Compression and compaction

process
and Pharmaceutical Industry

Dr. HMAJ Halahakoon MSc; PhD (Pharmaceutical Science)

Solid dosage forms, such as tablets and capsules, still constitute the most
widespread form of drug products due to their ease of use and the associated
high patient compliance.
PHARMACEUTICAL manufacturing companies that work with solid dosage
forms are facing a myriad of challenges.
Solid dosage forms must keep pace with other advancements in the pharma
industry and evolve and embrace technology and new materials in order to
retain their position in the market.
Oral solid dose formulations are efficient and cost-effective to manufacture,
shelf stable and easy to administer. Perhaps most importantly, they are
understood and accepted by patients worldwide.
 Oral solid dose products accounted for 31, or 53 percent, of the new drugs
approved by the FDA in 2018. This percentage of OSD approvals is higher than
previous years (50 percent in 2017 and 32 percent in 2016).
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 Future Market Insights projects the global OSD pharmaceutical formulation
market to grow 6.5 percent CAGR from 2017 to 2027.
 In terms of revenue, the market is projected to jump from $500,000 million
in 2017 to over $900,000 million in 2027.
 Opportunity for solid dose forms is being driven by new drug formulations.
Recent research has focused on controlled drug delivery, which offers
definite advantages over a conventional release formulation of the same
drug.
 Controlled release versions of solid dose drugs can reduce the dose frequency
and provide more uniform drug delivery.
 This can ensure safety and improve the efficacy of drugs, as well as increase
patient compliance. New formats for OSD drugs, such as bi-layer tablets,
minitablets, have become increasingly popular, enabling controlled delivery
of different drugs with pre-defined release profiles.
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Tableting is the compaction of powders into a single unit
and it is one of the most important unit operations in
the manufacturing of solid pharmaceutical dosage
forms, as the overwhelming majority of solid dosage
forms are tables.

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 Bachelor of Pharmacy program
Third-year B Pharm program
PM 3125:Pharmaceutical Technology I
Compression and compaction of
powder solids
Lecture Part I
Physical properties and parameters of the
Powders

Dr. HMAJ Halahakoon MSc; PhD (Pharmaceutical Science)

 “ The first information known to science about the use solid
compressed dosage forms for dosing the active substances by mankind
is presented in the Ebres Papyrus* (circa 1550 BC), which describes a
method for the manufacture of the pills.”
*The Ebers Papyrus, also known as Papyrus Ebers, is an Egyptian medical papyrus of herbal knowledge dating to circa 1550 BC. Among
the oldest and most important medical papyri of ancient Egypt 7
 Introduction to Topic
• Powders consist of solid particles surrounded by spaces
filled with fluid (typically air) and uniquely possess some
properties of solids, liquids, and gases.
• Powdered solids are heterogeneous.
• They are composed of individual particles of widely differing
sizes and shapes, randomly interspersed with air spaces.
• In the Pharmaceutical industry Powders properties
characterized under two levels, namely those associated
with an individual particle and those typical of bulk powder.
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 What are Pharmaceutical powders?
A Pharmaceutical powder is defined;
 as a dry, solid substance, composed of finely divided drugs
with or without excipients and intended for internal or
external use.
 It is a solid substance in finely divided state typically
obtained by crushing, grinding, or comminuting.
• Properly prepared, powders have a uniform, small particle
size (varying 10nm-1000μm) that has an elegant
appearance.
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 What are Pharmaceutical powders?
Classification of Powders
Powders can be broadly classified by the way they are
presented/dispensed to the user into bulk powders and divided
powders.
Other classifications of powders are based on particle size and
based on use.
Classification of powders based on dispensing;
1. Bulk powders
2. Divided powders
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 Bulk powders
 Bulk powders are dry, free-flowing preparations consisting of one
or a mixture of finely powdered substances and intended for
internal application (e.g., bulk powders for internal use) or external
application (e.g., bulk powders for external use).
 They are supplied in bulk or large quantities and are used for less
potent drugs.
 Bulk powders are dosed with acceptable accuracy and safety using
measuring devices such as the teaspoon, cup, or insufflator.
 This practically limits the use of orally administered bulk powders
to antacids, dietary supplements, laxatives, and a few analgesics.
 Many bulk powders are used topically.
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 Divided powders
Divided powders, or chartulae, are powders in which the individual
dose has been packed separately.
The traditional packing of divided powders is in wrapped paper.
Volatile or hygroscopic drugs are wrapped in aluminium foil or
plastic bags.
Divided powders used for potent drugs (drugs that are effective in
low concentrations), it was used before in old days but after
development of other dosage forms it became obsolete.
They are intended for internal use only.

