TABLET FORMATION PROCESS

 The mechanical criteria for a successful tablet formulation are good flowability for
powders and adequate strength without fracture for compacts.
 The quality of a compressed tablet is determined by powder characteristics and
compression behaviour.
 Powder characteristics depend upon flow properties that are primarily affected by particle
size and shape. Additionally, high interparticle friction can have a detrimental effect on
powder characteristics due to bridging and non-uniform flow.
 A non-uniform particle size distribution may also lead to material segregation resulting in
uniformity problems.
 The tableting characteristics of powders depend on the viscoelastic properties of the
material.
 The process of compaction has been defined as “the compression and consolidation of a
two-phase system due to an applied load.” The quality of the compact depends on the
compression and consolidation of the powder mass, decompression of the compact,
ejection from the die, and subsequent scrape-off from the lower punch.
 A schematic representation of the compression process is shown in Fig. Tablet quality is
affected by both the magnitude and the rate of application of the compression force since
viscoelastic properties are time dependent.

Process of Compression
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The various events that occur in the process of compression are,

A. Transitional repacking
B. Deformation at the points of contact
C. Fragmentation and/or deformation
D. Bonding
E. Deformation of the solid body
F. Decompression and
G. Ejection
A. TRANSITIONAL REPACKING OR PARTICLE REARRANGEMENT:
 The particle size distribution of the granules and the shape of the granules determine the
initial packing (bulk density) as the granulation is delivered in to the die cavity.
 The granules flow with respect to each other, with the finer particles entering the void
between the larger particles, and the bulk density of the granulation is increased.
 Spherical particles undergo less particle rearrangement than irregular particles as the
spherical particles tend to assume a close packing arrangement initially.
 To achieve a fast flow rate required for high speed presses the granulation is generally
processed to produce spherical or oval particles.
 Particle rearrangement and the energy expended in rearrangement are minor
considerations in the total process of compression.
B. DEFORMATION AT THE POINTS OF CONTACT:
 When a stress is applied to a material, deformation (change of form) occurs.
 If the deformation disappears completely (returns to the original shape) upon release of
the stress, it is elastic deformation.
 A deformation that does not completely recover after release of the stress is known as a
plastic deformation.
 aThe force required to initiate a plastic deformation is known as the yield stress.

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  When the particles of granulation are so closely packed that no further filling of the void
can occur, a further increase of compressional force causes deformation at the points of
contact.
 Both plastic and elastic deformation may occur although one type predominates for a
given material.
 Deformation increases the area of true contact and the formation of potential bonding
areas.
C. FRAGMENTATION AND/OR DEFORMATION:
 At higher pressure, fracture occurs when the stresses within the particles become great
enough to propagate cracks.
 Fragmentation furthers densification, with the infiltration of the smaller fragments into
the void space.
 Fragmentation increases the number of particles and forms new, clean surfaces that are
potential bonding areas.
 In some materials fragmentation does not occur because the stresses are relieved by
plastic deformation.
D. BONDING:
 Several mechanisms of bonding in the compression process have been conceived, but
they have not been substantiated by experimentation and have not been useful in the
prediction of the compressional property of material.
 The three theories which describe the bonding process are,
i. The mechanical theory,
ii. The intermolecular theory and
iii. The liquid surface theory.
i. The Mechanical theory:
 It proposes that under pressure the individual particles undergo elastic, plastic or brittle
deformation and that the edges of the particles intermesh, forming a mechanical bond.

3
  If only the mechanical bond exists, the total energy of compression is equal to the sum of
the energy of deformation, heat and energy adsorbed for each constituent.
 Mechanical interlocking is not a major mechanism of bonding in pharmaceutical tablets.
ii. The Intermolecular theory:
 The molecules (or ions) at the surface of a solid have unsatisfied intermolecular forces
(surface free energy) which interact with other particles in true contact.
 According to the intermolecular theory, under pressure the molecule at the points of true
contact between new, clean surfaces of the granules are close enough so that Van der
Waals forces interact to consolidate the particles.
iii. The liquid surface theory:
 The liquid-surface film theory attributes bonding to the presence of a thin liquid film,
which may be the consequence of fusion or solution, at the surface of the particle induced
by the energy of compression.
 During compression an applied force is exerted on the granules; however, locally the
force is applied to a small area of true contact so that a very high pressure exist at the true
contact surface.
 The local effect of a high pressure on the melting point and the solubility of the material
is essential for bonding.
 The relation of pressure and melting point is expressed by the Clapeyron equation,

dT T(V1-Vs) = dP ΔΗ

Where,

dT/dP - Change in melting point with change in pressure,

T - Absolute temperature,

ΔΗ – Molar latent heat of fusion,

V & V - Molar volume of the liquid melt and the solid respectively.

