INTRODUCTION

 All along the history of pharmacy, oral route has been the most preferred way of drug
administration and oral solid dosage forms have been widely used mainly because of their
convenience of administration, ease of manufacturing, accurate dosing, and patient
compliance.
 Out of powders, granules, pellets, tablets, and capsules, tablets have been the dosage form of
first choice in the development of new drug entities and account for nearly 80% of all
pharmaceutical preparations.
 Thus, great interest has been focused on the design of tablet dosage forms with optimal
therapeutic properties.
 Tablets of various types and biopharmaceutical properties, from conventional immediate
release tablets to advance modified release systems exist, but their common denominator
is the way in which they are formed, that is, powder compaction.
 Over the years, literature has been confused about tableting terminology. Different terms such as
compressibility, compactibility, and tabletability, have been used to describe the same type of
relationship.
 Although these terms are used interchangeably these terms differ from each other on basis of three
variables: pressure, tensile strength, and porosity.
 Compressibility is defined as ability of a material to undergo a reduction in
volume as a result of an applied pressure.
 Compactibility is defined as ability of a material to produce tablets with
sufficient tensile strength under the effect of densification
 Tabletability is defined as capacity of a powdered material to be transformed
into a tablet of specified strength under the effect of compaction pressure.
Compaction
can be described as the process whereby a loose powder or granules is converted into a
coherent mass, usually by confining between die and punches.
The first step in the formation of a compact is the densification or reduction of the
porosity of the powder bed followed by the formation of inter particulate bonds that form a
stable and durable adhesive junction to produce a tough and rigid compact.
represents one of the most important unit operations in the pharmaceutical industry because
the physical and mechanical properties of the tablets are determined during this process.
Further, dosage form integrity and bioavailability are also related to the tablet compression
process.
 The development of compressed tablets is a complex process involving many variables and
engineering principles and a complete understanding of the physics of compaction.
Understanding the compaction process requires knowledge of the flow behavior of powder,
the densification mechanism, the formation of bonds, and the response of porous compact
during unloading and the ejection operation.
 Physical and bulk properties of drugs and excipients such as porosity, flow,
particle size, size distribution, crystal habit, polymorphism, and crystal
moisture affect the compression properties.
 Simple compression of bulk material into a robust tablet is also influenced
by process variables such as compression force, rate of force transfer,
particle deformation behavior and the adhesive forces between the
particles.
 The use of physical data to predict the tableting behavior of particles such
as compressibility and compactibility is limited and tablet formulation is
still based on empirical knowledge rather than on scientific theory.
 Thus, an improved theoretical understanding of the compaction process
will enable a more rational approach to the formulation of tablets.
 Compression
The ability of powder bed to cohere into or to form a compact or it is the ability of
powder material to be compressed into a tablet of specified tensile strength.
is a reduction in the bulk volume of material as a result of the displacement of gas.
in pharmaceutical tableting an appropriate volume of granules in a die cavity is
compressed between an upper and lower punch to consolidate the material into a
single solid dosage form and which is subsequently ejected from the die cavity as
an intact tablet.
 Consolidation:
is an increase in the mechanical strength of material resulting from particle-
particle interaction.
Compaction, as described earlier, is a mechanical process where the state of
material is changed from loose powder to coherent mass or compact of given
porosity. The compaction process is composed of the following stages:
(1) Compression and consolidation of the powder mass,
(2) Decompression of the compact, and
(3) Subsequent ejection of tablet from the die.
Before each or these simultaneous processes is discussed in more
detail, brief consideration is given to certain inherent properties of
all powdered solids, which contribute to the characteristics of
interest.
DERIVED PROPERTIES OF POWDERS OR GRANULES
FLOW PROPERTIES
 COMPRESSION PROPERTIES
This involves compressibility and compactability .
 Compressibility can be defined as the ability of a powder to decrease
in volume under pressure. Powders are normally compressed into
tablets using a pressure of about 5.0kg/cm2. The process is called
compaction & compression.

 Compactability can be defined as ability of powder to be compressed in to

a tablet of a certain strength or hardness.

