Solid state properties (Powder properties)

• Pharmaceutical powders are described as heterogeneous systems with different physical and/or
chemical compositions with a range of particle sizes between a few micrometers to about a
millimeter.

• At normal room temperature and pressure the majority of drugs and excipients exist as solids,
and so the study of solid state properties is of enormous pharmaceutical importance.

• On an average, more than 80% of its production is based on powders in tablet form

• Control of the powders physical behavior is crucial in the development and processing of solid
dosage forms.

• Key factor in a series of unit processes such as blending, compression, filling, transportation and
in scale-up operations

• In tablets compression and capsules filling, an optimal powder flow must be achieved in order to
produce final products with an acceptable uniformity content, weight variation and physical
consistence.
Solid state properties (Powder properties)

• Solid particles are made up of molecules that areheld in

close proximity to each other by intermolecular forces.
• The strength of interaction between two molecules is due
to the individual atoms within the molecular structure.
• For example, hydrogen bonds occur as a result of an
electrostatic attraction involving one hydrogen atom and
one electronegative atom, such as oxygen.
• For molecules that cannot hydrogen bond, attraction is
due to van der Waal's forces. dipole-dipole
(Keesom),dipole-induced dipole (Debye) and induced
dipole-induced dipole (London) forces.
Powder Flow properties
• To evaluate the powder flow properties, parameters such as -
Angle of repose, compressibility index or Carr’s index, and the
Hausner ratio, are generally employed.

• These methods are recommended by the pharmacopeia’s to

evaluate powders flowability

• They are easy to handle and their application is widely used in

industrial applications and in scale-up operations

• However, they are indirect methods and its relation with the
powders flow true behavior is not straightforward. Moreover

• To have a complete evaluation of the powders flowability, various

labor intensive and time-consuming techniques must be used
 Powder Rheology
• The study of the rheology of powders by the application of empirical
methods to analyze the torque and/or force encountered inside a powder
bed has been reported.

• For example in one study, the resistance to rotation of a propeller stirrer

used as a modified viscometer inside a predetermined quantity of a powder
bed has been described by Cole as a means to determine cohesivity of
powders used in capsule filling.

• Podczeck and Newton investigated the capsule-filling properties of

lubricated cellulose granules by the use of a powder rheometer and
concluded that it was possible to discern and identify suitable
concentrations of lubricant needed to augment the flowability of the fill
material.

• Freeman described several parameters that could serve as specific indices

of powder flowability derived from a series of experiments using a powder
rheometer.
Texture Analysis
• In one of the study study, a modified texture analyzer having a
rotating probe for torque measurements was used to study the flow
properties of drug powders’ granules before and after controlled
lubrication. Textural analysis is a technique that has found
widespread applications in pharmacy.

• The texture analyzer-powder rheometer assembly provides for the

detection of force and thereby torque by means of a sensitive
moving probe in a given sample of powder system

• The force detected versus the distance traveled by the probe,

rotating at a predetermined angle into the given powder bed, depicts
the work involved in getting the powder to flow around the geometry
of the probe.

• The integration of the area under the force-distance curve for each
particulate system based on the cohesivity or other properties can
be used for comparative analysis
Powder probe of the
texture analyzer and
the zoomed-in view of
the probe showing the
blade that describes a
true helix as it moves
through the powder bed
• The objective of this work was 2-fold: first, to understand and
evaluate the behavior of 3 different powders before and after
granulation and lubrication, and secondy to apply the proposed
method to determine lubrication efficiency of various powders.