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  If the pressure at the point of true contact is exerted only on the solid and the liquid
phase is subjected to a constant atmospheric pressure, the relationship simplifies to,

dT dPs VT ΔΗ

Where,

dT/dP is positive, regardless of the expansion or contraction of the solid, the

pressure acting locally at the point of true contact lowers the melting point.

E. DEFORMATION OF THE SOLID BODY:

 As the applied pressure is increased, the bonded solid is consolidated towards a limiting
density by plastic and/or elastic deformation of the tablet within the die.
 The effect of applied pressure on the apparent density of tablets of sulfathiazole is given
below,

F. DECOMPRESSION:
 The success or the failure to produce an intact tablet depends on the stresses induced by
elastic rebound and the association deformation process during decompression and
ejection.
 Often, if capping or lamination of the eject tablet has occurred, the individual pieces are
dense, hard and strongly bonds indicating that sufficient areas of true contact existed
during compression.
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 As the upper punch withdraw from the die cavity, tablet is confined in the die cavity by a
radial pressure.
 Ideally, if only elastic deformation occurred, with the sudden removal of the axial
pressure the granule would return to their original form breaking any bonds that may
have formed under pressure.
 Also, the die wall pressure will be zero as the elastic material recovered axially and
contracted radially.
 As the movement of tablet is restricted by the residual die wall pressure and friction, the
stress from axial elastic recovery and radial contraction cause capping.
 Capping is due to uniaxial relaxation in the die cavity at the point where the upper punch
pressure is release.
 If decompression occurs simultaneously in all directions capping is reduced.
 Stress relaxation of plastic deformation is time dependent.
 Material having slow rates of stress relaxation crack in the die upon decompression.
 In fig, the ratio of pressure at time to the maximum pressure is plotted against the
logarithm of the time.
 The change of the initial slope suggests some prominent mechanism of bonding soon
becomes negligible.
 The initial slope reflects the ability of the material to relieve stress during decompression.
 The rate of stress relieve is slow for acetaminophen so cracking occurs while the tablet is
within the die.
 With microcrystalline cellulose the rate of stress relieve is rapid and intact tablets result.
 If stress relaxation is slow and cracking is a problem, a slower operation speed provides
more time for stress relaxation.
 A tablet press that provides pre-compression allows some stress relaxation before the
final compression.
 To optimized the stress relaxation, before final compression the pre-compression pressure
should be approached the maximum pressure.

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 G. EJECTION:
 As lower punch rises and pushes the tablet upward there is continue residual die wall
pressure and energy must be expanded due to die wall friction.
 As the tablet is removed from the die, the lateral pressure is relieved, and tablet under
goes elastic recovery with increase in volume of that portion of the tablet removed from
the die.
 During the ejection that portion of the tablet within a die is under strain, and if this strain
is exceed the share strength of the tablet, the tablet caps adjacent to the region in which
the strain had just been removed.

COMPRESSION

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 of the following 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.

As the load increases, however, rearrangement becomes more difficult, and further compression
involves some type of particle deformation as mentioned here under:

Elastic Deformation
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If on removal of the load, the deformation is to a large extent spontaneously reversible, i.e. if it
behaves like rubber, then the deformation is said to be elastic. All solids undergo some elastic
deformation when subjected to external forces. With several pharmaceutical materials, such as
acetylsalicyclic acid and microcrystalline cellulose, elastic deformation becomes the dominant
mechanism of compression within the range of maximum forces normally encountered in
practice.

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 predominates in materials in which the shear strength is less
than the tensile or breaking strength.

Brittle Fracture

Conversely, 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 most 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.

