SEMINAR TOPIC: COMPRESSION PHYSICS IN FORMULATION

DEVELOPMENT OF TABLETS

SUBJECT: MODERN PHARMACEUTICS

SUBJECT CODE: PHTCH012

PREPARED BY: SHASHANK H. BHANDARI

ID NUMBER: 22MPHTCH010

DEPARTMENT OF PHARMACEUTICS, MPHARM 1st YEAR

GUIDED BY: DR MRUNALI PATEL, PROFESSOR, DEPARTMENT OF

PHAMCEUTICS, RAMANBHAI PATEL COLLGE OF PHARMACY-
CHAROTAR UNIVERSITY OF SCIENCE AND TECHNOLOGY

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 Contents

 Introduction

 Compression, compaction and consolidation

 Properties of powders/granules

 Manufacturing of granules

 Stages of compaction

 Process of compression or compression cycle

 Forces involved in compression

 Tablet compression machine

 Properties of tablets influenced by compression

 Force of distribution

 Equation for compression study

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 Introduction

 Tablet is a unit solid dosage form, due to high precision, dosing,

manufacturing efficiency and patient compliance make tablet to most
popular dosage forms. Compression and compaction are the duet
constitutive parts of tablet manufacturing.

 Mechanistic aspects of tableting can be studied using several theories like

mechanical theory, intermolecular theory, and liquid surface film theory.
These all parameters have potential importance in various pharmaceutical
research and development.

 Tablets are made by compressing a drug or drugs with excipients on

stamping machine called presses. Tablets presses are either single punch or
multi station rotary presses.

 Different excipients used during the tablet manufacturing process are

diluents, disintegrants, lubricants, antiadherents, glidents, colors, flavors,
sweeteners, binders etc.,

 Compression, compaction and consolidation are importance concepts to

understand the tablet manufacturing

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 Compression, compaction and consolidation

 Compression: Compression of a powder means reduction in the bulk

volume of a material as a result of displacement of the gaseous phase under
pressure.

 When an external forces are applied to the powder mass, there is a normally
reduction in its bulk volume as a result of one or more effects like
deformation, rearrangement, repacking etc.,

 Compaction: Compaction of a powder is a general term used to describe a

situation in which powdered material is subjected to some level of
mechanical force.

 The physics of compaction may be simple stated as “the compression and

consolidation of a two phases (particulate soli-gas) system due to the applied
force.

 Consolidation: Consolidation is defines as an increase in the mechanical

strength of a material resulting from particle-particle interaction.

 Consolidation process: When the surface of two particles approach each

other closely enough, (e.g. at separation of less than 50nm) their free surface
energies result in strong attractive forces, this process known as cold
welding.

 Contact of particles a multiple points upon application of load, produces

heat which causes fusion or melting. If this heat is not dissipated, the local
rise in temperature could be sufficient to cause melting of the contact area of
the particles. Upon removal of load it gets solidified giving rise to fusion
bonding and increase the mechanical strength of mass.
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 Properties of powder/granule

 While studying physics of compression considering following factors:

 Angle of repose (Φ): Angle of repose (Φ) is the maximum angle between
the surface of a pile of powder and horizontal plan. It is usually determined
by fixed funnel method and is the measurement of the flowability of
powder/granules.

 Φ= tan-1 (h/r)

H= heap of pile
R= radius of bas of pile

 Relation between angle of repose and type of flow:

Angle of repose Type of flow

<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor

 Bulk density: The bulk density is the ration of the mass of an untapped
powder sample and its volume including the contribution of the
interparticulate void volume.

 Hence, the bulk density depends upon both the density of powder particles
and spatial arrangement of particles in the powder bed.

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 Bulk density of powder is determined by graduated cylinder method based
on tapping the powder from 1 inch height thrice in 2 min interval.

 Tapped density: The tapped density is an increased bulk density attained

after mechanically tapping a container containing the powder sample.

