Tablet CompressionTablet Compression

Compression: Compression: Compression is the process of applying pressure to the Compression is the process of applying pressure to the

powder material for the reduction of the bulk volume, to give powder material for the reduction of the bulk volume, to give a solid matrix.a solid matrix.

Compressibility:Compressibility: It is the ability of the powder to decrease inIt is the ability of the powder to decrease involume under pressure (due to applicationvolume under pressure (due to applicationof a given stress.)of a given stress.)

.. CompactionCompaction : Compaction is the situation in which powders are subjected to some level of mechanical force.: Compaction is the situation in which powders are subjected to some level of mechanical force.

CompactionCompaction:: Compaction of powder is the general term used Compaction of powder is the general term used

to described the situation in which powders to described the situation in which powders are subjected to some level of mechanical are subjected to some level of mechanical force.force.

That is, the transformation of a powder into a That is, the transformation of a powder into a coherent specimen of defined shape by powder coherent specimen of defined shape by powder compression compression

Compatibility:Compatibility:It is the ability of the powder bed to cohere into It is the ability of the powder bed to cohere into or to form a compact. or to form a compact.

The forces involved during compaction of The forces involved during compaction of powders powders

Fa = Maximum upper punch force Fa = Maximum upper punch force applied to compact.applied to compact.

Fb = Maximum force transmitted to Fb = Maximum force transmitted to lower punch by compact.lower punch by compact.

Fd = Force lost to the die wall.Fd = Force lost to the die wall. Fr = Maximum radial force at die wall Fr = Maximum radial force at die wall

during compaction.during compaction.

1. Particle rearrangement1. Particle rearrangement 2. Elastic deformation2. Elastic deformation 3. Plastic deformation of particles3. Plastic deformation of particles 4. Fragmentation of particles4. Fragmentation of particles 5. Formation of interparticulate 5. Formation of interparticulate

bondsbonds 6. Ejection6. Ejection

Frictional forceFrictional forceTwo major components to the frictional forces are:Two major components to the frictional forces are: Interparticulate friction-: This arise at particulate Interparticulate friction-: This arise at particulate

contacts and can be expressed in terms of a coefficient contacts and can be expressed in terms of a coefficient of interparticulate friction μ1. It is more significant at of interparticulate friction μ1. It is more significant at low applied loads.low applied loads.

Materials that reduce this effect are referred to as Materials that reduce this effect are referred to as glidants, colloidal silica.glidants, colloidal silica.

Die wall friction-:Die wall friction-:This results from material being pressed against the die This results from material being pressed against the die

wall and moved down it. It is expressed as μ2., the wall and moved down it. It is expressed as μ2., the coefficient of die wall friction. This effect is dominant at coefficient of die wall friction. This effect is dominant at high applied forces when particle rearrangement has high applied forces when particle rearrangement has ceased and is particularly important in tabletting ceased and is particularly important in tabletting operation. operation.

Lubricant such as Magnesium stearate is used to reduce.Lubricant such as Magnesium stearate is used to reduce.

Force distributionForce distribution..Shown in fig X. Shown in fig X. FA = FL + FFA = FL + FD (1) (1) Where FA is the force applied to the upper punch, Where FA is the force applied to the upper punch, FL is that proportion of it transmitted to the lower punch, FL is that proportion of it transmitted to the lower punch, FD is a reaction at the die wall due to friction at the surface. FD is a reaction at the die wall due to friction at the surface.

Because of the inherent difference between the force applied at Because of the inherent difference between the force applied at the upper punch and that affecting material close to the lower the upper punch and that affecting material close to the lower punch , a more compaction force, FM, has been proposed., punch , a more compaction force, FM, has been proposed., where where

FA + FLFA + FL FM = --------------- (2)FM = --------------- (2) 22

In single –station presses, where the In single –station presses, where the applied force transmission decays applied force transmission decays exponentially, a more appropriate exponentially, a more appropriate geometric mean force, Fc, might be geometric mean force, Fc, might be

FG = (FA . FL)FG = (FA . FL)0.5

Use of these force parameters are Use of these force parameters are probably more appropriate than use of FA, probably more appropriate than use of FA, when determining relationships between when determining relationships between compressional force and such tablet compressional force and such tablet properties as tablet strength.properties as tablet strength.

Development of Radial Force Development of Radial Force As the compressional force is increased and any As the compressional force is increased and any

repacking of the tabletting mass is completed, the repacking of the tabletting mass is completed, the material may be regarded to some extent as a single material may be regarded to some extent as a single body. body.

In the case of an unconfined solid body this would be In the case of an unconfined solid body this would be accompanied by an expansion in the horizontal accompanied by an expansion in the horizontal direction of ∆D.direction of ∆D.

The ratio of these two dimensional changes is known as The ratio of these two dimensional changes is known as the the poisson ratio λpoisson ratio λ of the material, defined as of the material, defined as

Λ = ∆D /∆HΛ = ∆D /∆H

This ratio is a characteristic constant for This ratio is a characteristic constant for each solid and may influence the tabletting . each solid and may influence the tabletting .

Shown in fig-X, the material is not free to Shown in fig-X, the material is not free to expand in the horizontal plane, a radial die expand in the horizontal plane, a radial die wall force Fwall force FR is developed perpendicular to is developed perpendicular to the die wall surface.the die wall surface.

materials with larger poisson ratio giving materials with larger poisson ratio giving rise to higher Frise to higher FR. Then classic theory can . Then classic theory can then be applied to deduce that the axial then be applied to deduce that the axial friction force FD related to the FR by the friction force FD related to the FR by the expressionexpression

FFD = μ = μww . F . FR (5) (5)

Where μw, is the coefficient of the die Where μw, is the coefficient of the die wall friction.wall friction.