Microsquashing

Irrespective of the behavior of large particles of the material, small particles may deform
plastically, a process known as microsquashing, and the proportion of fine powder in a sample
may therefore be significant. Asperities that are sheared off larger, highly irregular particles
could also behave in this way, thus, particle shape is another important factor. The above
account describes all of the possible mechanisms that can contribute to a reduction in the bulk
volume of a bed of powder, when subjected to external mechanical forces. The chemicophysical
characteristics of the material being studied determine the contribution each effect makes as the
8
compressional load is increased. All of the deformation effects may be accompanied by the
breaking and formation of new bonds between the particles, which gives rise to consolidation as
the new surfaces are pressed together.

CONSOLIDATION

Consolidation is an increase in mechanical strength of material from particle- particle

interaction.

 Mechanism:
i. Cold welding
ii. Fusion welding
iii. Recrystallization
I. Cold welding:
 When the surface of 2 particles approaches each other closely enough <50 nm, their
energies result in a strong attractive force.
 This mechanism is cold welding.

II. Fusion welding:

 When load is applied, frictional heat can be generated.

 If this heat is not dissipated, the local rise in temperature 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.

III. Recrystallization:

 The actual solubility of solid also depends somewhat on the applied pressure, so that if a
film of moisture is present on the solid surface, then the high pressure at the point solid
contact could force more material into solution.
 This dissolved solid would crystallize on relief of the applied stress to form a solid bridge
whose strength would partly depend on the rate of recrystallization.

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  In general, slow rate should produce a more prefect crystal structure with consequent
higher strength.
 Factors Affecting Consolidation process:
I. Chemical nature of material
II. Extent of available surface
III. Presence of surface contaminants
IV. Inter-surface distance

i. Chemical nature of material:

 The type and degree of crystallinity in a particular material influences its consolidative
behaviour under appreciable applied force.
 Substances possessing the cubic lattice arrangement were tableted more satisfactorily
than those with a rhombohedral lattice.

Ii. Extent of available surface:

 The compressional process is affected by the extent of available surface.

 When a powder mass is subjected to increasing compressional force, there is initial
particle fracture, which gives rise to increased surface area (O to A).
 At the point A, particles re-bonding becomes dominant factor, and from then on surface
area decreases unless tablet lamination begins.

Iii. Presence of surface contaminants:

 The compressional process is affected by the extent of presence of surface contaminant.

 For example, lubricants such as magnesium stearate form weak bond, so that over
lubrication or even over-mixing of lubricant into the tableting mass, results in a
continuous coating of the latter, and hence in some cases weak tablets are formed.

Iv. Inter-surface distance:

10
  At the low level of external forces, molecular and electrostatic forces are source of
attractive tendencies between individual particles.
 Van Der Waal’s forces however may exert a significant effect at distance upto 100nm, so
that once an agglomerate of particles has been formed, they may serve to prevents its
breakdown.
 Role of Moisture

Introduction

Moisture, even in trace amounts, plays a significant role in the behavior of powders and
granules during tablet compression. It affects the mechanical properties of the material, the
transmission of compressional forces, and the final tablet characteristics. The provided data
highlights how moisture influences consolidation and tablet quality.

Effects of Moisture in Consolidation

I. Force Transmission During Compression

 Moisture content, even at very low levels (e.g., 0.02%), can dramatically alter the way
compressional forces are transmitted through the powder bed.
 For example:
o At 0.02% moisture, the proportion of the applied force transmitted to the lower pun is
affected.
o At 0.55% moisture, the behavior of the material can reverse compared to completely
dry material. This indicates that moisture changes the internal friction and plasticity of
the powder bed.
II. Void Filling and Expulsion of Moisture
 When the moisture content is just enough to fill the remaining voids in the powder bed,
further compression can lead to the expulsion of this moisture to the tablet surface.
 This expelled moisture can have two effects:
o Lubrication: It may act as a lubricant at the die wall, reducing friction and improving
tablet ejection.
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 o Sticking: It can also cause material to stick to the punch faces, leading to
manufacturing issues like sticking or picking.
III. Impact on Tablet Strength
 Moisture content affects the crushing strength (hardness) of tablets. For example:
 In hydrates, thermal dehydration (removal of water) can alter the crushing strength of
tablets.
 The temperature at which dehydration occurs also influences tablet strength. Higher
dehydration temperatures can lead to a more porous crystal structure, reducing tablet
strength.
 Scanning electron microscopy (SEM) studies confirm that dehydration changes the
texture of crystals, making the mass more porous and less cohesive.