The helical path taken by the probe inside the powder column is
shown in (a) and the end result after the probe retreats to its original
position is shown in (b).
• Powder flowability can be quantified from the curves by integrating
the area under the force-distance profiles, which will represent the
energy or work done by the blade to break the resistances to
movement of the blade within the powder bed for a given powder
sample (before and after lubrication)
• The applied test is capable of differentiating between properties of
cohesive, noncohesive, granulated, or plain powders
• Typical F-D profiles of plain powder, unlubricated granules and lubricated granules
of tetracycline showing reduction in AUC or work and smoothening of the profile.
Compactibility & Compression Properties of
Pharmaceutical Powders
• Compactibility is the ability of a powder bed to form a
mechanically strong tablet of specified strength
• Compressibility is the ability of a powder bed to be
compressed and consequently be reduced in volume.
• The characterisation of powder compression and
compaction plays an important role in the manufacturing
of tablets and granules, in the filling of hard-shell gelatin
capsules and in powder handling in general.
• Compaction consists of the simultaneous processes of
– compression
– consolidation of a two-phase (particulate solid-gas) system due
to an applied force.
• Compaction of powders is generally used to describe the
situation in which these materials are subjected to some
level of mechanical force.
Compression of Pharmaceutical Powders

• Complex and irreversible dynamic process

– Particle rearrangement and closer packing
– Elastic and plastic deformation
– Cold working, with or without fragmentation
• Powders intended for compression must
possess two essential properties:
– fluidity
– compressibility
Compression of Pharmaceutical Powders

• Powder fluidity
– required to transport the material
– provide adequate filling of the dies to produce
tablets of consistent weight and strength.
• Powder compression
– Depends on density and packing
characteristics of powder
 Stages involved in compression
• The only forces that exist between the particles are those that are
related to the packing characteristics of the particles, the density of
the particles and the total mass of the material that is filled into the
die
• External force - reduction in volume due to closer packing of the
powder particles- main mechanism of initial volume reduction
• As the load increases, rearrangement of particles becomes more
difficult and further compression leads to some type of particle
deformation
Types of Deformations
• Elastic deformation
– on removal of the load, the deformation is reversible -
it behaves like rubber
– All solids undergo elastic deformation when subjected
to external forces.
• Some materials, e.g. paracetamol, are elastic and
• There is very little permanent change (either plastic flow
or fragmentation) caused by compression:
• The material rebounds (recovers elastically)
• When the compression load is released. If bonding is
weak the compact will self-destruct and the top will
detach (capping)
• Else, whole cylinder cracks into horizontal layers
(lamination).
• Elastic materials require a particularly plastic tableting
matrix or wet massing to induce plasticity.
• Plastic deformation
– deformation not immediately reversible on the removal
of the applied force
– predominant in materials in which the shear strength is
less than the tensile or breaking strength
– believed to create the greatest number of clean
surfaces
– plastic deformation is a time dependent process
– Higher rate of force application leads to the formation of
less new clean surfaces - weaker tablets.
– Since tablet formation is dependent on the formation of
new clean surfaces, high concentration or over mixing
of materials that form weak bonds result in weak tablets
e.g. Mg stearate
Fragmenting Material

• Materials in which the shear strength is greater than the

tensile strength, particles may be preferentially fractured
• Smaller fragments then help to fill up the adjacent air
spaces.
• This is most likely to occur with hard, brittle particles and
is known as brittle fracture ; sucrose behaves in this
manner.
• The ability of a material to deform in a particular manner
depends on the lattice structure; in particular whether
weakly bonded lattice planes are inherently present.
• Brittle fracture creates clean surfaces that are brought in
intimate contact by applied load.
Types of Deformations
• Small particles may deform plastically through a process
known as microsquashing , and the proportion of fine
powders in a sample may therefore be significant.
• Highly irregular particles could also behave in this way;
hence particle shape is an important factor.
• In summary four stages of events are encountered
during compression
• (i) Initial repacking of particles.
• (ii) Elastic deformation of the particles until the elastic
limit (yield point) is reached.
• (iii) Plastic deformation and/or brittle fracture then
predominate until all the voids are virtually eliminated.
• (iv) Compression of the solid crystal lattice then occurs.
The deformation mechanisms of
powder particles under compression
Types of Deformations