It is noted that FIt is noted that FR is reduced when is reduced when materials of small poisson ratio are used materials of small poisson ratio are used and that in such case, axial force and that in such case, axial force transmission is optimumtransmission is optimum..

A common method of comparing A common method of comparing degrees of lubrications has been to degrees of lubrications has been to measure the applied and transmitted measure the applied and transmitted axial forces and determine the Faxial forces and determine the FL / / FFAA. .

This is called the coefficient of This is called the coefficient of lubricant efficiency, or R value. The lubricant efficiency, or R value. The ratio approaches unity for perfect ratio approaches unity for perfect lubrication (no wall friction). Values lubrication (no wall friction). Values below 0.8 probably indicates a poor below 0.8 probably indicates a poor lubricationlubrication

Die wall lubricationDie wall lubrication Tablet formulation require the addition of a Tablet formulation require the addition of a

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

Perfectly there is some chemical bonding Perfectly there is some chemical bonding between the boundary lubricant and the between the boundary lubricant and the surface of the die wall as well as at the edge surface of the die wall as well as at the edge of the tablet.of the tablet.

The best lubricants are those with low shear The best lubricants are those with low shear strength but strong cohesive tendencies In strength but strong cohesive tendencies In directions at right angles to the plane of directions at right angles to the plane of shear.shear.

Ejection ForcesEjection Forces The force necessary to eject a finished tablet The force necessary to eject a finished tablet

follows a a distinctive patern of three stages:follows a a distinctive patern of three stages: -The first stage involves the distinctive peak force -The first stage involves the distinctive peak force

required to initiate ejection, by breaking tablet /die required to initiate ejection, by breaking tablet /die wall adhesion.wall adhesion.

-A smaller force usually follows namely that -A smaller force usually follows namely that required to push the tablet up the die wall.required to push the tablet up the die wall.

-The final stage is marked by declining force of -The final stage is marked by declining force of ejection as the tablet emerges from the die wall.ejection as the tablet emerges from the die wall.

Variables on this pattern are sometimes found Variables on this pattern are sometimes found especially when lubrication is inadequate and/or especially when lubrication is inadequate and/or Slip-stick condition occur between the tablet and Slip-stick condition occur between the tablet and die wall.die wall.

The forces involved during compaction of The forces involved during compaction of powders powders

Fa = Maximum upper punch force applied Fa = Maximum upper punch force applied to compact.to compact.

Fb = Maximum force transmitted to lower Fb = Maximum force transmitted to lower punch by compact.punch by compact.

Fd = Force lost to the die wall.Fd = Force lost to the die wall. Fr = Maximum radial force at die wall Fr = Maximum radial force at die wall

during compaction.during compaction.

Upper punchUpper punch

Fa ↓Fa ↓

. . . . . . . . . .. . . . . . . .. . .. ←←.Fr . .Fr . . . . . . . . . FdFd compact ←. . . . ↓Fb. .compact ←. . . . ↓Fb. .

Lower punchLower punch FigFig: : Forces involved in compactionForces involved in compaction

The physics of compaction is the The physics of compaction is the compression and consolidation of two compression and consolidation of two phases system (particulate solid-gas) due phases system (particulate solid-gas) due to the applied force.to the applied force.

Consolidation:Consolidation:Due to particle-particle interaction, the Due to particle-particle interaction, the mechanical strength of the material is mechanical strength of the material is increased, which consolidates the material increased, which consolidates the material into a single solid matrix. This phenomena into a single solid matrix. This phenomena is called consolidation. is called consolidation.

Decompression:Decompression:#During tablet manufacturing, the #During tablet manufacturing, the

compressional process is followed by a compressional process is followed by a decomposition stage when the applied decomposition stage when the applied force is removed.force is removed.

# So as a result of elastic recovery, a new # So as a result of elastic recovery, a new force is developed within the tablet which force is developed within the tablet which is augmented by the forces necessary to is augmented by the forces necessary to eject the tablet from the die wall.eject the tablet from the die wall.

Deformation:Deformation: When a solid body is subjected to an When a solid body is subjected to an

opposite force, its geometry is changed opposite force, its geometry is changed depending on the nature of the force and depending on the nature of the force and the change in geometry is called the change in geometry is called deformation.deformation.

There are 2 types of deformation-There are 2 types of deformation- Elastic deformationElastic deformation Plastic deformationPlastic deformation

Powder particlesPowder particles RepackingRepacking Deformation particles(due to Deformation particles(due to

compressioncompression

if compressive force is removedif compressive force is removed Elastic deformationElastic deformation plastic plastic

deformationdeformation particles return to theirparticles return to their particles particles

retain in deformation conditionretain in deformation condition

Elastic deformation:Elastic deformation: In elastic deformation, the deformed In elastic deformation, the deformed

materials return to their initial shape. materials return to their initial shape. ( deformation disappears completely)( deformation disappears completely)

All solids undergo / show elastic All solids undergo / show elastic deformation when external force is deformation when external force is applied but the force must be within the applied but the force must be within the range.range.

Example:Example: Aspirin, Aspirin, Cohesion is lost.Cohesion is lost.