IV. Role in Granulation Processes

 Moisture is critical in wet granulation, where aqueous solutions are used to form
granules.
 During granulation, moisture helps in:
o Particle Bonding: It acts as a binding agent, promoting adhesion between
particles.
o Plasticity: It increases the plasticity of the material, making it easier to deform
and bond under pressure.
 After granulation, the residual moisture content must be carefully controlled to ensure
optimal compressibility and tablet quality.

Mechanisms of Moisture in Consolidation

A. Plasticization

 Moisture acts as a plasticizer, reducing the glass transition temperature (Tg) of polymers
and making materials more deformable under pressure.
 This enhances plastic deformation, which is essential for strong interparticulate bonding.

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B. Capillary Forces

 Moisture creates capillary forces between particles, promoting adhesion and cohesion
during the initial stages of consolidation.

C. Solid Bridge Formation

 Moisture can dissolve small amounts of material at particle surfaces, which then
recrystallizes upon drying, forming solid bridges between particles. This is particularly
important for materials like lactose or sucrose.

Practical Implications in Tablet Manufacturing

A. Optimal Moisture Content

 A small amount of moisture (typically below 1%) is often beneficial for tablet
compression. It improves plasticity, bonding, and tablet hardness.
 However, excessive moisture can lead to:
o Sticking: Material sticking to punch faces.
o Capping: Tablets splitting into layers due to excessive elasticity.
o Poor Hardness: Over-plasticization can reduce interparticulate bonding.

B. Environmental Control

 The relative humidity (RH) of the manufacturing environment must be controlled to

prevent moisture uptake or loss by the powder or granules.
 Hygroscopic materials (e.g., microcrystalline cellulose) are particularly sensitive to
environmental moisture.

C. Drying Process

 After wet granulation, the drying process must be carefully optimized to achieve the
desired residual moisture content.
 Over-drying can remove too much moisture, leading to poor compressibility, while
insufficient drying can result in excessive moisture, causing sticking or picking.
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Examples

 Hydrates: The crushing strength of tablets made from hydrates depends on the
temperature of dehydration. Higher temperatures lead to a more porous structure and
weaker tablets.
 Low Moisture Levels: Even 0.02% moisture can significantly affect force transmission
during compression, highlighting the sensitivity of powders to moisture

Conclusion

Moisture plays a critical role in the consolidation process during tablet compression. It affects
force transmission, plasticity, bonding, and tablet strength. However, the amount of moisture
must be carefully controlled to avoid issues like sticking, capping, or poor tablet hardness. The
provided data underscores the importance of optimizing moisture content for successful tablet
manufacturing.

 Compression and Consolidation under High Loads

 The processes of tabletting, 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 tabletting mixtures, these forces are
large enough to exceed the elastic limit of the solid (or at least that of one component of the
mixture).
 Plastic deformation and/or brittle fracture 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. Irrespective of the bonding mechanism, this structure must
be strong enough to withstand the new stresses induced during release of the applied load
and those generated by ejection from the die (in the case of tabletting).
 Ideally, relief of these stresses by elastic recovery is preferred, since at this stage, plastic
deformation—and even worse, brittle fracture—may result in small failure planes, if not
complete lamination, since any new surfaces tend to separate rather than consolidate.