 The tapped density is obtained by mechanically tapping a graduated

measuring cylinder or vessel containing the powder sample.

 The tapped density is a very popular measure for powder characterization

because of both the simplicity and the rapidity of the measurement. The
ability of a powder sample to pack under taps gives a measure of the powder
cohesiveness which can be linked to its flowability.

 Hausner ratio: Hausner ratio is defined as the ratio of a powder’s tapped

bulk density to its bulk density.

 This ratio can be applied to provide an index of the flow character of a

powder.

Hausner ratio Type of Flow

Less than 1.25 Good flow
1.25-1.5 Moderate
More than 1.5 Poor flow

 Carr’s index: Compressibility is the ability of powder to decrease volume

under pressure. Compressibility is a measure that is obtained from density
determinations.

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 % Compressibility or Carr’s index= (Tapped bulk density- poured or u or
aerated Bulk density/ tapped density) × 100.

 Compressibility measure gives idea about flow property of the granules as

per CARR’s index which is as follows:

Carr’s index ( % compressibility) Flow description

5-15 Excellent- free flowing granules

12-16 Good- free flowing powder granules

18-21 Fair powder granules

23-28 Poor- very fluid powder

28-35 Poor- fluid cohesive powder

35-38 Very poor- fluid cohesive

>40 Extremely poor- cohesive powder

 Porosity: Porosity is a key attribute of tablets that can strongly influence

their performance by measuring porosity, the manufacturer can design
tablets to satisfy critical parameters including:

 Deformation properties during compression, pharmacokinetic behavior,

shelf life, moisture ingress during dissolution, the bioavailability of the
active component, the dissolution rate of tablet.

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 Porosity is a good prediction of how liquids enter into the tablet matrix and
the expectations can be validated by experiment.

 The porosity is defined as the ratio of the void volume to bulk volume.

 True volume= volume of powder itself

Granule volume= volume of powder itself plus the volume of intra-particle
space/pore
Bulk volume= volume of powder itself plus the volume of intra-particle
space/pore plus volume of inter- particle space (void).
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 So, Void volume (Vv)= Bulk volume (Vb) – True volume (Vt)

Porosity= Vv/Vb
= (Vb- Vt)/ Vb
= (1- Vt-Vb) ×100

 Tablet porosity is not just a predictor of dissolution and solvent ingress.

With the growing importance of quality by design porosity is also an
important critical quality attribute for both disintegration and bioavailability
properties. These parameters are vital to provide data to allow the prediction
of API and excipients behavior in formulation.

 The physical properties of granules and their porosity are generally excellent
influencers of compatibility that can be adjusted during the manufacturing
process by modifying the formulation. Changes in porosity or compression
shear strength are extremely significant in the compaction characteristics of
granules.


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 Manufacturing of granules

 The manufacture of granulations for tablet compression may follow one or a

combination of 3 methods:

1) Direct compression: It is a popular process because it provides the shortest,

most effective and least complex to produce tablets. The manufacture can
blend an API with the excipient and lubricant, followed by compression; no
additional processing steps are required.

 There are a few crystalline substances such as sodium chloride, sodium

bromide and potassium chloride that may be compressed directly. Direct
compression materials, in addition to possessing good flow and
compressibility, must be inert, tasteless, rework able, able to disintegrate and
inexpensive.

2) Dry granulation: Dry granulation does not involve the use of a liquid
lubricating agent. This is because constituents utilized might chemically
react with the agent used, thus dry granulation equipment technique is used.

 In dry granulation process first API and excipients are mixed together
through dry mixing.

 After mixing of the materials, they are passed through roller powder
compactors for compaction. The results in the formation of slugs. Slugs are
rough form tablets, usually quite large in size.

3) Wet granulation: Active pharmaceutical ingredients (API) and excipients are

sifted, usually through a 40 mess or 60 mess sieve. When API and excipients
are sifted they mix together.