:: Plastic deformationPlastic deformation Here, the deformed materials don’t return to Here, the deformed materials don’t return to

their initial shape (deformation doesn’t their initial shape (deformation doesn’t completely recover after release of stress).completely recover after release of stress).

Time independent, permanent deformation of a Time independent, permanent deformation of a particle. Degree of deformation is thus particle. Degree of deformation is thus controlled by applied pressure and controlled by applied pressure and independent of the time of loading.independent of the time of loading.

Deformation occurs without a change in particle Deformation occurs without a change in particle volume.volume.

The materials in which – The materials in which – Shear strength< tensile or breaking Shear strength< tensile or breaking

strength, will show plastic deformation. But strength, will show plastic deformation. But when - shear strength> tensile or breaking when - shear strength> tensile or breaking strength, particles becomes fractured and strength, particles becomes fractured and fragmented. Then fragmented smaller fragmented. Then fragmented smaller particles will fill up the adjacent air space particles will fill up the adjacent air space and helps the compression process.and helps the compression process.

Example: ‘Sucrose’ behaves like that way.Example: ‘Sucrose’ behaves like that way. Cohesion is retained (among the particles)Cohesion is retained (among the particles)

Shear strength< tensile or breaking Shear strength< tensile or breaking strength, will show plastic deformation.strength, will show plastic deformation.

But when - shear strength> tensile or But when - shear strength> tensile or breaking strength, particles becomes breaking strength, particles becomes fractured and fragmented. Then fragmented fractured and fragmented. Then fragmented smaller particles will fill up the adjacent air smaller particles will fill up the adjacent air space and helps the compression process.space and helps the compression process.

Example: ‘Sucrose’ behaves like that way.Example: ‘Sucrose’ behaves like that way. Cohesion is retained (among the particles)Cohesion is retained (among the particles)

Irrespective of the behavior of Irrespective of the behavior of large particles, of the materials, large particles, of the materials, small particles may deform small particles may deform plastically, a process known as plastically, a process known as micro-squashing and the micro-squashing and the proportion of fine particles in a proportion of fine particles in a sample may therefore be sample may therefore be significant.significant.

Mechanism of compression:Mechanism of compression: An appropriate volume of granules are fed An appropriate volume of granules are fed

into a die cavity.into a die cavity. ↓↓ Granules are compressed between an Granules are compressed between an

upper and a lower punchupper and a lower punch ↓↓ Consolidation of materials / granules into a Consolidation of materials / granules into a

single solid matrixsingle solid matrix ↓↓ Tablets are ejected from the die cavity.Tablets are ejected from the die cavity.

Process of compression:Process of compression:

Spherical particles undergo less particle Spherical particles undergo less particle rearrangement than irregular particles, as rearrangement than irregular particles, as spherical particles undergo a close packing spherical particles undergo a close packing initially.initially.

* To achieve the fast flow rate for high speed * To achieve the fast flow rate for high speed compression, granulation is performed to compression, granulation is performed to produce spherical or oval particles. That’s produce spherical or oval particles. That’s why; particle rearrangement and energy why; particle rearrangement and energy expended in rearrangement are minor expended in rearrangement are minor consideration in the total process of consideration in the total process of compression.compression.

Deformation at points of contact:Deformation at points of contact:

When force is applied to a material, 2 types of When force is applied to a material, 2 types of deformation occur: deformation occur: Elastic deformation, Plastic Elastic deformation, Plastic deformation.deformation.

The force required to initiate a plastic deformation The force required to initiate a plastic deformation is called yield stress.is called yield stress.

When the particles of the granulation are closely When the particles of the granulation are closely packedpacked

↓ ↓ No further filling of void space can occurNo further filling of void space can occur ↓ ↓ Further ↑ of compressional force causes Further ↑ of compressional force causes

deformation at the points of contactdeformation at the points of contact

A = Loose packing B = Close packing, C A = Loose packing B = Close packing, C = Elastic deformation D = Plastic = Elastic deformation D = Plastic deformation, E = Brittle fracturedeformation, E = Brittle fracture

Fig: Graphical representation of Fig: Graphical representation of elastic & plastic deformation.elastic & plastic deformation.

Deformation Deformation ↑es the area of true ↑es the area of true contactcontact ↑ ↑es the area of potential es the area of potential bondingbonding

Fragmentation & Fragmentation & deformation:deformation:

At higher pressure, fragmentation occurs At higher pressure, fragmentation occurs within the particles.within the particles. ↓↓

Fragmentation ↑es the number of Fragmentation ↑es the number of particles and new surface area.particles and new surface area.

↓ ↓ So density of the material further So density of the material further

increased.increased.↓↓DeformationDeformation

Bonding:Bonding:3 theories of bonding are-:3 theories of bonding are-: Mechanical theoryMechanical theory Intermolecular theoryIntermolecular theory Liquid – surface film theoryLiquid – surface film theory

A. Mechanical theoryA. Mechanical theory

Under pressure, particles undergo elastic Under pressure, particles undergo elastic deformation, plastic deformation, brittle deformation, plastic deformation, brittle deformation.deformation.↓↓

Mechanical bond is formed through the edges Mechanical bond is formed through the edges of the particles.of the particles.

*If only mechanical bond exists, then-*If only mechanical bond exists, then-Total energy of compression = deformation Total energy of compression = deformation

energy + heat + energy absorbed by each energy + heat + energy absorbed by each particle.particle.