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 During normal tabletting operations, consolidation is accentuated in those regions adjacent
to the die wall, owing to the intense shear to which material is subjected, as it is compressed
axially and is pushed along the wall surface.
 This consolidation results in a “skin” of material that is denser over the lateral tablet surface
than in the rest of the tablet mass. This skin is in some cases visible to the naked eye.
 Although this thin layer of material may contribute to abrasion resistance, it may retard the
escape of air during compression and the ingress of liquid during dissolution, both
undesirable features. For these reasons, smaller tablet height-to-diameter ratios are preferred.
 This situation is advantageous from additional standpoints, which are now to be considered.
 The resistance to differential movement of particles caused by their inherent cohesiveness
results in the applied force not being transmitted uniformly throughout the entire mass.
 More specifically, in the case of a single station press, the force exerted by the upper punch
diminishes exponentially at increasing depths below it. Thus, the relationship between upper
punch force FA and lower punch force FL* may be expressed in the form:
FL = FA · e−KH/D
o where, K is an experimentally determined material-dependent constant that includes a
term for the average die-wall frictional component.
 The values H and D are the height and diameter of the tablet, respectively. The discrepancy
between the two punch forces should be minimized in pharmaceutical tabletting operations,
so that there is no significant difference in the amount of compression and consolidation
between one region of the tablet and another.
 Reduction of die-wall friction effects by having smaller tablet height-to-diameter ratios and
by adding a lubricant is therefore common practice.
 Because of their important role in the progress of the compressional sequence, frictional
effects warrant further discussion.
 Effects of Friction
At least two major components to the frictional forces can be distinguished.

15
 I. Interparticulate friction: This arises at particle/particle contacts and can be expressed in
terms of a coefficient of interparticulate friction μ1; it is more significant at low applied
loads. Materials that reduce this effect are referred to as glidants. Colloidal silica is a
common example.
II. Die-wall friction: This results from material being pressed against the die wall and
moved down it; it is expressed as μw, the coefficient of die-wall friction. This effect
becomes dominant at high applied forces when particle rearrangement has ceased and is
particularly important in tabletting operations. Most tablets contain a small amount of an
additive designed to reduce die-wall friction; such additives are called lubricants.
Magnesium stearate is a common choice.
 Force Distribution
 Most investigations of the fundamentals of tabletting have been carried out on single station
presses (sometimes called eccentric presses), or even on isolated punch and die sets in
conjunction with a hydraulic press.
 The system represented diagrammatically in Fig is typical of such arrangements, with force
being applied to the top of a cylindric powder mass.
 This simple compaction system provides a convenient way to examine the process in greater
detail. More specifically, the following basic relationships apply.
 Since there must be an axial (vertical) balance of forces:
FA = FL + FD
o where, FA is the force applied to the upper punch, FL is that proportion of it
transmitted to the lower punch, and FD is a reaction at the die-wall due to friction at
this surface.
 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:
F A+ FL
FM=
2

16
 A recent report confirms that 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) ½
 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
 As the compressional 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.
 Then, as with all other solids, compressive force applied in one direction (e.g. vertical)
results in a decrease ΔH in the height. In the case of an 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 the Poisson ratio (λ) of the material,
defined as: The Poisson ratio is a characteristic constant for each solid and may influence the
tabletting process in the following way. Under the conditions illustrated in Fig, the material
is not free to expand in the horizontal plane because 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.

Diagram of a cross-section of a typical simple punch and die assembly used for compaction
studies
17
 Classic friction theory can then be applied to deduce that the axial frictional force FD is
related to FR by the expression:
FD = μw × FR
o where, μw is the coefficient of die-wall friction. Note that FR is reduced when
materials of small Poisson ratios are used, and that in such cases, axial force
transmission is optimum.
 The frictional effect represented by μw arises from the shearing of adhesions that occurs as
the particles slide along the die wall.
 It follows that its magnitude is related to the shear strength S of the particles (or the diewall-
particle adhesions if these are weaker) and the total effective area of contact Ae between the
two surfaces.
 Therefore, force transmission is also realized when FD values are reduced to a minimum,
which is achieved by ensuring adequate lubrication at the die wall (lower S) and maintaining
a minimum tablet height (reducing Ae).
 A common method of comparing degrees of lubrication has been to measure the applied and
transmitted axial forces and determine the ratio FL/FA.
 This is called the coefficient of lubricant efficiency, or R value. The ratio approaches unity
for perfect lubrication (no wall friction), and in practice, values as high as 0.98 may be
realized.
 Values below 0.8 probably indicate a poorly lubricated system. Values of R should be
considered as relating only to the specific system from which they were obtained, because
they are affected by other variables, such as compressional force and tablet H/D ratio.
 Die-wall Lubrication
 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 tabletting mass and the die wall, as illustrated in Fig.

18
 Preferably, there is some chemical bonding between this “boundary” lubricant and the
surface of the die wall as well as at 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. Table gives the shear strength of some
commonly used lubricants as measured by a punch penetration test.
 By utilizing materials with low shear strength as lubricants, shear failure occurs in the
lubricant layers and not at the compressed powder or resultant wall interfaces.