 Thesetwo relate directly to the tableting performance. For proper

compression to occur the tablet should be plastic i.e., capable of permanent
deformation and it should also exhibit certain degree of brittleness.
 Deformation:
 When any solid body is subjected to opposing forces, there is a
finite change in its geometry, depending upon the nature of applied
load.
 The relative amount of deformation produced by such forces is a
dimensionless quantity called strain.
 Eg. If a solid rod is compresses by forces acting at each end to cause
a reduction in length of ΔH from an unloaded length of ΔH0 (Figure
b), then the compressive strain Z is given by:
 Z= ΔH/ ΔH0
Tensile strain: Tensile strain is defined as the deformation
or elongation of a solid body due to the application of a
tensile force or stress. In other words, tensile strain is
produced when a body increases in length as applied forces try
to "stretch" it.

Compressive strain: compressive strain is produced

when a body decreases in length when equal and opposite
forces try to compress.

Shear strain: Shear strain is the ratio of displacement to an

object's original dimensions due to stress.
 The ratio of the force F necessary to produce this strain to
the area A which it acts is called the stress σ:
σ = F/A
 When external mechanical forces are applied to a powder mass, there is normally a
reduction in its bulk volume as a result of one or more different effects.
 The onset of loading is usually accompanied by closer repacking of the powder
particles and in most cases, this is the main mechanism of initial volume reduction.
 In pharmaceutical tableting an appropriate volume of granules in a die cavity is
compressed b/w an upper & lower punch to consolidate the material in to a single
solid matrix, which is subsequently ejected from the die cavity as an intact tablet. The
subsequent events that occur in the process are:
1.Transitional repacking
2.Deformation at the point of contact
3.Fragmentation
4. Bonding
5. Deformation of the solid body.
6.Decompression.
7.Ejection.
 When the surfaces of two particles approach each other
closely enough, their free surface energies result in a strong
attractive force, a process known as cold welding.
 The nature of the bonds so formed are similar to those of the
molecular structure of the interior of the particles, but
because of the roughness of the particle surface, the actual
surface area involved may be small.
 This hypothesis is favored as a major reason for the
increasing mechanical strength of a bed of powder when
subjected to rising compressive forces.
 On the macroscale, most particles encountered in practice have an irregular
shape, so that there are many points of contact in a bed of powder which is
shown in figure.
 Any applied load to the bed must be transmitted through these particle
contacts; under appreciable forces, this transmission may result in generation of
considerable frictional heat.
 If this heat is not dissipated, the local rise in temp could be sufficient to cause
melting of the contact area of the particles, which would relieve the stress in that
particular region.
 In that case, the melt solidifies, giving rise to fusion bonding, which in turn
results in an increase in mechanical strength of the mass.
 In both cold and fusion welding, the process is influenced by several
factors including:
 The chemical nature of the materials
 The extent of the available surface
 The presence of surface contaminants
 The intersurface distances
 The type and degree of crystallinity in a particular material influences its
consolidative behavior under appreciable applied force.
 It was reported that substances possessing the cubic lattice arrangement
were tabletted more satisfactory than those with a rhombohedral lattice,
 The isotropic nature of the former group might be expected to contribute to
better tableting because no alignment of particulate lattice plane is required.
 In addition they provide three equal planes for stress relief at right angles to
each other.
 Lattice planes with greatest separation undergo plastic deformation more
readily, since such planes are more weakly bonded.
 The particles of most pharmaceutical powders consist of small crystallites
aggregated in a random manner so that their crystal planes are not aligned
with one another.
 Such an arrangement adds to the material’s resistance to plastic deformation.
 The more successful direct compression excipients that are
commercially available concerns that are commercially available
concerns this “material structure” aspect of tableting.
 Without exception, these products may be described as
microgranulations, sine they consist of masses of small crystallites
randomly embedded in a matrix of some glue-like (often
amorphous) material.
 Such a combination imparts the desired overall qualities, which
result in (1) strong tablets by providing a plastically deforming
component (the matrix) to relieve internal stresses and (2)
strongly bonding surfaces (the faces if the crystallites) to enhance
consolidation.
 The compressional process is affected by the extent of the
available surface, the presence of surface contaminants and the
intersurface distances.
 If large, clean surfaces are brought into intimate contact, then
bonding should occur.
 Brittle fracture and plastic deformation should generate clean
surfaces, which the compressional force ensures are kept in close
proximity.
 E.g. such lubricants as magnesium stearate form weak bons, so
that overlubrication, or even overmixing of lubricant into the
tableting mass, results in a continuous coating of the latter and
hence in some cases, weak tablets.
 The actual solubility of solids also depends somewhat on the applied
pressure, so that if a film of moisture is present on the solid surface, then the
high pressures at points of solid contact could force more material into
solution.
 Funicular
state: modest
Pendular state:
increase in
Low mechanical
strength
strength of
granules