B. Intermolecular force B. Intermolecular force theorytheory

Under pressure, molecules remain at the Under pressure, molecules remain at the points of true contact, between the new points of true contact, between the new surfaces of the particles.surfaces of the particles.Vander waals force is activated.Vander waals force is activated.↓↓

Consolidations of particles occur.Consolidations of particles occur. ExampleExample:: Microcrystalline cellulose – “cellulose crystals” Microcrystalline cellulose – “cellulose crystals”

remain in close contact by H-bonding remain in close contact by H-bonding

C. Liquid – surface film C. Liquid – surface film theory:theory:

Here bonding occurs through a thin Here bonding occurs through a thin liquid film (which is the consequence liquid film (which is the consequence of fusion or solution) at the surface of of fusion or solution) at the surface of the particle.the particle.

The bonding is induced by the The bonding is induced by the energy of compression.energy of compression.

During compression an applied force During compression an applied force is exerted on the granules, but is exerted on the granules, but locally the force is applied to a small locally the force is applied to a small area of true contact and for this a area of true contact and for this a very high pressure exists at the true very high pressure exists at the true contact surface. The local effect of contact surface. The local effect of the high pressure on the melting the high pressure on the melting point and solubility of a material is point and solubility of a material is essential for bonding.essential for bonding.

*Hot welding:*Hot welding: Most particles in the powder bed have irregular shape and Most particles in the powder bed have irregular shape and

for this they have many points of contact.for this they have many points of contact. ↓↓ When pressure is applied, it may produce frictional heat.When pressure is applied, it may produce frictional heat. ↓↓ If heat is not dissipated, local rise in temperature may If heat is not dissipated, local rise in temperature may

cause the melting of contact area of the particles.cause the melting of contact area of the particles. ↓↓ Then stress in that particular area is relieved and melt Then stress in that particular area is relieved and melt

solidities, giving rise to fusion bonding.solidities, giving rise to fusion bonding. ↓↓ And at last, the mechanical strength of the mass is ↑ed.And at last, the mechanical strength of the mass is ↑ed.

*cold welding: *cold welding:

When the surfaces of two particles When the surfaces of two particles approach each other closely enough approach each other closely enough (e. g. at a separation of less than 50 (e. g. at a separation of less than 50 nm), their free surface energies nm), their free surface energies result in a strong attractive force , a result in a strong attractive force , a process known as cold welding.process known as cold welding.

solubility ∞ Pressuresolubility ∞ Pressure Surface of granules during compression, the Surface of granules during compression, the

solubility of true contact are or is increased with solubility of true contact are or is increased with increasing pressure.increasing pressure.

↓↓ When pressure is released, solubility is decreased.When pressure is released, solubility is decreased. ↓↓ Solutes dissolved in the adsorbed water, or present Solutes dissolved in the adsorbed water, or present

in the solution, crystalline into small crystals in the solution, crystalline into small crystals between the particles.between the particles.

↓↓ So, the mechanical strength of the mass is ↑ed.So, the mechanical strength of the mass is ↑ed.

The mechanical strength of the mass The mechanical strength of the mass depends on – depends on – The amount of material depositedThe amount of material deposited

The rate of crystallizationThe rate of crystallization*Both hot and cold welding depend on *Both hot and cold welding depend on

several factors- several factors- The chemical nature of the materialThe chemical nature of the materialThe extent of contact areaThe extent of contact areaThe presence of surface contaminationsThe presence of surface contaminationsThe inter-surface distanceThe inter-surface distance

Decompression:Decompression: In tablet manufacturing, compressional In tablet manufacturing, compressional

process is applied followed by a process is applied followed by a decompression stage, as the applied decompression stage, as the applied pressure is removed.pressure is removed.

Decompression leads a new set of stresses Decompression leads a new set of stresses within the tablet as a result of elastic within the tablet as a result of elastic recovery, which is augmented by the recovery, which is augmented by the forces necessary to eject the tablet from forces necessary to eject the tablet from the die cavity.the die cavity.

During decompression, as the upper During decompression, as the upper punch is withdrawn from the die punch is withdrawn from the die cavity, the tablet is confined in the cavity, the tablet is confined in the die by a radial pressure. But if only die by a radial pressure. But if only elastic deformation s occurred due to elastic deformation s occurred due to sudden removal of axial pressure, sudden removal of axial pressure, then the granules will return to their then the granules will return to their original form by breaking any bonds original form by breaking any bonds that was formed under pressure.that was formed under pressure.

As the movement of the tablet is restricted As the movement of the tablet is restricted by the die wall pressure and the friction with by the die wall pressure and the friction with the die wall, the stress from axial elastic the die wall, the stress from axial elastic recovery and radial contraction causes the recovery and radial contraction causes the splitting of the tablet unless the shear stress splitting of the tablet unless the shear stress is relieved by plastic deformation.is relieved by plastic deformation.

But stress relaxation by plastic deformation But stress relaxation by plastic deformation is time dependent. Materials having slow is time dependent. Materials having slow rates of stress relaxation, cracking occur in rates of stress relaxation, cracking occur in the die during compression.the die during compression.

Example:Example: Paracetamol – Rate of stress relieve Paracetamol – Rate of stress relieve

is slow.is slow. So, cracking occurs while So, cracking occurs while

the tablet is within the die.the tablet is within the die. Microcrystalline cellulose - Microcrystalline cellulose - Rate Rate

of stress relieve is rapidof stress relieve is rapid So, no cracking So, no cracking

occurs.occurs.

