B” type configuration has a normal, punch barrel diameter of 0.750in. (19mm).
 The “B” type can be used with two types of die or can be said to have two different die sizes:
 The “B” dies with a diameter of 1.1875in. (30.16mm), suitable for all tablet sizes up to the maximum for
the “B” punches.
 The smaller “BB” dies (small “B” die) that has a diameter of 0.945in. (24mm).
 This die type is suitable for tablets up to 9mm diameter or 11mm maximum.
 Machines that are designed to “B” type tooling exert a maximum compression force of 6.5 tones.

CLASSIFICATION OF MULTI-STATIONPRESS
“D” type
 This type has larger nominal barrel diameter of 1in. (25.4mm) and a die diameter of 1.500in. (38.10mm)
and thus is suitable for tablets with maximum diameter or maximum length of 25.4mm.
 Tablet press is designed to be used with either “B” or “D” tooling but not both. The compression force
obtainable in a machine depends on the type of tooling used.
 Machines that use the “D” type configuration exert 10 tones compression force.

TOOLING TERMINOLOGIES
COMPRESSION MACHINE PUNCH
HEAD
 The end of the punch that guides it through the cam track of tablet machine during Rotation.
HEAD FLAT (DWELL FLAT)
 The flat area of the head that receives the compression force from Rollers (in upper punches) and
determines the weight and ejection height (in lower punches).
OUTSIDE HEAD ANGLE
 The area gets in touch with the roller prior to head flat , while Compression.
INSIDE HEAD ANGLE
 This is the area, which pulls down the lower punches after ejection and lifts the upper punches after
compression.
NECK
 The relived area between the head and barrel, which provides clearance for the cams.

BARREL
 The area between neck and stem of punch.
 This area guides the punch (while going up and down) with reference to turret guides.
BARREL CHAMFER
 Chamfers at the ends of the punch barrel, eliminate outside corners.
BARREL TO NECK RADIUS
The area at junction of barrel and neck which provide smooth transition from barrel to neck.
BARRELTO STEM RADIUS
 The are at junction of barrel and stem which provide curved transition from tip length to barrel.
BARREL TO NECK CHAMFER
 The beveled area located between barrel and barrel to neck radius.
 The chamfer reduce wear to punch guide.

BARREL TO STEM CHAMFER
 The beveled area located between barrel and barrel to stem radius.
 The chamfer allows for the proper insertion of upper or lower punch into oil seal.
STEM
 The area of the punch opposite the head, beginning at the tip and extending to the point where
the full diameter of the barrel begins. If the chamfer is present the barrel usually reaches its full
diameter just above the chamfer.
TIP
 This determines size, shape & profile
TIP FACE:
 This area of punch is where the tablet is formed. Good surface finish is required here to get
quality tablets.
CUP DEPTH
 The depth of the cup from the highest point of the tip edge to the lowest point of the cavity

BAKELITE TIP RELIEF
 An undercut groove between the lower punch tip straight and the relief; it assures a sharp corner to assist
in scraping product adhering to the die wall; normally a purchased option for lower punches.
TIP RELIEF
 The portion of the punch stem which is a undercut or made smaller than the punch tip straight.
 Most common for lower punches to aid in reducing friction from the punch tip and die wall as the punch
travels through the compression cycle.
 the area where the punch tip and relief meet must be sharp to scrape product from the die wall as the
lower punch travels down for the fill cycle
TIP LENGTH
 The straight portion of the punch stem
TIP STRAIGHT
 The section of the tip that extends from the tip relief to the end of the punch tip; it maintains the punch tip
size tolerance.
WORKING LENGTH
 This distance between bottom of the cup and the head flat is called as working length which determines
weight and thickness of the tablet.

OVERALL LENGTH
 Distance between top of the cup and the head flat.
KEY
 A projection normally of mild steel which protrudes above the surface of the punch barrel.
 It maintains alignment of the upper punch for re-entry into the die, mandatory on upper punches with
multiple tips and all tablet shapes other than round.
 Commonly used with embossed round tablet shapes when rotation of the punch causes a condition
known as double impression
KEYANGLE
 The relationship of the punch key to the tablet shape. The keys position is influenced by the tablet
shape, take-off angle, and turret rotation.
KEY POSITION
 The radial and height position of a key on the punch barrel; not found in all presses .