Droplet formation:
Capillary Particles are held
State: maximum together but without
strength intragranular forces
so weaker
COMPRESSION AND CONSOLIDATION
UNDER HIGH LOADS

Die wall
tablet
punch

Thin layer is abrasion resistant but it –

 Retards air escape during compression.
 Retards the ingress of liquid media during dissolution.
 The process of tableting, roll compaction, and extrusion all involve
the application of massive compressive forces, which induce
considerable deformation in the solid particles.
 With many pharmaceutical solids and perhaps most tableting
mixtures, these forces are large enough to exceed the elastic limit
of the solid.
 Plastic deformation and/or brittle fractur then results in the
generation of new, clean surfaces, which being pressed against
one another, undergo cold welding.
 When the compaction force reaches its maximum, a bulk solid
structure of a certain overall strength will have been produced.
 At least two major component to the frictional
forces can be distinguished:
 Interparticulate friction:
 This arises at particle/particle contacts and can
be expressed in term of a coefficient of
interparticulate friction it is more significant at
low applied loads.
 Materials reduces this effect are referred to as
glidants.
 Ex: colloidal silica,talc,corn starch
 Die-wall friction
 The material being pressed against the die wall and
moved down it.
 The effect becomes dominant at high speed forces when
particle rearrangement has ceased and is particularly
important in tabletting operation.
 Most tablet contain small amount of an additive design to
reduce die wall friction.
 Such additives are called lubricants.
 Ex: magnesium stearate ,talc.
 Most investigation of the fundamentals of tabletting have
been carried out on single-station presses,or even on
isolated punch and die sets in conjuction with a hydraulic
press.
 The system represented diagrammatically in figure is typical
of such arrangements, with force being applied to the top of a
cylindric powder mass.
 The simple compaction system provides a convenient way to
examine the process in greater detail.
 FA=FL+FD
Where , FA=force applied to the upper
punch.
FL=force transmitted to the
lower punch.
FD=reaction at to the die wall
due to friction at the surface.
 Because of this inherent difference between the force applied at
the upper punch and that affecting material close to the lower
punch.
 The mean compaction force, FM

 A recent reports confirm that FM offers a practical friction-

independent measure of compaction load which is generally more
relevant than FA.
 A more appropriate geomatric mean force, FG ,might be:

 Use of these force parameters are probably more appropriate

than use of FA when determining relationships between
compressional force and such tablet properties as tablet
strength.
DEVELOPMENT OF RADIAL FORCE ( FR)

 As the compression force is increased and any repacking of the

tabletting mass is completed, the material may be regarded to some
extent as a single solid body.
 When compressive force is applied in one direction (vertical) results
in the decrease in height (ΔH) but in case of unconfined solid
body, this would be accompanied by an expansion in the horizontal
direction of ΔD. The ratio of these two dimensional changes is known
as poission ratio(λ) of the material, defined as:

λ = ΔD/ΔH
 The Poisson ratio is characteristic constant for each solid and may
influence tableting process. .
 Under the condition like compression the material is not free to
expand in horizontal plane bcoz its confined to die. Consequently, a
radial die-wall force FR develops perpendicular to die wall surface.
 Material with high Poisson ratio give higher FR value.
 As shown in figure, the material is not
free to expand in the horizontal plane
cause it is confined in the die.
 Consequently, a radial die-wall force FR
develops perpendicular to the die-wall
surface, materials with larger poisson
ratios giving rise to higher values of FR.
 Classical friction theory can be applied to obtain a relationship b/w axial
frictional force FD and radial force FR as;
FD =µw.FR
where, µw is coeff. of die wall friction.
 Frictional effect represented by, µw arises from shearing of
adhesions that occurs as the particles slide along the die wall. Its
magnitude is related to shear strength S and effective area of contact Ae b/w
two surfaces.
 Force transmission is maximum when FD is minimum which is achieved by
adequate lubrication of die wall(lower S) and maintaining min tablet
ht.(reducing Ae ).
 Degree of lubrication is compared to measure FA &FD and determine ratio of
FL/FA. This is called the coeff. of lubrication efficeincy or R value.
 It approaches1 for perfect lubrication, and in practice as high as
0.98 may be achieved.Values below0.8 indicate poor lubrication.
 Lubricants are added 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 the die
wall.
 Die-wall lubricant function by interposing a film of low shear
strength at the interface between the tableting mass and the die
wall.
 There is some chemical bonding between this boundary lubricant
and the surface of the die wall as well as the edge of the tablet.
 The best lubricants are those with low shear strength but strong
cohesive tendencies in directions at right angles to the plane of
shear.
 EJECTION FORCES
 Radial die forces & die wall friction also affect the ease with which the compressed
tablet can be removed from the die.
 The force necessary to eject a finished tablet follows a distintictive pattern of three
stages.
 The first stage involves distinctive peak force required to initiate ejection, by breaking
of tablet/die wall adhesions.
 A smaller force usually follows, that is required push the tablet up the die wall.
 The final stage is marked by a decline in force of ejection as the tablet emerges from
the die.
 Variation on this pattern are sometimes found when lubrication is
inadequate and/or “slip-stick” conditions occur b/w tablet an die
wall.
 Worn dies, which cause the bore to become barrel shaped gives rise abnormal
ejection force and may lead to failure of tablet structure.
 A direct connection exists b/w die wall frictional forces and force required to eject
tablet from die, FE.
 E.g. well lubricated system(large R value) have been shown to have smaller FE values.
 The end of the compressional process may be recognized as
being the point at which all air spaces have been eliminated. i.e.
Vb=Vt and therefore E=0.
 A small residual porosity is desirable, however, so there is
particular interest in the relationship between applied force FA
and remaining porosity E.
 Originally, it was suggested that decreasing porosity resulted from
a two-step process: (1) the filling of large spaces by
interparticulate slippage and (2) the filling of small voids by
deformation or fragmentation at higher loads.
 This process can be expressed mathematically:

 Where E0 is the initial porosity, E is the porosity at pressure P,

and K1, K2, K3 and K4 are constants.
A more complex sequence of events during compression
involves four stages as shown in figure.
 Stage i represents the initial repacking of the particles,
followed by elastic deformation (stage ii) until the elastic limit
is reached.
 Plastic deformation and/or brittle fracture then dominates
(stage iii) until all voids are virtually eliminated.
 At this point, the onset of stage iv, compression of the solid
crystal lattice occurs.
 In many tableting process, however once appreciable force has been applied,
the relationship between applied pressure (P) and some volume parameter
such as porosity (E) becomes linear over the range of pressure commonly used
in tableting.
 The foregoing equations have been criticized because some of the constants
apparently lack physical significance.
 Another equation, credited to Heckel, is free from this empiricism however.
 The Heckel equation is based upon analogous behavior to a first order
reaction, where the pores in the mass are the reactant, that is:

 Where Ky is a material dependent constant inversely proportional to its yield

strength S and Kr is related to the initial repacking stage and hence E0. E is
porosity
 The above relationship may be established by simply measuring the
applied compressional force F and the movements of the punches during
a compression cycle and translating this data into values of P (applied
pressure) and E (porosity).
 For a cylindric tablet, P is given by:

 Where D is the tablet diameter. Similarly, values of E can be calculated

for any stage from:

 Where w is the weight of the tableting mass, ρt is its true density, and H is
the thickness of the tablet at that point.
 The particular value of Heckel plots 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 degrees of porosity,
depending upon the initial packing in the die.
 This is in turn is influenced by the size distribution, shape, etc. of
the original particles.
 Heckel pots for such materials are
shown in figure type a, NaCl 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 Heckel plots for
different size fractions of the same
material that are typical of this
behaviour. Lactose is one such
material.
 Type a Heckel plots usually exhibit a higher final slope than type
b, which implies that the former materials have as expected, a
lower yield stress.
 Hard, brittle materials are, in general, more difficult to compress
than soft, yielding ones because fragmentation with subsequent
percolation of fragments is less efficient than void filling by plastic
deformation.
 In fact, as the porosity approaches zero, plastic deformation may
be the predominant mechanism for all materials.
 The two regions of the Heckel plot are thought to represent the
initial repacking stage and the subsequent deformation process,
the point of 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 heckel 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 plots can be influenced by the overall time of compression,
the degree of lubrication, and even the 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 a relatively
narrow optimum residual porosity range that provides adequate
mechanical strength, rapid water uptake and hence good
disintegration characteristics.
 Note also that the initial porosity can affect the course of the entire
compressional sequence, and that in general, slow force
application leads to a low porosity for a given applied load.
 APPLICATION OF HECKEL PLOT:
 Used to check lubricant efficacy.
 For interpretation of consolidation mechanisms.
 Duberg & nystom distinguish between plastic and elastic
deformation characteristics of a material.
 In operations such as tableting, the compressional
process is followed by decompression stage, as the
applied force is removed. This leads to a new set of
stresses within the tablet as result of elastic recovery,
which is augmented by the forces necessary to eject the
tablet from the die.
 Irrespective of the consolidation mechanism, the tablets
must be mechanically strong enough to accommodate
these stresses; otherwise structural failure will occur.
 If the stress relaxation process involves plastic flow, it may continue after
all compressional force has been removed and the residual radial pressure
will decay with time.
 The plastic flow can be interpreted in terms of a viscous and elastic
parameter. This interpretation leads to a relationship of the form:

 Where Ft is the force left in the viscoelastic region at a time t, and Fm is the
total magnitude of this force at time t=0. K is the viscoelastic slope and a
measure of the degree of plastic flow. Materials with higher K values
undergo more plastic flow; such materials often form strong tablets at
relatively low compaction forces.
 Alternatively, the changing thickness of the tableting mass due to the
compactional force, and subsequently due to elastic recovery during
uploading, can be used to obtain a measure of plastoelasticity у.

 Where H0, Hm and Hr are the thickness of the tablet mass at the onset of
loading, at the point of maximum applied force and on ejection from the
die, respectively.
 A linear relationship between у and log reciprocal of the tensile strength
of the tablets has been demonstrated.
 In general, values of у above 9 tend to produce tablets that are laminated
or capped.
 COMPACTION PROFILES
• Many attempts have been made to minimize the amount of applied force transmitted
radially to the die walls. All such investigations lead to characteristic hysteresis curves
called as compaction profiles. Radial pressure is developed due to the attempt of
material to expand horizontally. The plot of radial pressure against axial pressure leads
to hysteresis curve called as compaction profile.
• The radial die-wall force arises as a result of the tableting mass attempting to expand in
the horizontal plane in response to the vertical compression.
• The ratio of these two dimensional changes, the Poisson ratio, is an important material
dependent property affecting the compressional process.
• When the elastic limit of the material is high, elastic deformation may make the major
contribution, and on removal of the applied load, the extent of the elastic relaxation
depends on the value of the material’s modules of elasticity (young’s modulus).
• Lower the modulus higher will be the elastic relaxation. Then there will be the danger of
structural failure. Higher the modulus value results in low decompression hence lesser
risk of structural failure.
 The area of hysteresis loop (OABC’) indicates the extent of
departure from ideal elastic behavior, since for a perfectly
elastic body, line BC’ would coincide with AB.
 In many tableting operations, the applied force exceeds the
elastic limit (point B) and brittle fracture and/or plastic
deformation is then a major mechanism.
 For example, if the material readily undergoes plastic
deformation with a constant yield stress as the material is
sheared, then the region B to C should obey the equation:

 Where S is the yield strength of the material.