Ejection:Ejection: Ejection is the last stage of tablet Ejection is the last stage of tablet

compression.compression. As the lower punch rises and pushes As the lower punch rises and pushes

the tablet upward, there is a the tablet upward, there is a continued residual die wall pressure continued residual die wall pressure and considerable energy may be and considerable energy may be expanded due to die wall friction.expanded due to die wall friction.

As the tablet is removed from the As the tablet is removed from the die,die,

Lateral pressure is Lateral pressure is relivedrelived

Tablet undergoes Tablet undergoes elastic recoveryelastic recovery

Radial and longitudinal Radial and longitudinal relaxation occursrelaxation occurs

`̀ (2 – 10) % of tablet (2 – 10) % of tablet volume is ↑ed.volume is ↑ed.

Stages in the compression Stages in the compression processprocess

Initially, the particles in the die are rearranged Initially, the particles in the die are rearranged resulting in a closer packing structure.resulting in a closer packing structure.

At a certain load, the packing characteristics of At a certain load, the packing characteristics of the particles or a high interparticulate friction the particles or a high interparticulate friction between particles will prevent any further between particles will prevent any further interparticulate movement.interparticulate movement.

The subsequent reduction of compact volume The subsequent reduction of compact volume is therefore accompanied by elastic and plastic is therefore accompanied by elastic and plastic deformation of the initial particles.deformation of the initial particles.

For many materials these particles are For many materials these particles are then fragmented.then fragmented.

Fragmentation can be defined as a Fragmentation can be defined as a dividing up of a particle into number dividing up of a particle into number of smaller, discrete parts. of smaller, discrete parts.

The particle fragment will then The particle fragment will then normally find new positions, which will normally find new positions, which will further decrease the compact volume.further decrease the compact volume.

When the applied pressure is further When the applied pressure is further increased, the smallest particles formed increased, the smallest particles formed could again undergo deformation.could again undergo deformation.

Thus a single particle may pass through Thus a single particle may pass through one or several of these processes several one or several of these processes several times during a compression..times during a compression..

As a consequence of the compression of As a consequence of the compression of the powder, particle surfaces are brought the powder, particle surfaces are brought into close to each other and into close to each other and interparticulate attraction or bonds will be interparticulate attraction or bonds will be formed.formed.

In summaryIn summary 1. Particle rearrangement1. Particle rearrangement 2. Elastic deformation2. Elastic deformation 3. Plastic deformation of particles3. Plastic deformation of particles 4. Fragmentation of particles4. Fragmentation of particles 5. Formation of interparticulate 5. Formation of interparticulate

bondsbonds EjectionEjection

Examples of materials consolidating Examples of materials consolidating by plastic deformation are Sodium by plastic deformation are Sodium Chloride, starch. Fragmenting Chloride, starch. Fragmenting materials are, for example, materials are, for example, crystalline lactose, sucrose.crystalline lactose, sucrose.

However all materials posses both an However all materials posses both an elastic and a plastic components.elastic and a plastic components.

The volume reduction mechanism The volume reduction mechanism which will dominate for a specific which will dominate for a specific material is dependent on factors such material is dependent on factors such as temperature and compression rate.as temperature and compression rate.

Lower temperatures and faster Lower temperatures and faster loading during compression will loading during compression will generally facilitate consolidation by generally facilitate consolidation by fragmentation.fragmentation.

Ejection:Ejection:

Ejection is the last stage of tablet Ejection is the last stage of tablet compression.compression.

As the lower punch rises and pushes As the lower punch rises and pushes the tablet upward, there is a the tablet upward, there is a continued residual die wall pressure continued residual die wall pressure and considerable energy may be and considerable energy may be expanded due to die wall friction.expanded due to die wall friction.

As the tablet is removed from the die,As the tablet is removed from the die, Lateral pressure is relivedLateral pressure is relived Tablet undergoes elastic recoveryTablet undergoes elastic recovery Radial and longitudinal relaxation Radial and longitudinal relaxation

occursoccurs `̀ (2 – 10) % of tablet volume is (2 – 10) % of tablet volume is

↑ed.↑ed.

F′ = Normal force to die wall during ejection.F′ = Normal force to die wall during ejection. Fe = Maximum lower punch force to initiate ejection.Fe = Maximum lower punch force to initiate ejection.

F′F′ FeFe Fig: Forces at the start of ejection.Fig: Forces at the start of ejection. ← ← RR →RR → ↑↑LrLr

LpLp Fig: Elastic recovery dFig: Elastic recovery d

Primary and Secondary factors for tablets Primary and Secondary factors for tablets strengthstrength

Two factors are regarded as primary factors Two factors are regarded as primary factors for the compactability of powder are : a. for the compactability of powder are : a. the the dominating bond mechanism and b. the dominating bond mechanism and b. the surface area surface area overwhich these bonds are overwhich these bonds are active.active.

More indirect , secondary factors are More indirect , secondary factors are normally studied and used for correlation normally studied and used for correlation with tablet strength. These are , with tablet strength. These are , particle particle shape, surface texture and particle size.shape, surface texture and particle size.

Bonding surface areaBonding surface area

The term bonding surface area is The term bonding surface area is often defined as the effective often defined as the effective surface area taking part in the surface area taking part in the interparticulate attraction.interparticulate attraction.

In case of solid bridges, the term In case of solid bridges, the term corresponds to the true corresponds to the true interparticulate contact area, interparticulate contact area, while for intermolecular forces while for intermolecular forces the term is difficule to define.the term is difficule to define.