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 In order to mix them up more thoroughly, the dry mixing process is utilized.
Once the mixing is complete, granulating fluid is added to RMG.
 The materials are then dried in a dryer, usually a fluid bed dryer or a try
dryer. When the constituents have dried, they are then milled using 16 mess
or 20 mess sieves.

 The final step is lubrication in order to make the particles adhere firmly
together. This is done with the lubricating agent. The use of lubricating
agents is particular to the types of API and excipients used. The most
commonly used lubricating agent is magnesium stearate. The material
formed is thus ready for further compression and manufacturing.

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 Stages involved in Compaction

 The complete cycle of compaction occurs in four steps:

 Stage 1: Top 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 fills the die.
 Stage 2: Bottom punch moves up to adjust the powder weight. It raises and
expels the excess powder.
 Stage 3: Top punch is driven into the die by upper cam and bottom punch is
lowered by lower cam. Both punches heads pass between heavy rollers to
compress the powder.
 Stage 4: Top punch is withdrawn by the upper cam. Lower punch is pushed
up and expels the tablet. Tablet is removed from the die surface by surface
plate.

Process of Compression or Compression cycle

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 When some external forces applied on the powder reduction in the bulk
volume of the powder.

1. Particle rearrangement: Particle size distribution determines initial

repacking. During initial stage of compression, particle subjected to low
pressure, during this particles move with respect to each other and smaller
particles enters in voids between larger particles.

 As a result volume decreases and density increases spherical particle

undergoes lesser rearrangement than irregular particle.

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 The energy is evolved as result of interparticulate friction and there is an
increase in amount of particles.

Punch and Fines enters the Rearrangement

particle at low voids of larger occurs
pressure particles

Force applied

2. Deformation: When powdered mass is subjected to pressure, there is finite

change in geometry depending upon intensive operation. It depends on
physical properties of the material as well as the amount of compaction force
applied.

 Energy lost during this process. As the load increases, however,

rearrangement becomes difficult and further compression involves some
types of particle deformation.

 Deformation can be three types: a) Elastic deformation, b) Plastic

deformation, c) Brittle fracture.

 a) Elastic deformation: If on removal of the load, the deformation is to

large extent spontaneously reversible that is if it behaves like rubber, then
the deformation is said to be elastic.

 With several pharmaceutical materials, such as acetylsalicylic acid and mcc,

elastic deformation becomes the dominant mechanism of compression
within the range of maximum force normally encountered in practice.

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 Elastic deformation:
Force

 B) Plastic deformation: In other groups of powdered solids, an elastic limit

or yield point is reached and loads above this level result in deformation not
immediately reversible on removal of the applied force.

 Bulk volume reduction in these cases results from plastic deformation and/or
viscous flow of the particles, which are squeezed into the remaining void
spaces, resembling the behavior of modeling clay. This mechanism
predominated in materials in which the shear strength is less than the tensile
or breaking strength.

 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.

 Plastic deformation:

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 Brittle fracture: When the shear strength is greater, particles may be
preferentially fractured and the smaller fragments then help to fill up any
adjacent air space. This is found likely to occur with hard, brittle particles
and in fact is known as brittle fracture; sucrose behaves in this manner.

 The predisposition of a material to deform in a particular manner depends on

the lattice structure; in particular whether weakly bonded lattice planes are
inherently present.

3. Fragmentation: Fracture occurs when the stress within the particle become
great enough to propagate.

 Fragmentation causes further densification with the infiltration of the smaller

fragments into the void space

 With some materials fragmentation doesn’t occur because the stress is

released by plastic deformation.

4. Bonding: After fragmentation of particles, as the pressure increases,

formation of new bonds between the particles at the contact area occurs.

 The mechanical strength of a tablet depends on the dominating bonding

between the particles and the surface area over which these bond act.

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 When the surface of two particles approaches each other closely enough,
their surface energies result in a strong attractive force, a process called cold
welding.