Diagram illustrates the preferred characteristics of die wall lubricants

The shear strength of some lubricant
Material Shear strength (MPa) Material Shear strength (MPa)
Stearic acid 1.32 Talc 6.20
Calcium stearate 1.47 Boric acid 7.16
Magnesium stearate 1.96 Graphite 7.35

 Ejection Forces
 Radial die-wall forces and 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 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, namely that 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.

19
 Variations on this pattern are sometimes found, especially when lubrication is inadequate
and/or “slip-stick” conditions occur between the tablet and the die wall, owing to continuing
formation and breakage of tablet/die-wall adhesions.
 Worn dies, which cause the bore to become barrel-shaped, give rise to a similar abnormal
ejection force trace and may lead to failure of the tablet structure.
 A direct connection is to be expected between die wall frictional forces and the force
required to eject the tablet from the die, FE. For example, well lubricated systems (as
indicated by a large R value) have been shown to lead to smaller FE values.
FORCE-VOLUME RELATIONSHIPS
 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.
 The two terms on the right side of the equation refer to steps (1) and (2) respectively.
 Although equation so far has only been shown to fit data from a few materials (such as
alumina and magnesia), it does establish that the degree of compression achieved for a given
load depends upon the initial porosity (E0).
 Therefore, the common practice of comparing different formulations by means of testing
tablets of the same weight is undesirable.

20
 One variable is eliminated if experiments are carried out on tablet masses of the same true
volume, and allowance should be made for varying initial values of bulk volume (Vb) when
interpreting the results.
 A more complex sequence of events during compression involves four stages, as illustrated
by the data in Fig.
 (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 stage iv occur.
 (stage iv) compression of the solid crystal lattice, occurs.

 Attempts that have been made to derive equations for the first three stages, are of limited
value, because in practice, the stages are not totally sequential.
 Owing to transmitted force variation, they may occur simultaneously in different regions
of the same tablet.
 In many tabletting processes, however, once appreciable force has been applied, the
relationship between applied pressure (P) and some volume parameter such as porosity €
does become linear over the range of pressure commonly used in tabletting (region iii in
Fig).
 For example, an equation first suggested by Shapiro has been shown to fit data obtained
from several pharmaceutical materials:
 Log E = Log E0 – K.P

21
 where, E0 is the porosity when the pressure is zero, and K is a constant. Another equation
for which there is considerable evidence, is attributed to Walker:

 Heckel Plots
 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

(Ky = 1/3S), and Kr is related to the initial repacking stage, and hence E0.
 The above relationships 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:

22
 where, w is the weight of the tabletting mass, ρt is its true density, and H is the thickness
of the tablet at that point (obtained from the relative punch displacement measurements).
(See previous section, “Mass-Volume Relationships”).
 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 in turn is influenced by the size distribution, shape, etc. of the original particles.
Heckel plots for such materials are shown by type ‘a’ in Fig ; 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’ in Fig. 13.47 shows Heckel plots for different size fractions of the same
material that are typical of this behavior. Lactose is one such material.
 Type ‘a’ Heckel plots usually exhibit a higher final slope (Ky) than type ‘b’, which
implies that the former materials have 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.

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 The two regions of the Heckel plot are thought to represent the initial repacking stage and
the subsequent deformation process, the point of intersection corres-ponding 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.
 Note that 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.
 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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  In addition to the predictive capability, establishing behavioural patterns for a given
formulation (so-called “fingerprinting”) may provide valuable diagnostic information in
the event that a particular batch of the product causes problems.
 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.
DECOMPRESSION
 In operations such as tabletting, the compressional process is followed by a decompression
stage, as the applied force is removed.
 This leads to a new set of stresses within the tablet as a 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.
 For this reason, studies in which data are collected during both parts of the cycle have
proved valuable.
 In particular, the degree and rate of relaxation within tablets, immediately after the point of
maximum compression, have been shown to be characteristic for a particular system.
 Recording this phase of the cycle as well can provide valuable insight into the reasons
behind inferior tablet quality and may suggest a remedy.
 For example, if the degree and rate of relaxation are high, addition of some plastically
deforming component, such as polyvinyl pyrrolidone, may be advisable to reduce the risk of
pronounced recovery leading to structural failure.
 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 in series. This
interpretation leads to a relationship of the form:
Log Ft = Log Fm – Kt