DOMED HEADS
 Increases the dwell time and hence help to achieve the better tablet hardness.
DWELL TIME
 The time punches spends below the pressure roller while rotating in the machine.
LAND
 The area between the edge of the punch cup and the outside diameter of the punch tip; this adds
strength to the tip to reduce punch tip fracturing
MAJOR AXIS
 The largest dimension of a shaped tablet
MINOR AXIS
 The smallest dimension of a shaped tablet
Clearance:
 Die bore dia – punch tip dia = Clearance.

DIE TERMINOLOGY
DIE.O.D.
 The outside diameter of the die, which is compatible with the die pockets in the press.
DIE HEIGHT
 The overall height of the die.
DIE BORE
 The cavity where the tablet is made. The Cavity’s shape and size determine the same form oftablet.
CHAMFER
 Entry angle of the die bore.
TAPER DIES
 Dies with tapered bore on one or both sides isused.
 They are used for easy removal of entrapped air and easy ejection of tablets (mainly for double layered tablets).
DIE GROOVE
 The groove around the periphery of the die, which allows the die to be fixed in thepress.
LINED (INSERT) DIES
 Dies fitted with a linear insert made from a much harder, more wear resistant material such as tungsten carbide and
ceramic.

SHAPES OF PUNCHES/TABLET IN REGULAR USE
 Round
 GEOMETRIC
 CONVEX
 CONVEX & BEVEL
 OVAL
 MODIFIED OVAL
 CAPSULE
 MODIFIED CAPSULE
 COMPOUND CUP
 FLAT FACED
 FLAT FACED BEVEL EDGED
 FLAT FACED RADIUS EDGED
 DEEP CONCAVE (ROUND/CAPSULE)
 EXTRA DEEP
 MODIFIED BALL
 SHALLOW CONCAVE (ROUND/CAPSULE)
 STANDARD CONCAVE (ROUND/CAPSULE)

SHAPES OF PUNCHES/TABLET IN REGULAR
USE

SHAPES OF PUNCHES/TABLET IN REGULAR USE

SHAPES OF PUNCHES/TABLET
FLAT FACE (FF )
 Flat Face design is very simple.
 It cause a problem called edge attrition.
 The problem is created as the flat face tool entered into the compression cycle. The FF design naturally
push or force the powder to the outside perimeter of the punch tip and towards the die wall, which in turn
extrude through the punch and die clearance

FLAT FACE BEVEL EDGE
The FFBE was designed as an alternative to the Flat Face design.
FFBE solve the problem of edge attrition.
The FFBE deflect or guide the powder back into the tablet, hence reducing soft edges.
 Although the FFBE design proved to be beneficial for reducing soft edges, it presented a
new problem, which was punch tip failure.
 On an FF punch tip, there was virtually no cup or cup depth of the punch tip, it was
simply flat, so there was not a cup limiting compression force, pressure limits were
determined by the punch tip size to reduce tip bending and distortion.

FLAT FACE RADIUS EDGE OR FFRE
FFRE is an alternative to the FFBE tablet design.
 The FFRE is much more robust and has several advantages over the FFBE.
 Better uniform tablet hardness as the powder has a natural flow across the
radius, which can reduce hot spots and or discoloration to the perimeter of the
top of the tablet
Consumer acceptance as the FFRE tablet has a softer look and is more
appealing to the consumer and generally has a better mouth feel.

ADVANCE TOOLING DESIGNS
MULTIPLE TIP TABLET PRESS TOOLING
 These tools are common in high capacity tablet press machines.
 These can produce more than one tablet in every punching station.
 A multi-tip tool consists of three parts,
i. CAP THAT SERVES AS THE HOLDER FOR THE PUNCH TIPS.
ii. PUNCH BODY.
iii. INDIVIDUAL PUNCH TIPS.
 The replacement punches incorporate several punch tips and the replacement die has correspondingly
multiple holes enabling two or more tablets to be produced from a single compression stroke of the tablet
machine.
 Depending on the type of material and tablet press, up to 8 punch tips can replace a single conventional
punch tip. Such modification therefore enables 8 tablets to be produced for every compression stroke of the
tabletting machine

MULTIPLE TIP TABLET PRESS TOOLING
BENEFITS
 Increase in productivity, number of tablets per turret rotation is multiplied by the number of tips.
 No large capital outlay on new tablet presses mean that higher tooling costs are easily outweighed
by increased output.
 Reduction in press run-time per output of tablets means that less maintenance is required per
batch of tablets produced.
 Reduction in press setup-time per output of tablets.
 Less tablet presses required to satisfy output therefore requiring less floor space leading to more
product produced per square meter.
 All of the above lead to reduction in overall plant running costs.