 The mechanics of tablets is very complex and a great deal of scientific effort is
required to analyze compaction behavior of tablet. Compaction profiles, obtained
from instrumented punches and dies, can be fitted to mathematical equations to
elucidate the compaction behavior.
 Tablet machines, roll compactors, extruders and similar types of
equipment require a high input of mechanical work.
 The work involved in various phases of a tablet or granule
compaction operation includes
 That necessary to overcome friction between particles
 That necessary to overcome friction between particles and machine
parts
 That required to include elastic and/or plastic deformation of the
material
 That required to cause brittle fracture within the material.
 That associated with the mechanical operation of various machine parts.
 Compaction data obtained from tableting machine are 3 types:
 A. force time profile
 B. force displacement profile
 C. die wall force profile
 Compression force-time profile are used to characterize the
compression behaviour of the active ingredients and
excipients:
on a rotary tablet press,the force time curves are
segmented in to three phases:
1.Compression phase:
compression is the process in which maximum force is
applied on powder bed in order to reduce its volume.
 When compression force reaches a maximum value,this
maximum force is maintained for a prolonged period of time
before decompression.
 The time period between the compression phase and
decompression phase.
 Removal of applied force on powder bed,both punches
moving away from upper and lower surface.
  (a) Compression force-time profiles

 Compression force-time profiles are used to characterize compression behavior of tablet

components with respect to their plastic and elastic deformation. A usual force-time curve as
described in figure is segmented into three phases:

Figure: A typical compression force – time curve

Compression phase: when there is horizontal and vertical punch movement.
Dwell phase: when there is only horizontal punch movement as plane punch head area is under compression roller.
Decompression phase: when both punches move away from tablet surface.
 The force-time profile gives information about these phases as well as about various
characteristic parameters of the compression cycle.
 In the force-time profile, the time to reach maximum force is called as
consolidation time, the time at which maximum displacement occurs is called as
dwell time, and the time for compression and decompression is called as contact
time.
 Compression area: The area under the curve A1 called as compression area
represents compression phase. Compression area is related to density of material
and for low density excipients such as micro crystalline cellulose, A1 is large and
for high density excipients such as dicalcium phosphate, A1 is small.
 Dwell-time coefficient: The area ratio of A6 by A5, called as dwell-time coefficient
can be used to measure the plasticity of a substance. The sharp curve and decrease
in force over dwell time is indicative of plastic materials whereas plateau is
observed for brittle substances like dicalcium phosphate and crystalline lactose.
 Peak offset time: Peak offset time is the difference between the time of maximum
pressure and the middle of the dwell time. The duration of peak offset time depends
on the ability of the compacted powder to relieve stress and thus is indicative of
mechanisms of particle deformation during consolidation. Short values are
characteristic of materials that consolidate mainly by brittle fracture whereas longer
values indicate plastic flow.
 Decompression area: The area under the decompression curve, A4, is a measure of
fast elastic expansion.
 These parameters along with total area under the force-time curve are used for phase
specific allocation of the occurrence of plastic flow.
 (b) Force-Displacement Profile

 A common method for assessment of the compaction behavior of materials is the use of
compression force versus punch displacement profiles, from which the work involved during
tablet compaction can be calculated.
 A typical Force-displacement profiles is shown in figure:

Figure: A typical force – displacement curve

 Assesment of the compaction behaviour of
materials is done by force-displacement profile:
 force-displacement
profile can be used to
determine the behavior of plastic and elastic
materials.
 Stress relaxation is observed to be less in case of
plastic deformation;where as materials that
undergoes elastic deformation tend to relax to a
greater extent during and after decompression.
 This function can be used to predict the compaction
behaviour of pharmaceutical material.
 During tableting friction arises between the material and
the die wall and also between particles (interparticulate or
internal friction).
 Internal friction is significant only during particle slippage
and rearrangement at low applied pressure.
 The coefficients of friction related to tableting process are:
1)Static friction
2)Dynamic friction
 Static friction: force require to initiate sliding
 Dynamic friction: force to maintain sliding between two
surfaces
 The relationship between compaction pressure and volume reduction
or density increase has been widely studied and several equations
have been proposed to fit curves based on pressure and volume
fraction.
 These equations provide an understanding of the basic mechanisms of
the compaction process and also the magnitude of the resulting
compact strength as well as characterizing the overall compaction
process.
 PROPERTIES OF TABLET INFLUENCED BY
COMPRESSION

1.Density and porosity:

 The apparent density of a tablet is exponentially related to applied
pressure (or compressional force) until the limiting density of the
material is achieved.
 As compressional force increases the density of tablet also
increases as a result of decrease in bulk volume.
 As the porosity and apparent density are inversely proportional, the
plot of porosity against log of compression force gives linear plot
with a negative slope.