• Tableted material should be plastic, i.e. capable of

permanent deformation
• Should also exhibit a degree of brittleness
(fragmentation).
• Thus if the drug dose is high and it behaves plastically,
the chosen excipients should fragment, e.g. lactose,
calcium phosphate.
• If the drug is brittle or elastic, the excipients should be
plastic, i.e. microcrystalline cellulose, or plastic binders
should be used in wet massing.
• As the dose is reduced this becomes less important as
the diluent vehicle dominates compressibility.
Consolidation
• Defn.: increase in the mechanical strength of a
material as a result of particle/particle interactions
• Various Hypothesis –
– When the surfaces of two particles approach each
other closely enough (e.g. at a separation of less
than 50nm), their free surface energies result in a
strong attractive force through a process known as
cold welding .
– This hypothesis is favoured as a major reason for
the increasing mechanical strength of a bed of
powder when subjected to rising compressive
forces.
Consolidation (Hypothesis)
• Any applied load to the bed is transmitted
through particle contacts.
• Under appreciable forces, this transmission may
result in the generation of considerable frictional
heat.
• If this heat is dissipated, the local rise in
temperature could be sufficient to cause melting
of the contact area of the particles
• When the melt solidifies, fusion bonding occurs,
which in turn results in an increase in the
mechanical strength of the mass.
Consolidation (Hypothesis)
• During compression, the powder compact
typically undergoes a temperature increase
usually between 4 and 30 o C
• Depends on
– friction effects
– Material characteristics,
– lubrication efficiency
– magnitude and rate of application of compression
forces
– machine speed
• As the tablet temperature rises, stress relaxation
and plasticity increases while elasticity
decreases and strong compacts are formed
Compression events
• Consolidation time: time to reach
maximum force.
• Dwell time: time at maximum force.
• Contact time: time for compression and
decompression excluding ejection time.
• Ejection time: time during which ejection
occurs.
• Residence time: time during which the
formed compact is within the die.
Decompression
• Compression process is followed by a decompression
stage, as the applied load is removed.
• The rate at which load is applied and removed may be a
critical factor in materials for which dependence on time
is significant.
• If a plastically deforming solid is loaded (or unloaded)
too rapidly for the process to take place, the solid may
exhibit brittle fracture.
• Research investigations in recent years have shifted to
relating the capping and lamination tendencies of tablet
formulations to their plastic and elastic behaviour during
the compression/ decompression/ ejection cycle
Decompression
• 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 tablet must be

mechanically strong enough to withstand these new stresses,
otherwise structural failure will occur.

• In particular, the degree and rate of stress relaxation within

tablets, immediately after the point of maximum compression
have been shown to be characteristic of a particular system

• This phase of the cycle can provide valuable insight into the
reasons behind inferior tablet quality and may suggest a
remedy.
Force transmission through a powder bed
 Force transmission through a powder bed
(SINGLE STATION)

• During normal tablet operations, consolidation is

accentuated in those regions adjacent to the die
wall
• Material is subjected to intense shear as it is
compressed axially and pushed along the wall
surface.
• The applied force is not transmitted uniformly
throughout the entire mass because of
cohesiveness of powder
• The force exerted by the upper punch
diminishes exponentially at increasing depths
below it
The distribution of force in an
isolated punch and die set
• The relationship between upper punch force, F A , and lower punch
force, F L , may be expressed in the form:
                    F L    =   F A   .   ekH/D                                               
• where k is an experimentally determined material-dependent
constant that includes a term for the average die-wall frictional
component. 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.
• The effect of die wall friction can be reduced by having smaller
tablet-to-diameter ratios and by adding lubricants
 Force transmission through a powder bed

• Since there must be an axial (vertical) balance of forces:

                            F A    =   F L   +  F D                                             
where F A is the force applied to the upper punch, F L is that proportion of it
transmitted to the lower punch, and F D is the reaction of the die wall due to the
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, F
M , has been proposed, where:

•                             F M    =   (F A   +  F L )  /  2                                      

• F M offers a practical friction-independent measure of compaction load, which is
generally more relevant than F A
• In single-station presses, where the applied force transmission decays
exponentially as in equation a more appropriate geometric mean force, F G ,
might be:
                         F G     =    ( F A   .   F L ) 0.5                                      
Force transmission - Poisson ratio
• As the compressional force is increased and the
repacking of the tabletting mass is completed, the
material may be regarded as a single solid body.
• When, the compressive force applied in one direction
(e.g. vertical) results in a decrease, DH, in the height, i.e.
a compressive stress.
• In the case of an unconfined solid body, this would be
accompanied by an expansion in the horizontal direction
of DD.
• The ratio of these two dimensional changes are known
as the Poisson ratio (l) of the material, defined as:
l     =   D D   /   D H                                                
• The Poisson ratio is a characteristic constant for each solid material
and may influence the tabletting processes.
• 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 F R develops perpendicularly to
the die-wall surface
• Materials with larger Poisson ratios giving rise to higher values of FR
• Classical friction theory can be applied to deduce that the axial
frictional force F D is related to F R by the expression:
                    F D     =    m W   .  FR                                             
•  m W is the coefficient of die-wall friction.  F R is reduced when
materials of small Poisson ratios are used, and in such cases, axial
force transmission is optimum.
• The frictional effects represented by  m W arise from the
shearing of adhesions that occurs as the particles slide
along the die-wall.
• Hence, its magnitude is related to the shear strength, S,
of the particles (or the die-wall-particle adhesions if these
are weaker) and the total effective area of contact, A e ,
between the two surfaces.
• Optimal force transmission is also realized when F D
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 A e ).
Compaction data analysis
• The parameters monitored during compaction vary widely in these
studies.
• Various parameters have been used to assess the compaction
behavior of a variety of pharmaceutical powders and formulations
– Forces on the punches
– displacement of the upper and lower punches,
– axial to radial load transmission,
– die wall friction,
– ejection force,
– temperature changes
• Resulting data may be expressed equivalently in term of stress-
strain, pressure-volume or pressure –density since the natural
strain, for example, is equal to the natural log of the ratio of the initial
bed height or volume to the current height or volume respectively
Compaction data analysis
• A compaction equation relates some measure of the state of consolidation
of a powder, such as porosity, volume (or relative volume), density or void
ratio, with a function of the compaction pressure.
• Many compaction equations have been proposed and today, more than
fifteen different mathematical descriptions of the compaction process have
been compiled in the literature including those of Heckel , Kawakita and
Adams which have been validated for pharmaceutical systems.
• However, it is highly unlikely that a single compaction equation will fit all
the compaction mechanisms.
• In interpreting compaction curves, it is therefore essential to know which
mechanisms are operating, or not, over different region of pressure.
• A good compaction curve should be able to indicate changes in the
compression mechanism.
The ideal requirements for a compression /
compaction equation
• The model should cover the whole range of densification with sufficient
accuracy.
• The parameters should be related to physical relevent properties of the
powder.
• The parameters should be sensitive to changes in formulation and
experimental variables and insensitive or at least proportional to minor
changes in normalisation factors like density or initial volume.
• The model and its parameters should be easily estimated by general
available computer programs.
• The model should significantly differentiate between powders and
dissimilar compression characteristics.
• The quality of the model should be evaluated by a combination of the
range of densification covered and the goodness-of-fit to the observed
data.
Heckel equation
• Powder packing with increasing compression load is
normally attributed to particle rearrangement, elastic and
plastic deformation and particle fragmentation
• The Heckel analysis is a popular method of determining the
volume reduction mechanism under the compression force
• Based on the assumption that powder compression follows
first order kinetics with the interparticulate pores as the
reactants and the densification of the powder as the product.
• According to the analysis, the degree of compact
densification with increasing compression pressure is
directly proportional to the porosity as follows:
•                             dρ R / dP    =    k E    
Heckel equation
• where ρ R is the relative density at pressure, P, and E is the porosity.
• The relative density is defined as the ratio of the density of the
compact at pressure, P, to the density of the compact at zero void or
true density of the material
• The porosity can also be defined as:
•                             E   =   (V p   -  V)  /  V p    =  1  -  ρ R                
• where V p and V are the volume at any applied load and the volume at
theoretical zero porosity, respectively.
• Thus, equation dρ R / dP    =    k E  can be expressed as:
•                             dρ R / dP   =   k  ( 1  -  ρ R )                            
• and then transformed to:  
In [1  /  (1 - ρ R )]   =   kP  +  A   ie  (y = mx +c)
• Plotting the value of In [ 1 / (1 - ρ R )] against applied pressure, P,
yields a linear graph having slope, k and intercept, A.                         
Heckel equation
• The reciprocal of k yields a material-dependent constant
known as yield pressure , P y which is inversely related to
the ability of the material to deform plastically under
pressure.
• Low valuesof Pyindicate a faster onset of plastic
deformation
• This analysis has been extensively applied to
pharmaceutical powders for both single and multi-
component systems
• The intercept of the extrapolated linear region, A, is a
function of the original compact volume
Heckel equation
• From the value of A, the relative density, D A , which
represents the total degree of densification at zero and
low pressures can be calculated using the equation
                                 A     =   In  1  /  (1 - D A )  
D A    =   1   -   e - A
• The relative density of the powder bed at the point when
the applied pressure equals zero = D 0
• Describes the initial rearrangement phase of
densification as a result of die filling.
• D 0 is determined experimentally and is equal to the ratio
of bulk density at zero pressure to the true density of the
powder
• The loose packing of granules at zero pressure tends to
yield low D 0 values
Heckel equation
• The relative density, D B , describes the phase of
rearrangement of particles in the early stages of
compression
• Indicates the extent of particle or granule fragmentation,
• The extent of the rearrangement phase depends on the
theoretical point of densification at which deformation of
particles begins. D B can be obtained from the equation:
                 D B    =   D A   -  D 0  
Application of Heckel equation

