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
 Contents

 Introduction
 Properties of powder/granules
 Granulation process
 Stages of compaction
 Compression cycle
 Force of distribution
 Types of forces
 Equation for compression study
 Tablet compression machine
 Properties of tablet influence by compression
 Conclusion
 Reference
 Introduction

 Tablet is a unit dosage form.

Mechanistic aspects of tableting can be studied using theories like

mechanical theory, inter molecular theory and liquid surface
film theory.

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

machine called press. Tablet presses are either single punch or multi
station rotary presses.

 Compression, compaction and consolidation are importance concepts

to understand tablet manufacturing.
 Compression, Compaction, Consolidation

 Compression: Compression of powder means reduction in the bulk

volume of a material as result of displacement of the gaseous phase under
pressure.
 Compaction: It 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 “Compression and
Consolidation of two phases (particulate solid-gas) system due to some
level of mechanical force.
 Consolidation: Consolidation is defines as an increase in the mechanical
strength of a material resulting from particle-particle interaction. (Hot
welding and cold welding)
Properties of Powder/Granules

 While studying physics of compression

considering following properties:
 Angle of repose: It is the maximum angle
between the surface of a pile of powder and
horizontal plan.
 It is usually determined by fixed funnel
method and it is the measurement of the
flowability of powder/granules.
Angle of repose Type of flow
 Angle of repose Φ= tan (h/r)
-1
<25 Excellent
H= heap of pile 25-30 Good
R= radius of base of pile 30-40 Passable
>40 Very poor
 Cont…

 Bulk density: It is the ratio of the mass of

an untapped powder sample and its volume
including the contribution of the
interparticulate void volume.
 It depends upon density of powder and also
arrangement of particles in the powder bed.
 It is determined by graduated cylinder
method.
 It is expressed in kg/m3
 Cont..

 Tapped density: It is an increased bulk

density attained after mechanically
tapping a container containing the
powder sample
 It is obtained by mechanically tapping a
graduated measuring cylinder or vessel
containing the sample.
 It gives a measure of the powder
cohesiveness which can be linked to its
flowability.
 Cont…

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

density to its bulk density.

Hausner ratio Type of Flow

Less than 1.25 Good flow

1.25-1.5 Moderate

More than 1.5 Poor flow

 Cont…

Carr’s index ( % Flow description

 Compressibility: It is the ability of compressibility)
powder to decrease volume under 5-15 Excellent- free flowing
pressure. It is obtained from density granules

determinations. 12-16 Good- free flowing

powder granules
 % compressibility or carr’s index =
18-21 Fair powder granules
(Tapped bulk density- poured or 23-28 Poor- very fluid powder
aerated Bulk density/ tapped
density) × 100. 28-35 Poor- fluid cohesive
powder
 It gives idea about flow property of
the granules as per carr’s index. 35-38 Very poor- fluid
cohesive
>40 Extremely poor-
cohesive powder
 Cont…

 Porosity: Porosity is a key attribute of tablet that

can strongly influence their performance;
manufacture can design tablets to satisfy critical
parameters like deformation properties during
compression, shelf life, pharmacokinetic
behavior, bioavailability of active component etc.
 The porosity is defined as the ratio of the void
volume to bulk volume.
 Porosity= Vv/Vb
= (Vb- Vt)/ Vb
= (1- Vt-Vb) ×100
 Changes is porosity or compression shear strength
are significant in compaction characteristics of
granules.
Granulation Process

01 Dry Granulation

Wet Granulation 02

03 Direct Compression
Cont…

 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.
 Mainly excipients used during dry granulation- Diluents:
Mannitol,MCC,Lactose anhydrous, Alpha lactose monohydrate (hydrous),
Disintegrants: sodium starch glycolate, starch 1500, MCC.
 Cont…

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

pass, through a 40 mess or 60 mess sieve. When API and excipients are sifted they
mix together.
 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. Other excipients used in wet granulation are- Binder: IPA+ PVP,
HPMC, starch pastes (5-25%), Disintegrants: MCC, Starch USP
Cont..

 Direct compression: 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.
 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.
 Mainly used excipient used during direct compression- Disintegrants:
sodium alginate, Avicel PH 101, Diluents: Mannitol, sorbitol, Lactose.
 Stages of Compaction

 The complete cycle of compaction occurs in four

stages:
 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.
 Compression cycle or Process of Compression

Deformation 02
01 Particle
Rearrangement

06 03
Ejection Fragmentation

05 Deformation of 04
solid body and Bonding
decompression
Removal of pressure
 Particle rearrangement

Punch and
Rearrangement
particles at low
occurs
pressure

Finer particles
enters the voids of
larger particles
 Deformation

Elastic
Deformation deformatio
n state regains
Original

01 03
Original
state lost
02 04

Stress applied Removal of stress Plastic

deformation
 Types of Deformation

 Elastic deformation: Particles partly get

modified in their shape.
 Deformation completely disappears after
withdrawal of the force.
 Examples: MCC, Acetyl salicylic acid.