Bonding MechanismsBonding Mechanisms

Mainly five typesMainly five types 1. Solid bridges (melting, crystallization, 1. Solid bridges (melting, crystallization,

chemical reactions, and hardened chemical reactions, and hardened binders)binders)

2. Bonding due to movable liquids 2. Bonding due to movable liquids (capillary and surface tension forces)(capillary and surface tension forces)

3. Non-freely movable binder bridges 3. Non-freely movable binder bridges (viscous binders and adsorption layers)(viscous binders and adsorption layers)

4. Attraction between particles4. Attraction between particles 5. Shape related bonding (mechanical 5. Shape related bonding (mechanical

interlocking)interlocking)

However, the dominating bonds types However, the dominating bonds types adhering particles together in adhering particles together in compression of dry powder could for compression of dry powder could for simplicity be limited to three types.simplicity be limited to three types.

1. Solid brides (due to e. g. melting)1. Solid brides (due to e. g. melting) 2. Distance attraction (intermolecular 2. Distance attraction (intermolecular

forces)forces) 3. Mechanical interlocking (between 3. Mechanical interlocking (between

irregularly shaped particle)irregularly shaped particle)

The term intermolecular forces includes The term intermolecular forces includes van der Waals forces, electrostatic van der Waals forces, electrostatic forces, and hydrogen bonding.forces, and hydrogen bonding.

The dominant interaction force The dominant interaction force between solid surfaces is the van der between solid surfaces is the van der Waals force of attraction.Waals force of attraction.

This forces operates in vacuum, gas, This forces operates in vacuum, gas, and liquid environment up to a distance and liquid environment up to a distance of 100-10000 A. of 100-10000 A.

Hydrogen bonding is predominantly an Hydrogen bonding is predominantly an electrostatic interaction and may electrostatic interaction and may occur either intermolecularly or occur either intermolecularly or intramolecularly and mainly important intramolecularly and mainly important for many direct compressible binders for many direct compressible binders such as Avicel.such as Avicel.

Electrostatic forces arise during Electrostatic forces arise during mixing and compaction due to mixing and compaction due to triboelectric charging. It is neutralized triboelectric charging. It is neutralized with time by electrostatic discharging.with time by electrostatic discharging.

Solid bridges that contribute to the overall Solid bridges that contribute to the overall compact strength can be defined as areas of compact strength can be defined as areas of real contact i. e. contact at an atomic level real contact i. e. contact at an atomic level between adjacent surfaces in the compact. between adjacent surfaces in the compact. Different types of solid bridges are: Different types of solid bridges are: solid solid bridges due to melting, self diffusion of atoms bridges due to melting, self diffusion of atoms between surfaces, recrystallization of soluble between surfaces, recrystallization of soluble materials in the compacts.materials in the compacts.

It can be measured by electrical resistivity It can be measured by electrical resistivity measurementmeasurement

*Hot welding:*Hot welding: Most particles in the powder bed have irregular Most particles in the powder bed have irregular

shape and for this they have many points of shape and for this they have many points of contact.contact.

↓↓ When pressure is applied, it may produce frictional When pressure is applied, it may produce frictional

heat.heat. ↓↓ If heat is not dissipated, local rise in temperature If heat is not dissipated, local rise in temperature

may cause the melting of contact area of the may cause the melting of contact area of the particles.particles.

↓↓ Then stress in that particular area is relieved and Then stress in that particular area is relieved and

melt solidities, giving rise to fusion bonding.melt solidities, giving rise to fusion bonding. ↓↓ And at last, the mechanical strength of the mass is And at last, the mechanical strength of the mass is

↑ed.↑ed.

*cold welding: *cold welding:

When the surfaces of two particles approach each other When the surfaces of two particles approach each other closely enough (e. g. at a separation of less than 50 nm), closely enough (e. g. at a separation of less than 50 nm), their free surface energies result in a strong attractive their free surface energies result in a strong attractive force , a process known as cold welding.force , a process known as cold welding.

solubility ∞ Pressuresolubility ∞ Pressure Surface of granules during compression, the solubility of Surface of granules during compression, the solubility of

true contact area or is increased with increasing pressure.true contact area or is increased with increasing pressure. ↓↓ When pressure is released, solubility is decreased.When pressure is released, solubility is decreased. ↓↓ Solutes dissolved in the adsorbed water, or present in the Solutes dissolved in the adsorbed water, or present in the

solution, crystalline into small crystals between the solution, crystalline into small crystals between the particles.particles.

↓↓ So, the mechanical strength of the mass is ↑ed.So, the mechanical strength of the mass is ↑ed.

The term mechanical interlocking is used The term mechanical interlocking is used to describe the hooking and twisting to describe the hooking and twisting together of the packed materials. together of the packed materials.

It has been claimed that materials bonding It has been claimed that materials bonding predominantly by this mechanisms require predominantly by this mechanisms require high compression forces and have an high compression forces and have an extremely long disintegration time.extremely long disintegration time.

It is dependent on the shape and surface It is dependent on the shape and surface structure of the particles.structure of the particles.

Role of moisture in tablet preparation:Role of moisture in tablet preparation:

At least some moisture is present in all tablet At least some moisture is present in all tablet formulas, coming from the granulating formulas, coming from the granulating solution after drying out or adsorbed from the solution after drying out or adsorbed from the atmosphere. Granulations that are dry have atmosphere. Granulations that are dry have poor compressional properties. poor compressional properties.