• To distinguish between substances that consolidate by

fragmentation and those that consolidate by plastic
deformation.
• As a means of assessing plasticity.
– Materials that are comparatively soft readily undergo
plastic deformation.
– Conversely, materials with higher mean yield
pressure values usually undergo compression by
fragmentation first, to provide a denser packing.
– Hard, brittle materials are generally more difficult to
compress than soft ones.
• Based on Heckel eqn – 3 types of
powder-A, B, & C • With type A materials, a linear
relationship is observed, with the plots
remaining parallel as the applied
pressure is increased indicating
deformation apparently only by plastic
deformation

•An example of materials that exhibit

type A behavior is sodium chloride.

•Type A materials are usually

comparatively soft and readily
undergo plastic deformation retaining
different degrees of porosity
depending on the initial packing of the
powder in the die.

•This is in turn influenced by the size

distribution, shape, e. t. c., of the
In [1  /  (1 - ρ R )]   =   kP  +  A  original particles.
• For type B materials, there is
an initial curved region
followed by a straight line

• This indicates that the

particles are fragmenting at
the early stages of the
compression process

• Type B Heckel plots usually

occur with harder materials
with higher yield pressures
which usually undergo
compression by fragmentation
first, to provide a denser
packing. Lactose is a typical
example of such materials.
• For type C materials, there
is an initial steep linear
region which become
superimposed and flatten
out as the applied pressure
is increased
• York and Pilpel (43)
ascribed this behavior to
the absence of a
rearrangement stage and
densification is due to
plastic deformation and
asperity melting.
Application of Heckel equation