25
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 (i.e. when decompression begins). 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 tabletting mass due to the compactional force,
and subsequently due to elastic recovery during unloading, can be used to obtain a measure
of plastoelasticity, specifically:
H 0 H r −Hm
γ= ⋅
Hm H 0 −H m

where, Ho, 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 γ and log reciprocal of the tensile strength of the tablets has
been demonstrated.
 In general, values of γ above 9 tend to produce tablets that are laminated or capped.
 Compaction Profiles
 Monitoring of that proportion of the applied pressure transmitted radially to the die wall has
been reported by several groups of workers.
 For many pharmaceutical materials, such investigations lead to characteristic hysteresis
curves, which have been termed compaction profiles. Fig. is a typical example.
 Remember that the radial die-wall force arises as a result of the tabletting 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.
 The ratio is a property of solid bodies, however, and not necessarily of a porous mass of
particulate solid.
 The anomalous results discussed in the literature may well reflect this important distinction,
but certain qualitative deductions may still be possible.

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 For instance, 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 upon the value of the material’s modulus of elasticity (Young’s modulus).
 If this value is low, there is considerable recovery, and unless a strong structure has been
formed, there is the danger of structural failure.
 Maximum compressional force levels are particularly important in such cases, since most of
the stored energy is released on removal of the applied load.
 Conversely, if the modulus of elasticity is high, there is a small dimensional change on
decompression and less risk of failure.
 The area of the 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 tabletting 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:
PR = PA – 2S
where, S is the yield strength of the material.
 Note that the slope of this plot is unity, so that marked deviation from this value may
indicate a more complex behavior.

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 Deviation could also be due to the fact that the material is still significantly porous, which
would invalidate the analogy to a solid body.
 Until this difference can be resolved, little is to be gained in proposing mathematical
solutions for the region BC, which is often nonlinear anyway.
 This does not mean, however, that compaction profiles themselves cannot provide further
useful information.
 For example, since point C represents the situation at the maximum compressional force
level, the region CD is therefore the initial relaxation response as the applied load is
removed.
 In practice, many compaction profiles exhibit a marked change in the slope of this line
during decompression, and a second yield point (point D) has been reported.
 Perhaps the residual radial pressure (intercept EO), when all the compressional force has
been removed, is more significant, since this pressure is an indication of the force being
transmitted by the die wall to the tablet.
 As such, it provides a measure of possible ejection force level and likely lubricant
requirements; if pronounced, it suggests a strong tablet capable of at least withstanding
such a compressive pressure.
 Conversely, a low value of residual radial pressure, or more significantly, a sharp change
in slope (DE) is sometimes indicative of at least incipient failure of the tablet structure.
 In practical terms, this may mean introducing a plastically deforming component (e.g.
PVP [polyvinylpyrrolidone] as binder, starch as diluent) to facilitate dissipation of these
stresses, and hence a more gradual change in slope of the decompression plot, a preferred
feature.
 In one recent study, modified compaction profiles (PA – PR) versus (PA + PR) were able
to distinguish between readily consolidating and no consolidating materials.
 Specifically, two characteristic parameters (a normal stress value at zero shear and a
minimum shear stress value), obtained from the unloading portion of the cycle, were
shown to correlate with tensile strength and surface hardness of the compacted materials.