Water or saturated solutions of the material Water or saturated solutions of the material may form a film that acts as lubricant which may form a film that acts as lubricant which removes particles friction. removes particles friction.

So due to the presence of moisture, it is easy So due to the presence of moisture, it is easy to compress the tablet granules and stronger to compress the tablet granules and stronger intact tablet is formed through various bond intact tablet is formed through various bond formation. And less force is required to eject formation. And less force is required to eject the tablet.the tablet.

Example:Example: Optimum moisture content of lactose is Optimum moisture content of lactose is

12%12% Optimum moisture content of Optimum moisture content of

phenacetin is 3%phenacetin is 3%

From graph we can say-From graph we can say- 0.02% moisture can affect the proportion of 0.02% moisture can affect the proportion of

applied pressure transmitted to lower punch, applied pressure transmitted to lower punch, where as –where as –

0.55% or 10 % moisture, the behavior is just 0.55% or 10 % moisture, the behavior is just opposite as that for full dry material.opposite as that for full dry material.

Role of moisture in granulation:Role of moisture in granulation: Moisture is also important in moist Moisture is also important in moist

granulation process. Optimum granulation process. Optimum moisture content is required for moisture content is required for maximum bonding. maximum bonding.

A. Pendular state:A. Pendular state: Powder particles are wetted during the Powder particles are wetted during the

initial stage of granulation.initial stage of granulation. Liquid films are formed on the powder Liquid films are formed on the powder

surface and combine to form discrete surface and combine to form discrete liquid bridge at point of contacts.liquid bridge at point of contacts.

The aggregation has – Dry surfaceThe aggregation has – Dry surface Low densityLow density Non-spherical (in use)Non-spherical (in use)

B. Funicular state:B. Funicular state: As liquid content increases, several As liquid content increases, several

bridges may coalesce to give stronger bridges may coalesce to give stronger bridge.bridge.

The aggregation has – Dry surfaceThe aggregation has – Dry surface Denser than ‘A’Denser than ‘A’ Non-spherical / (nearly spherical)Non-spherical / (nearly spherical)

C. Capillary state:C. Capillary state: As more liquid is added, void space As more liquid is added, void space

is eliminated and more stronger is eliminated and more stronger bridge is formed.bridge is formed.

The aggregation has – wetted The aggregation has – wetted surfacesurface

Denser than “B”Denser than “B” Nearly spherical.Nearly spherical.

D. Droplet state:D. Droplet state: Further addition of liquid causes droplet Further addition of liquid causes droplet

formation, where particles are still held formation, where particles are still held together by surface tensiontogether by surface tension

The aggregation has – more wetted The aggregation has – more wetted surface surface

Maximum densityMaximum density Maximum consistencyMaximum consistency Spherical.Spherical.

Description of compression process:Description of compression process:

The process of compression can be described in terms of The process of compression can be described in terms of the relative volume (ratio of the volume of compressed mass to the the relative volume (ratio of the volume of compressed mass to the volume of the mass of zero void) and applied pressure which is volume of the mass of zero void) and applied pressure which is given bellow.given bellow. ------ ------

appliedapplied pressurepressure A A HH GG

BB

CC FF

EEDD

AAEE

Relative volume →Relative volume → P →P → Fig:Fig: Events of tablet compression process in times of applied pressure Vs relative Events of tablet compression process in times of applied pressure Vs relative

volume.volume.

AEAE → transitional repacking stage, where → transitional repacking stage, where granules are packed in such a way that granules are packed in such a way that particles are immobile and no. of inter particles are immobile and no. of inter granular points of contact is ↑ed and relative granular points of contact is ↑ed and relative volume is ↓ed.volume is ↓ed.

EFEF → with further increase in pressure, → with further increase in pressure, particles become close contact and particles become close contact and deformation at points of contact occurs.deformation at points of contact occurs.

FGFG → fragmentation and/ or plastic → fragmentation and/ or plastic deformationdeformation

GH GH → at some higher pressure, bonding and → at some higher pressure, bonding and consolidation of the solid occur to some consolidation of the solid occur to some extent and relative volume is decreased.extent and relative volume is decreased.

Heckel equation:Heckel equation:

For compressional process, “Heckel” proposed an For compressional process, “Heckel” proposed an equation based on 1st–order reaction-equation based on 1st–order reaction-

V V○V V○ Lu —— = Kp + ————Lu —— = Kp + ———— V-V∞ V○-V∞V-V∞ V○-V∞ Where,Where, V = Volume of pressure P.V = Volume of pressure P. V∞ = Volume of the solid. V∞ = Volume of the solid. K = Constant related to yield value (Heckel K = Constant related to yield value (Heckel

constant).constant). P = Pressure (applied).P = Pressure (applied). V○ = Original volume of powder including vo V○ = Original volume of powder including vo

Porosity and Pressure functionPorosity and Pressure function

Porosity is a function of the void in a powder Porosity is a function of the void in a powder column, and in general represent all pore column, and in general represent all pore space is considered, including both inter- space is considered, including both inter- and intraparticulate voids.and intraparticulate voids.