2. Hardness and tensile strength

Specific surface area:
 Specific surface area initially increases to a maximal value as
the force increases, indicating the formation of new surface
due to fragmentation of granules.
 Further increase in force produce a progressive decrease in
surface area due to bonding of particles.
Disintegration:
 Usually as the applied pressure used to prepare a tablet is
increased, the disintegration time increases (lactose/aspirin
alone).
 Frequently, there is exponential relationship b/w disintegration
time and pressure (aspirin-lactose).
 In some formulation there is minimum value when
app.pressure is plotted against log of disintegration time (with
10% and 15% starch in sulfadiazine tablets)
 For tablets compressed at low pressure, there is a large void,
and the contact of starch grains in the interparticular space is
discontinuous. Thus there is a lag time before the starch
grains, which are swelling due to imbibitions of water, contact
and exert a force on surrounding tablet structure.
 For tablets compressed at certain applied pressure, the
contact of starch grains is continuous with the tablet structure,
and the swelling of starch immediately exerts pressure,
causing the most rapid disintegration.
 For tablets compressed at pressures greater than that
producing minm disintegrtaion time, the porosity is such that
more time is required for the penetration of water into the
tablet, hence increase in disintegration time.
 Dissolution: The effect of applied pressure on dissolution rate
may be considered from viewpoint of disintegrating and non-
disintegrating tablets.
 Shah & Parrot showed that, the dissolution rate is independent
of applied pressure from 53 to 2170 kg/cm2 for non-
disintegrating spheres of aspirin, benzoic acid, salicycic acid,
an equimolar mix.of aspirin & salicylic acid, aspirin & caffeine.
 Mitchell and Savill found dissolution rate of aspirin disk to be
independent of pressure over 2000 -13000 kg/cm2 and
independent of particle size of granules used to prepare disks.
Similar observation was found for benzoic acid disks.
 The effect of applied pressure on dissolutionof disintegrating tablet
is difficult to predict.
 If fragmentation of granules occur during compression, the
dissolution is faster as the applied pressure is ↑ed , bcoz of ↑se in
specific surface area.
 If bonding of particle is predominate phenomena in compression, ↑se
in applied pressure, ↓se dissolution.
The four most common dissolution-pressure relations are:
1. The dissolution is more rapid as pressure is increased.
2. The dissolution is slowed as pressure is increased.
3. The dissolution is faster, to a maxm, as force is increased, and
further increase in force slows dissolution.
4. The dissolution is slowed to a minm as pressure is ↑ed, and then
further an increase in pressure speeds dissolution.
 t50% (min)
Pressure
Starch paste Methylcellulose Gelatin solution
(MN/cm2)
solution

200 54.0 0.5 10.0

400 42.0 0.8 4.5
600 35.0 1.1 3.0
800 10.0 1.2 4.6
1000 7.0 1.4 4.9
2000 3.3 1.8 6.5