The following need to be considered when contemplating the installationof
multi-Tip punch tooling:
 The upper section of the turret must have keyways. This ensures the correct fixing of the upper punch.
 Modification to the feeder paddles may be required due to increased fill requirements
 Tablet press monitoring systems can be adjusted to monitor the multitablet outputs as standard.
 Granulation flow must be working effectively due to the increased fill requirement
 The tablet press should be in good working order and critical dimensions of the turret (punch guides and
die pockets) should all be within accepted tolerance.

ROTATING HEAD PUNCHES/ROTAHEADS
The rotating head has two-parts ,
i. THE HEAD OF THE PUNCH
ii. KEYED PUNCH BODY
 The head of the punch rotates independently to the keyed punch body.
 This creates increased contact surface area between the cam and punch head.
 Back angle aging is therefore drastically reduced, allowing for less head wear and
longer punch service life.
 Dwell time is also increased.

QUICK RELEASE TOOLING
 For use with R&D tablet presses, Quick-Release Tooling allows to quickly change punch head configurations,
to determine the ideal dwell time for a tablet formulation.
 Quick Release Tooling Station Comes With,
i. ONE PUNCH BARREL.
ii. THREE INTERCHANGEABLE HEAD CONFIGURATIONS (DOMED, EXTENDED FLAT DOMED, AND FULL RADIUS)
iii. ONE CUSTOMIZED PUNCH TIP.
 It save both time and money.
 Determine the ideal production dwell time before scale-up without changing turret speed by easily and quickly
changing punch head configurations.
 Eliminate the time and labor required to replace multiple sets of tooling during the R&D process and the cost
of purchasing multiple sets of tooling
 Perform a detailed analysis of a formulation’s compressibility as well as greater troubleshooting capacity in
the early stages of tablet development.

QUICK RELEASE TOOLING

CERAMIC BARREL OPTION:
Requires no lubrication
Less wear, less friction, and less heat buildup
Absorbs less heat from surrounding metals
Will not expand due to heat
Reduces potential for tooling binding

LINED DIES
 Lined dies, commonly called insert dies, are used specifically to compress abrasive and corrosive
formulation.
BENEFITS OF LINED DIES
 Increased tool life.
 Less head wearing.
 Reduced friction.
 Elimination of corrosion.
 Extended tablet quality.
CARBIDE LINED DIES
 Recommended with abrasive granulations.
 Work well for neutraceutical applications.
 Provide a high level of wear resistance during the compression of abrasive products.
 Increase die life by more than 10 times due to their wear liner.

CERAMIC LINED DIES
 Recommended for corrosive products
 Reduce the coefficient of friction throughout tablet compression cycles
 Available for round and shaped tablets
 Include a wear liner that prevents them from wearing
 Increase die life by 5-10 time

DIAMOND COATING
 The idea here is to introduce properties of diamond to a punch and die system.
 Such tools are suitable for effervescenttablets.
 Diamond coated tools are generally abrasive resistant anddurable.
 They don’t stick and their hardness is nearly 6 times more than the ordinarytablet presses.
GALVANIC CHROME TREATMENT
 This tablet press tooling is suitable for most standard tablet press applications.
 In most cases, the coating is about 5microns.
 The coating is one of the most popular types of treatment in most pharmaceuticalindustries.
 This protects the tooling system of a tablet compression machine from wear and ensures better stability.
CHROME NITRIDE COATING
 The final surface of the tablet press tooling is better than the galvanic treatment.
 It has a high quality to price ratio with enhanced wearprotection.
ALUMINUM TITANIUM NITRIDE OR TITANIUM NITRIDE COATING
 This treatment is known for its smooth finish and higher surfacehardness.
 Therefore, it is a perfect choice for most pharmaceutical tablet compression applications.