 The mechanical theory: If only the mechanical bond exist, the total energy of
compression is equal to the sum of deformation, heat and energy absorbed
for each constituent.

 The inter-molecular theory: The molecules at the surface of solid have

unsatisfied forces, which interact with the other particles in the true contact.

 The liquid surface file theory: Bonding to the presence of a thin liquid film
which may be consequence of fusion or solution at the surface of the particle

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 induced by the energy of compression. It may classified into two ways:1)
Hot welding, 2) cold welding

 1) Hot welding: On macro scale, irregular particle shape, there are a number
of points of contact. Application of load under appreciable force, results in
generation of frictional heat. If this heat is not dissipated, local rise in
temperature.

 This heat is sufficient to melt the contact surfaces. Melt solidifies gives rise
to fusion bonding, which results in increasing mechanical strength of tablet.

 2) Cold welding: Particles closely enough (>50nm) to each other their free
surface energies results in a strong attractive bond formation.

 This bond depends on interior nature of the particles. This phenomenon is

called cold welding. Cold welding results in increasing mechanical strength
of tablet.

5. Deformation of the solid body: Applied pressure further increased the

bonded solid; consolidated toward a limiting density by plastic and/or elastic
deformation of the tablet within the die.

 Strain: The relative amount of deformation produced on a solid body due to

applied force. It is dimensionless quantity. Compression strain,
Z= ∆H/ Ho where, H= thickness

 Stress: σ=F/A here, F is force required to produce strain in area A. As the

applied pressure is further increased, the bonded solid is consolidated toward
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 a limiting density by plastic and/or elastic deformation of the tablet within
the die

6. Decompression: The success and failure of intact tablet depends on stress

induced by elastic rebound and the associated deformation produced during
compression and ejection.

 As the upper punch is withdrawn from the die the tablet is confined in die
cavity by radial pressure consequently any cavity change during
decompression must occur in axial direction.

 Thus capping is due to unaxial relaxation in die cavity at the point where
punch pressure is released and some may occurs at ejection.

 If decompression occurs in all directions simultaneously capping is reduced.

7. Ejection: The lower punch rises and pushes the tablet upward there is
continued residual die wall friction. As the tablet removed from the lateral
pressure is relieved and the tablet undergoes elastic recovery with an
increased portion (2-10%) of the volume of that portion of the tablet
removed from the die.

 This process requires force in three phases:

 The force necessary to eject a tablet involves the distinctive peak force
required to initiate ejection, by breaking of die wall- tablet adhesion.

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 The second stage involves the force required to push the tablet up the die
wall.

 The final stage is marked by a declining force of ejection as the tablet

emerges from the die.

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 Forces involved in compression:

 Frictional forces: These are interparticulate friction and die wall friction
reduced by gildants (colloidal silica) and lubricants (Mag. Stearate)

 Radial forces and ejection forces: Radial die wall forces and die wall
friction also affects ejection of the compressed tablet form die. The
necessary to eject a finished tablet is known as Ejection force. Variation also
occurs in ejection force when lubrication is inadequate.

 The force necessary to eject a finished tablet follows a distinctive pattern of

three stages. The first stage involves the distinctive peak force required to
initiate ejection, by breaking of tablet/ die-wall adhesions.

 A smaller force usually follows, that required to push the tablet up the die
wall. The final stage is marked by declining force of ejection as the tablet
emerges from the die.

 Most pharmaceutical tablet formulations require the addition of a lubricant

to reduce friction at the die wall. Die wall lubricants function by interposing
a film of low shear strength at the interface between the tableting mass and
die wall

 There is some chemical bonding between this boundary lubricant and the
surface of the die wall as well as at edge of the tablet. The best lubricants are
those with low shear strength but strong cohesive tendencies in directions at
right angles to the plan of shear.

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 Tablet compression machine

 Tablets are made by compressing a formulation containing a drug with

excipients on stamping machine called as presses.