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 ENERGY INVOLVED IN COMPACTION
 Tablet machines, roll compactors, extruders, and similar types of equipment require a
high input of mechanical work.
 The ways in which this work is converted into other forms of energy during these
processes is of interest in both research and production areas.
 More specifically, the work requirement is a key factor in machine design, and any
proportion of the applied energy stored in a product such as a tablet retains a destructive
capability.
 The work involved in various phases of a tablet or granule compaction operation includes
(1) that necessary to overcome friction between particles,
 (2) that necessary to overcome friction between particles and machine parts,
 (3) that required to induce elastic and/or plastic deformation of the material,
 (4) that required to cause brittle fracture within the material and
 (5) that associated with the mechanical operation of various machine parts.
 Normally, an appreciable amount of the energy supplied is converted to heat, which of
course does not contribute toward the main objective of the process.
 On a theoretic basis, however, this heat does provide a means of monitoring the energy
balance in the system.
 For example, one of the earliest experimental reports was that of Nelson and associates,
who compared the energy expenditure in lubricated and unlubricated sulfathiazole
granulations as shown in Table.
Energy expanded in compression of 400mg sulfathiazole granulation
Compression process Energy Expanded (joules)
Unlubricated Lubricated
Compression 6.28 6.28
Overcoming die wall friction 3.35 negligible
Upper punch withdrawal 5.02 negligible
Tablet ejection 21.35 2.09
Total 36.00 8.37
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 Lubrication reduced energy expenditure by 75%, chiefly because of a lessening of the
major component, namely energy utilized during ejection of the finished tablet.
 Note that lubrication has no apparent effect on the actual amount of energy required to
compress the material, i.e. overcome resistance to relative interparticulate movement.

 These workers’ estimation of the total work involved, WT, was obtained by monitoring
punch force and the distance D through which it acted, so that:
 which represents the area under the entire force-displacement plot (the area ABC in Fig).

 Example of force-displacement (F-D) curve. (▵) upper punch force; (▴) lower punch
force. The area WF represents the work done in overcoming friction, while that of area
WD is the elastic deformation energy stored in the tablet during compression. Thus, WN
is the net mechanical energy actually used to form the tablet
 This approach oversimplifies the true picture because, as can be seen from Fig. 13.49, in
which both punch forces and punch displacement data have been collected throughout an
entire compression-decompression press cycle, WT comprises at least three components.
 The region WF represents the work done in overcoming friction and therefore depends
upon the properties of the tablet mass.
 WN is the net mechanical energy actually used to form the tablet, and WD is the elastic
deformation energy stored in the tablet initially, but released during decompression.
 If the top punch moves too quickly during this decompression, contact with the tablet
may be lost.
 In this eventuality, the complete work of elastic recovery of the tablet is not transferred to
the punch face, and an error is introduced into the decompression curve.
 Early investigators of the technique overcame the problem by compressing the tablet a
second time before ejecting it from the die.
 The second compression-decompression cycle provides a measure (WN2) of the net
energy required to recompress the material to the point B (in Fig. 13.49).

30
  WN2 is equivalent to the amount of energy involved in the elastic recovery of the tablet.
 Force-displacement (F-D) Curves
 Distinctive F-D curves related to the stress/strain properties of the materials involved
have now been reported by several groups of workers.
 The technique has been shown to provide a more sensitive method for evaluating
lubricant efficiency than the widely quoted R value (which is the lower to upper punch
force ratio).
 For example, the data given in Table 13.13 show that R values are incapable of
distinguishing between the result of incorporating lubricant in the granulation and the
result of coating it on the die wall.
 The WN measurements, however, clearly indicate the lower energy expenditure if the
granulation is lubricated.
Compression of 300mg at 440 MPa
Unlubricated Die wall Granulation
lubricated lubricated
Coefficient of lubrication, R 0.84 0.98 0.98
Network of compression (Nm) 5.6 4.4 3.4
Remaining lower punch pressure 3.2 2.5 2.5
(MPa)

 The wider utility of F-D curves is exemplified by their application to the selection of a
“best” binder (from gelatin, starch, and methylcellulose) for a sulphonamide tablet, by
determining the contribution of the three components WF, WN, and WD to the total work
WT.
 A plot of WN versus maximum compressional force produced curves such as those
shown in Fig. 13.50.
 Since good correlation is usually found between WN and the crushing strength of the
tablets, gelatin in this example would be chosen as the best binder.

31
 Note to the pronounced flattening of the curve for starch, so that compression of this
formulation at maximum FA values above the point of inflection would not be helpful
and might even be deleterious, owing to increased elastic recovery that could lead to

structural failure of the tablet.

 Because the rate of compression is known to affect the tabletting process, an extension of
the use of F-D curve data has been suggested.
 This proposition takes into account the rate of loading by monitoring the power
expended, rather than the work involved.
 In practice, the area under the F-D curve is divided by the time over which the force is
applied.

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