• The crushing strength of tablets can be correlated with

the values of k of the Heckel plot
• Larger k values usually indicate harder tablets.
• Such information can be used as a means of binder
selection when designing tablet formulations.
• Heckel plots can be influenced by the overall time of
compression, the degree of lubrication and even the size
of the die, so that the effects of these variables are also
important and should be taken into consideration.
Kawakita equation
• The Kawakita equation was developed to study powder
compression using the degree of volume reduction, C, a
parameter equivalent to the engineering strain of the
particle bed
•           C   =   (V 0   -  V p ) / V 0    =   a b P / (1+ bP)  
• can be rearranged to give:
•  P / C   =   P / a   +   1 / ab            
• where C is the degree of volume reduction,
• V 0 is the initial volume of the powder bed and
• V p is the powder volume after compression;
• a and b are constants which are obtained from the slope
and intercept of the P/C versus P plots                       
Kawakita equation
• The constant a is equal to the minimum porosity of the
bed prior to compression while b , which is termed the
coefficient of compression, is related to the plasticity of
the material.
• The reciprocal of b yields a pressure term, P k , which is
the pressure, required to reduce the powder bed by
50%
• The value of P k provides an inverse measurement of
plastic deformation during the compression process.
The lower the value of P k , the higher the degree of
plastic deformation occurring during compression
Kawakita equation (Application)
• Kawakita equation is best used for low pressures and
high porosities
• Kawakita relationship may be employed to determine
the tensile strength of agglomerates provided that the
influence of the friction at the die wall of the
compaction cell has been taken into account
• Equation holds best for soft fluffy pharmaceutical
powders and particular attention must be paid to the
measurement of the initial volume, Vo, and that
deviation from this equation is sometimes due to the
measured value of Vo.
• Both Heckel & Kawakita plots have their limitations and
are believed to generally exhibit linearity for materials at
high and low pressures, respectively
• Thus both plots are used with the hope of obtaining more
accurate information on the compressional
characteristics of the tablet formulations
• P y values relate essentially to the onset of plastic
deformation during compression while the P k values
appear to relate to the amount of plastic deformation
occurring during the compression
• It should be possible, therefore, to obtain more
information on the deformation profile of a material from
the combined use of P k and P y
• For example, to obtain optimum plasticity, there may
not be much point in using a long dwell time for a
material with a low P y but a high P k .
• On the other hand, it should be of significant benefit to
use a long dwell time for a material with a high P y but
low P k values.
• Material with low P y and P k values should not give any
appreciable problems on any type of tabletting
machine,
• Materials with a combination of high P k and P y values
would give compressional problems on virtually any
type of tabletting machine, and reformulation or the
addition of plastic materials may be necessary in such
cases.
• A material exhibiting crushing strengths in order B > A >
C would probably have plastic tendencies
• Increasing dwell time at compression (B) will increase
bonding
• If a material is predominantly fragmenting,
neitherlubricant mixing time (C) nor dwell time (B} should
affect tablet strength.
• Typically for materials that undergo plastic deformation, as
machine speed is increased there is less time for stress
relaxation.
• Under these conditions, the tablets may cap and laminate.
• However, capping and lamination can be eliminated or
minimized by
– slowing down the compression process (reducing the machine
speed),
– lowering the rate of force application (larger compression roller
diameter),
– increasing the time of compression (multistage
compression).
• Materials which show crushing strengths which are
independent of the method of manufacture are likely to
exhibit fragmenting properties during compression, with a
high friability
• The final tablet properties are also affected by the
consolidation (i.e., bonding) mechanisms of the powder which
is influenced by
– its chemical nature
– surface area of the contact points,
– Contamination (including film coatings such as
magnesium stearate),
– Interparticle distance.
Thus materials which show crushing strengths which are
independent of the method of manufacture outlined in are
likely to exhibit fragmenting properties during compression,
with a high friability.