 The components of tablet machines are:

 Tablet Compression Machine Hopper. The feed hopper is where the process
begins.
 Tablet Press Die System.
 Tablet Press Punches.
 Tablet Press Turret.
 Tablet Press Machine Cam Tracks.
 Tablet Press Filling Station & Weight Control
 Compression Rollers
 Feeding mechanism

Punch and die Turret Cam-tracks

 Hopper: For holding of the granules

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 Dies: Define the size and shape of the tablet.

 Punches: For the compressing the granules with the dies.

 Cam tracks for guiding the movement of the punches.

 Feeding mechanism: Distribution of granules from the hopper into the dies.

 Single punch tablet compression machine

 Die filling: It is accomplished by gravitational force.

 Tablet formation: upper punch enters the die and powder is compressed.

 Tablet ejection: Lower punch rises until its tip reaches the level of top of the
die.

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 Multi station/ rotary compression machine:

 Multi station press is a mechanical device that unlike the single punch tablet
press has several tooling stations which rotates to compress granules/powder
mixer into tablets of uniform size, shape and uniform weight. It has
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 turret and the number of stations on the press.

 Components/ Functional parts of a rotary press:

 Hopper: The hopper holds the granules/powder mixture that is to be

compressed into tablets.

 Die cavity: This is where the powder granules are compressed into tablets
and it determine, the diameter of the tablet, the size of the tablets, to some
extent the thickness of the tablets.

 Feed paddle: Helps to force the feed into dies especially during faster
rotation.

 Punches: This comprises the upper and the lower punches. They move
within the die bore to compress granules into tablets.

 Lower cam track: This guides the lower punch during the filling stage so that
the die bore is overfilled to allow accurate adjustment.

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 Cam tracks: This guides the movements of both the upper and lower
punches.

 Pre compression rollers: This roller gives the granules an initial compression
force to get rid of excess air that might be entrapped in the die.

 Main compression rollers: This roller applies the final compression force
needed for the formation of tablets.

 Ejection cam: Guides the lower punch upwards facilitating the ejection of
tablets from the die cavity after compression.

 Discharge chute: This is where the tablet passes through for collection after
being deflected by the take-off blade.

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 Difference between single punch tablet press and rotary tablet press:

1) Single punch tablet presses utilize single-sided compression to make

tablets, whereas rotary presses use double-sided compression

2) Single punch tablet press compression cycles do not have a dwell time,
whereas rotary presses typically use a punch head flat which enables a dwell
time as the punch passes under the compression cycle.

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 Properties of tablets influenced by Compression

 Density and porosity

 Hardness and tensile strength
 Specific surface area
 Disintegration
 Dissolution

 Density and porosity: The apparent density of a tablet is exponentially

related to the compression pressure. Porosity and apparent density are
inversely proportional.

 Hardness and tensile strength: There is a linear relationship between tablet

hardness and the logarithm of applied pressure except at high pressure.

 The radial tensile strength is proportional to the applied pressure. For an

isotropic, homogenous tablet, the radial and axial tensile strength is equal.

 As applied pressure is increased, fragmentation results in a stronger, radial

tensile strength than axial tensile strength.

 Specific Surface area: Specific surface is the surface area of 1g of material.

As the relationship between applied pressure and apparent density is
independent of the material being compressed, the influence of starch on the
specific surface and porosity is not significant.

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 As the lactose granules, which were granulated by adding 10% starch paste,
are compressed, the specific surface is increased to a maximal value.

 Dissolution: Dissolution is more rapid as the applied pressure is increased.

Dissolution is showed as the applied pressure is increased.

 Dissolution is faster to a maximum, as the applied force is increased and

then a further increase in applied pressure slows dissolution. Dissolution is
showed to a minimum as the applied pressure is increased and then further
an increase in applied pressure speeds dissolution.