Table: Effect of compressional force on dissolution of

Sulfadimide tablets prepared with various garnulating agents
 FACTORS AFFECTING STRENGTH OF TABLETS
 The ability of a tablet to withstand mechanical handling and transport
has been evaluated by various types of tests (abrasion, bending,
idention, hardness, diametral crushing).
 The strength of a tablet may be expressed as a tensile strength
(breaking stress of a solid unit in kg/cm2).
 Factors affecting tablet strength are
I. Particle size
II. Moisture content
III. Lubricants
IV. Applied pressure
1.PARTICLE SIZE:-
 A decrease in particle size resulted in the increase in the tablet
strength.
 Very large particle often exists as agglomerates of small crystal on
compression such agglomerates , being more friable than the
crystal, breakdown in smaller units. The strength of the tablets
prepared from such aggregates is higher.
 With very fine particle , such as those produced by a fluid energy mill
, the powder are very cohesive even in the uncompressed state. On
compaction strong compact of tablet can be formed .
 At a given pressure the use of a very small particle increases the
chances of grapping & the volume of air entrapped also increases.
 General equation formed for the effect of particle size is
Fc = Ka/√d
 Where, K= constant
a= material constant lies between (0.2 to 0.47)
Fc= hardness of the impact
d= diameter of the granule
2. MOISTURE CONTENT:-
 In the preparation of the pharmaceutical tablet , it is generally
accept that a small proportion of the moisture is present and
in some cases this is required to form a coherent tablets.
 Wet granulation of the powder material with hydrophilic
additive was shown to yield tablet whose mechanical strength
is dependant on the optimum content above or below with
the tablets strength was reduced
 With the optimum moisture content there is :
Die wall lubrication
Inter-particulate lubrication
Hydro-dynamic resistance to consolidation
Expression of intestinal liquid to the die wall
 At low moisture content: ↑ed die wall friction due to ↑ed
stress ratio, poor tablet hardness.
 At high moisture content: moisture acts as lubricant , hence
↓ed die wall friction
 At further ↑se in moisture content: Further ↑se in
moisture, ↓se in compact strength due to ↓se in
interparticulate bond.

 Hence a granulation should contain an optimum moisture

content.
 It has been reported that the optimum moisture content for
starch granulation of lactose is approximately 12% and that
of phenacetin is 3%.
3. LUBRICANTS
 The chief purpose of a lubricant is to minimize friction at die
wall, although they often enhances flow of granules by
decreasing inter-particular friction.
 Lubrication mechanism: The polar portion of lubricant adhere
to oxide-metal surface and interpose a film of low shear
strength at interface b/w die wall and tablet.
 A lubricant reduces ejection force.
 Although a lubricant is added to facilitate its process of
tableting, its presence affects several properties of tablet.
 The effect of lubricant on mechanical strength of tablet
depends on mechanism of bonding.
 The strongest bonds are formed b/w clean, new surface; and
for material that undergo plastic and/or elastic deformation. In
such cases lubricants acts as a physical barrier b/w new
surface. Hence strength decreases.
 Eg. A tablet of MCC, whose bonding occurs primarily through
plastic deformation and flow, is mechanically weakened by
lubricant. The addition of Mag.stearate markedly decrease
axial and tensile strength in MCC as well as Lactose tablet.
 For materials that are brittle and fragment, new, clean
surfaces are formed and readily bond during compression,
and the lubricant has little detrimental effect on strength of
tablets.
 Dibasic calcium phosphate dihydrate is consolidated by brittle
fraction, and its axial and radial tensile strength are not
significantly changed by addition of as much as 3% of
mag.stearate.
 Stearic acid, hydrogenated veg.oil, talc and PEG 4000 may be
used in concn as great as 8% for brittle material with only a
slight to moderate change in tensile strength.
4. EFFECT OF APPLIED PRESSURE

 At higher forces due to fragmentation new surfaces are

formed causing an increase in surface area, hence more area
is available for bond formation, hence more will be the
hardness of the compact.
 There is a linear relationship b/w tablet hardness and the
logarthim of applied pressure except at high pressures.
 According to Balshin eqn.
Fc = Fc0 V r-m
Where,
Fc0 = strength of the tablet when Vr =1 (i.e. completely
consolidated)
m = is a constant for particular system
 Vr is the relative volume defined as Vr = 1/1-ε
Where ε is the porosity of the compact
 And, shotton and Ganderton gave a general equation for
the effect of applied pressure on the strength of the
compact.
Log P = nFc + C
Where, P= applied pressure
Fc= strength of the compact
C= constant
When we extraplot the plot of logP vs Fc ,the intercept
gives the value of C, which probably represents the
minimum pressure required for the formation of tablet.
MINIMIZING CAPPING
AND LAMINATION.
 use of flat punch.
 use of tungsten carbide insert.
 proper set up of press.
 addition .
 use of binders.

04/21/16