For porosity measurement, the dimensions For porosity measurement, the dimensions and weight of a powder column (i.e.apparent and weight of a powder column (i.e.apparent density) and the particle density (referred to density) and the particle density (referred to often as true density) of the solid materials often as true density) of the solid materials should be known. The porosity, ε can be should be known. The porosity, ε can be expressed by the equation expressed by the equation

ε = 1 – ρA / ρrε = 1 – ρA / ρr

Where, ρA, is the apparent density of a Where, ρA, is the apparent density of a powder column and ρpowder column and ρrr is the particle is the particle density of the compressed material. density of the compressed material. The value of ρA / ρr, also referred as The value of ρA / ρr, also referred as D, is regarded as the relative density or D, is regarded as the relative density or the packing fraction, which describes the packing fraction, which describes the solid fraction of a porous powder the solid fraction of a porous powder column.column.

Porosity and Pressure EquationsPorosity and Pressure Equations

Three equations describing the change Three equations describing the change of relative density in a powder column of relative density in a powder column as a function of the applied pressure as a function of the applied pressure have been widely applied to have been widely applied to pharmaceutical purposes, namelypharmaceutical purposes, namely

a. Heckel Equation (also called as a. Heckel Equation (also called as Athy-Heckell), Athy-Heckell),

b. Kawakita and b. Kawakita and c. Cooper – Eatonc. Cooper – Eaton

A. Heckel equation.A. Heckel equation.

Heckel introduced an equation for the Heckel introduced an equation for the densification phenomenon following the densification phenomenon following the first-order kinetics. The equation is first-order kinetics. The equation is

Ln 1 / 1-D = k P + A (1)Ln 1 / 1-D = k P + A (1) Where k, and A are constants obtained from Where k, and A are constants obtained from

the slope and intercept of the plot ln (1 / ( 1 the slope and intercept of the plot ln (1 / ( 1 – D)) versus P, respectively, D is the relative – D)) versus P, respectively, D is the relative density of a powder column at the pressure density of a powder column at the pressure P. P.

AA is an intercept which is extrapolated is an intercept which is extrapolated from the linear part of the Heckel plot. As from the linear part of the Heckel plot. As the plots were curved at low pressures,the plots were curved at low pressures,

Heckel related the constant Heckel related the constant AA to process to process of volume reduction which have taken of volume reduction which have taken place by (1) die filling and (2) particle place by (1) die filling and (2) particle rearrangement before deformation and rearrangement before deformation and bonding of the discrete particles, (2) bonding of the discrete particles, (2)

Densification of a powder by die Densification of a powder by die filling can be expressed as filling can be expressed as

ln 1 / 1-D0ln 1 / 1-D0 Where D0 is the relative density of a Where D0 is the relative density of a

powder column at resting pressure, powder column at resting pressure, and usually derived from the bulk and usually derived from the bulk density. density.

The combined effect of die filling and The combined effect of die filling and particle rearrangement at low pressures particle rearrangement at low pressures can be described by the equationcan be described by the equation

A = ln 1 / 1 – D0 + BA = ln 1 / 1 – D0 + B Where B describes a volume reduction Where B describes a volume reduction

purely by particle rearrangement. purely by particle rearrangement. Relative densities corresponding the Relative densities corresponding the

processes above are DA, which processes above are DA, which includes both die filling and particle includes both die filling and particle rearrangement, and DB, which rearrangement, and DB, which describes only the extent of particle describes only the extent of particle rearrangementrearrangement

In his original work Heckel studied In his original work Heckel studied the densification o metal powder . the densification o metal powder .

The slope k, of the Heckel plot was The slope k, of the Heckel plot was intended to give a measure of the intended to give a measure of the plasticity of a compressed material. plasticity of a compressed material.

Consequently , greater slopes Consequently , greater slopes indicated a greater degree of indicated a greater degree of plasticity of materialplasticity of material

Significance of Heckel equation / plotsSignificance of Heckel equation / plots 11. . Three types of volumes reduction mechanisms Three types of volumes reduction mechanisms

of pharmaceutical powders have been of pharmaceutical powders have been distinguished by using the Heckel equation. The distinguished by using the Heckel equation. The types are referred as A, B, and C (Fig 2)types are referred as A, B, and C (Fig 2)

In type A, size fractions had different initial packing In type A, size fractions had different initial packing fraction and the plot remained parallel as the fraction and the plot remained parallel as the compression pressure was increased.compression pressure was increased.

In type B, the plot were sightly curved at the initial In type B, the plot were sightly curved at the initial stages of compaction and later became stages of compaction and later became coincidental.coincidental.

In type C, the plot had an initial steep linear part In type C, the plot had an initial steep linear part after which they became coincidental with only after which they became coincidental with only trivial volume reduction.trivial volume reduction.

Generally type A, behavior was related Generally type A, behavior was related to the densification by plastic flow, to the densification by plastic flow, preceded by particle rearrangement.preceded by particle rearrangement.

In type B, powder densification occurs In type B, powder densification occurs by fragmentation of the particlesby fragmentation of the particles

Type C densification occurs by plastic Type C densification occurs by plastic flow but no initial particle flow but no initial particle rearrangement is observed.rearrangement is observed.

2. The crushing strength of tablet is related 2. The crushing strength of tablet is related to the value of K. Larger value of K to the value of K. Larger value of K indicates harder tablets. So this relation can indicates harder tablets. So this relation can be used in binder selection for tablet be used in binder selection for tablet formationformation

Hardness ∞K∞ Crushing strength.Hardness ∞K∞ Crushing strength. 3. Larger value of Heckel constant (K) 3. Larger value of Heckel constant (K)

indicates the one set of plastic deformation indicates the one set of plastic deformation of low pressure. of low pressure.

Plastic deformation ∞ KPlastic deformation ∞ K