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 Force of distribution

 Most investigations of the fundamentals of tableting have been carried out

on single station presses or even on isolated punch and die sets in
conjunction with a hydraulic press.

 Most system work with force being applied to the top of a cylindrical
powder mass. This simple compaction system provides a convenient way to
examine the process in greater detail.

 More specifically, the following basic relationships apply.

F A= F L + F D

FA= Force applied to upper punch

FL= Force transmitted to lower punch
FD= Reaction at die wall

 Because of this inherent difference between the force applied at the upper
punch and that affecting material close to the lower punch, a mean
compaction force-FM has been proposed, where:

FM= (FA+ FL)/2

 FM offers a practical friction independent measure of compaction load,
which is generally more relevant than FA. In single station presses, where the
applied force transmission decays exponentially. A more appropriate
geometric mean force FG might be:

FG= (FA×FL)1/2

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 Equations for compression study

 Heckel equation: Heckel equation is based upon analogous behavior to a

first order reaction, where the pores in the mass are reactant.
Log1/E= KyP + Kr
Ky= material dependent constant, but inversely proportional to material yield
strength(S).
Kr= related packing stage (Eo)

 This relation may be established by measuring applied force (F) and

movement of punches during compression cycle and translating the data into
applied pressure (P), for a cylindrical tablet.

P= 4F/ΠD2

D= diameter of tablet

 The particular value of heckle plot arises from their ability to identify the
predominant form of deformation in a given sample. Materials that are
comparatively soft and that readily undergo plastic deformation retain
different degree of porosity, depending upon the initial packing of die.

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 This in turn is influenced by the size distribution, shape etc. of the original
particles. Heckel plots for such materials are shown by type”a”- sodium
chloride is a typical example.

 Conversely, harder materials with higher yield pressure values usually

undergo compression by fragmentation first, to provide a denser packing.
Label”b” shows heckle plots for different size fractions of the same material
that are typical of this behavior. Lactose is one such material.

 The two regions of the heckle plots are thought to represent the initial
repacking stage and the subsequent deformation process, the point of

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 intersection corresponding to the lowest force at which a coherent tablet is
formed.

 In addition, the crushing strength of tablets can be correlated with the value
of Ky of the heckle plot; larger values of Ky usually indicate harder tablets.
Such information can be used as a means of binder selection when designing
tablet formulations.

 Heckel plot can be influenced by the overall time of compression, the degree
of lubrication, and even size of the die, so that the effect of these variables
can also be studied.

 Another important factor in the use of all force-porosity relationships is that

for many formulations, there is relatively narrow optimum residual porosity
range that provides adequate mechanical strength, water uptake and hence ,
good disintegration characteristics.

 It is to the formulators advantage to identify this optimum range and be able

to predict compressing conditions needed to reach it.

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 Conclusion

 The physics of tablet compression gives knowledge of compatibility and

flow ability of pharmaceutical powder which is essential for formulation of
tablets.

 The tendency of material for plastic deformation, fragmentation and

elasticity could be expressed and are compared with different material.

 The bonding theories in tablet preparation are studied to increase the

strength of tablet.

 Compression and consolidation are important in tableting of materials.

 The importance of each will largely depend on the type of compact required
whether soft or hard and on the brittle properties of the materials.

 The particular value of heckle plot arises from their ability to identify the
prominent form of deformation in a given sample.

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 References

 Lachman, L. Lieberman, H.A. and Kanig, The Theory and Practice of

Industrial Pharmacy, Third Edition 1990; Page No 66-99.

 Sarsvat Patel and Arvind Bansal Compression Physics in the

formulation Development of Tablets, Critical Reviews in Therapeutic
drug Carrier Systems, February 2006

 Michel E. Aulton, Aulton’s Pharmaceutics The design and

manufacture of medicines, Third Edition Page No 468-473

 CVS Subramanyam, Textbook of Physical pharmaceutics, Page No.

224-227.

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