 Plastic deformation: Particles completely

get modified in their shape.
 Above yield point deformation not
immediately reversible on removal of
applied force.
 Deformation beyond yield point leads to
plastic deformation.
 Cont…

 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.
 Fragmentation

Under high pressure the

01 particles get fragmented

Fragmentation leads the

smaller fragments to move into 02
voids

Fragmentation leads to
deformation of particles 03
Bonding

Intermolecular Liquid film Mechanical

theory surface theory theory
 Inter molecular theory

01 02 03 04

The molecules Compounds Under high

It occurs at pressure the van
at the surface containing OH
molecules at the der wals is
are connected groups created –H
surface created between
to the other bonding
particles particles
Liquid surface film theory

 Bonding to the presence of a thin liquid film which may be consequence

of fusion or solution at the surface of the particle induced by the energy of
compression. It may classified into two ways:

Hot
welding Cold
welding
 Cont…
 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.
 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.
Mechanical theory

It occurs in
irregularly
shaped particles

Mechanical It increases the

interlocking is contact of
not the major particles
mechanism

The total energy

is directly
proportional to
Deformation
Deformation of the solid body and Decompression

Toward a
limiting density
by plastic or
Non bonded elastic
solids get deformation of
consolidated tablet with in
the die
Increasing
pressure
Deformation
Cont…

 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.
 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:

To eject a tablet
involves the The final stage is
Second stage
distinctive peak marked by a
involves the force
force required to declining force of
required to push
initiate ejection ejection as the
the tablet up the
(breaking of die tablet emerges
die wall.
wall-tablet from the die.
adhesion)
 Force of Distribution

 For investigational purpose, the

fundamental based on tablet has been
carried out using single station presses.
 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
 In which ,
FA= Force applied to upper punch
FL= Force transmitted to lower punch
FD= Force at die wall
Cont…

 Because of 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
 Forces involved in Compression

 Frictional forces: These are interparticulate friction ( arise at particulate

contacts)and die wall friction- when material being pressed against the die
wall and moved down it- reduced by gildants (colloidal silica) and lubricants
(Mag. Stearate).
 Ejection forces: The necessary to eject a finished tablet is known as
Ejection force. Variation also occurs in ejection force when lubrication is
inadequate.
 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.
 The best lubricants are those with low shear strength but strong cohesive
tendencies in directions at right angles to the plan of shear.
Cont...

Die wall
lubrication
Shear strength of lubricants
Cont…

 Radial forces: As the compression force is increased after that repacking

of solid mass is completed, then material may be regarded as a single
body.
 In case of an unconfined solid body this would be accompanied by an
expansion in the horizontal direction of ∆D.
 The ratio of these two dimensional changes is known as the Poisson ratio λ
of the material, defined as,
 λ = ∆D/∆H
 Materials with larger Poisson ratio giving rise to (F R) Radial force
 The relationship between frictional force and radial force expressed by:
 FD=µw× FR
 µw is the coefficient of the die wall friction.
Cont…

 It is noted that radial force is reduced when materials of small Poisson

ratio are used.
 A common method of comparing degrees of lubrication has been to
measure the applied and transmitted axial force and determine the FL/FA.

 It is called as coefficient of lubrication or R value.

 R value below 0.8 probably indicates a poor lubrication.
 Equations for compression study

 Heckel equation: It is based on the assumption that densification of the bulk

powder under force follows first-order kinetics, 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
 Cont…

 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.

 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.
 Cont…

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.

Two regions of the heckle plots

are thought to represent the initial
repacking stage and subsequent
deformation process
 Tablet Compression Machine

Tablet Press
01 Hopper
04 Machine Cam
Tracks

Parts of tablet
compression Tablet press
machine
02 die-punch
05 Tablet Press
system Filling Station

Compression
03 Tablet press 06 Rollers and
tureet system Feeding
mechanism
Single punch tablet compression machine

 Stages of tablet compression:

 Die filling
 Tablet formation
 Tablet ejection
Multi station/Rotary compression machine
Properties of tablet influenced by Compression

Porosity

Hardness

Dissolution

Density
 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.
 Reference

 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.
 https://youtu.be/fSg86Zq_hQM