INTERCHANGEABLE TURRET
 It allows tool free operation and dramatically reduced product change over.
 Faster product to product change over.
 Easier production planning and preparation as machine turrets can be made ready in advance.
 The ability to clean to a higher standard and offline.
 Configure the machine to maximize output through optimum tooling to product size selection.
 The precision drive coupling gives the strength of a fixed turret machine, so make tablets up to
100KN.
 Improved engineering access over fixed turret machines.
 Keep the initial investment down by buying the different turret sizes at a later date

SEGMENTED DIE TABLE
 Die table segments are engineered to eliminate the need for individual dies and die lock screws.
 The design increase production by up to 25% and make process simpler and smoother.
 With Die table segments gain more die stations per turret/press.
 Enhance productivity.
 Decrease set-up time by as much as 88%.
 Without the need for dies and die lock screws, efficiency will skyrocket, providing a more
productive process overall.
 In addition to providing optimum tablet production it reduce downtime for refitting, resetting, and
cleaning.
 Segments can be changed by loosening just two fastening bolts and only between 3 to 5
segments are needed for each turret, depending on the type of tablet press.

SEGMENTED DIE TABLE

BENEFITS OF SEGMENTED DIE TABLE
 Reduced product loss.
 Easier compliance with hygiene requirements.
 Up to 40% more output.
 Great production reliability through easy refitting.
 Service life increased by up to threefold through carbide brushes.

Reference
 Adolfsson, Å., Caramella, C., Nyström, C., 1998. The effect of milling and addition of dry
binder on the interparticulate bonding mechanisms in sodium chloride tablets. Int.J.
Pharm. 160, 187-195.
 Adolfsson, Å., Gustafsson, C., Nyström, C., 1999. Use of tablet tensile strength adjusted
for surface area and mean interparticulate distance to evaluate dominating bonding
mechanisms. Drug Dev. Ind. Pharm. 25, 753-764.
 Adolfsson, Å., Nyström, C., 1996. Tablet strength, porosity, elasticity and solid state
structure of tablets compressed athigh loads. Int. J. Pharm. 132, 95-106.
 Stahl H, Areview article on latest process advancements and innovations in
Granulation technology.
 Yadav V
. B., YadavA. V., Liquisolid granulation technique for tablet
manufacturing: an overview in Journal of Pharmacy Research.
 Malcolm Summers, Michael Aulton, a review on Granulation.
 Niro pharma system on current issues and troubleshooting fluid bed
granulation,may1998.
 Harald Stahl,Senior pharmaceutical technologist, GEAPharma Systems,
Germany
 Detlev Haack . Hermes Arzneimittel GmbH – Division Hermes Pharma,
Grosshesselohe (Germany).

REFERENCES
 Aulton, M. E. (2007). Alton'spharmaceutics: The design and manufacture of
medicines.
 Edinburgh: Churchill Livingstone.
 Pharmaceutical dosage forms: Tablets. Vol.I.Edited by HH Lieberman ...
 Keith marshall 1987,Compression and consolidation of powderd solids, Leon
lachman, Herbert a.Liberman, & Joseph kanig ,The theory and practice of industrial
pharmacy, third edition varghese publication house,bombay, pp.66,68,70-88.
 Eugene parrott , 2007,Compression,Herbert A.Liberman, Leon Lachman & Joseph
B.Schwartz ,Pharmaceutical dosage forms, tablets, volume ii,pp.201-241.
 Stanforth J.N,Aulton’s pharmaceutics the design and manufacturing of
medicine,third edition,Churchill livingstone elsevier,pp.176,177.
 Subrahmanyam C.V. ,Micromeritics, Textbook Of Physical Pharmaceutics, Second
Edition,vallabh prakashan,delhi,Pp-180-234.
 Gilbert S. Banker , Christopher T. Rhodes, Modern
Pharmaceutics , Fourth Edition.Pp.408-409.
 encyclopedia of pharmaceutical Technology, Second
Edition,volume- 3.Pp.303-305

References
 Text book of Physical Pharmacy ByAlbert Martin.
 www.google.com.
• The theory and practice of Industrial pharmacy, by Leon Lachmann and
Herbert A.Lieberman,3rd edition, Page no: 294 to 336.
• The science and practice of pharmacy by Remington, Volume I, Page no:
905 to 916.
• Indian pharmacopoeia 2010, volume-2, Page no: 751 to 754.
• www.wikipedia .com

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