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 Classification of powders based on particle size
 After preparation powders are classified according to their particle size. In order to
qualify the particle size of a given powder, the USP uses the following descriptive
terms:
a. Very coarse (No. 8) powder: All particles pass through a No. 8 sieve (2.38 mm)
and not more than 20% pass through a No. 60 sieve.
b. Coarse (No. 20) powder: All particles pass through a No. 20 sieve (0.84 mm)
and not more than 40% pass through a No. 60 sieve.
c. Moderately coarse (No. 40) powder: All particles pass through a No. 40 sieve
(0.42 mm) and not more than 40 % pass through a No. 80 sieve.
d. Fine (No. 60) powder: All particles pass through a No. 60 sieve (0.25 mm) and
not more than 40% pass through a No. 100 sieve.
e. Very fine (No. 80) powder: All particles pass through a No. 80 sieve (0.18 mm).
There is no limit to greater fineness.
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The behavior of powder can be studied under two
categories of its properties :
 1st level, the particle shape and size distribution.
 Secondary, flow and deformation.

Powder technology is concerned with solid/fluid

interactions, interparticle contact, and cohesion between
particles.

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Compaction of powders is the general term used
to describe the situation in which these materials
are subjected to some level of mechanical force.

Compaction
•Can be define as - compression and
consolidation of a two-phase (particulate solid-
gas) system due to the applied force.

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Compression
•A reduction in the bulk volume(Vb) of the
material as a result of displacement of the
gaseous phase.
Consolidation
• is an increase in the mechanical strength of the
material resulting from particle/ particle
interactions.

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 THE SOLID-AIR INTERFACE OF POWDER
• Atoms or ions located at the surface of any solid particle are
exposed to a different distribution of intramolecular and
intermolecular bonding forces than those within the
particle.
• The free surface energy of the solid, which plays a major
role in the interaction between particles, and between a
particle and its environment.
• Many important phenomena such as adsorption, cohesion
and adhesion are manifestations of this fundamental
property of all solids.
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The free surface energy of the solid
• Term surface free energy describes the excess energy that the
surface has compared to the bulk of the material.
• At the bulk, the molecules have similar molecules on their sides and
are pulled equally to all directions.
• This causes a zero-net force on the molecule. However, at the air –
solid interface, the molecules have similar neighbouring molecules
only on their side and below.
• The magnitude of the surface free energy depends on the
interaction between the molecules.

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The free surface energy of the solid
• The most commonly used surface free energy theory, WORK(Owens,
Wendt, Rabel and Kaelble model), divides the surface into two
components:
polar and dispersive.
The dispersive interactions include van der Waals forces such as London
dispersive force, Debye inductive force, and Keesom orientational
force(The Keesom interactions are due to the dipole–dipole interaction
between two permanent dipoles on a surface).
Polar interactions are hydrogen bonding and dipole-dipole interactions.
• When the surface free energy of the solid is high, it is usually easily
wetted by any liquid.
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 THE SOLID-AIR INTERFACE OF POWDER

The unsatisfied bonding forces at the surface of particles,

those that approach each other closely enough are
inherently attracted and tend to stick to one another. This
attraction between like particles is called cohesion.
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 THE SOLID-AIR INTERFACE OF POWDER

When those particles approach other types of particles or solid

surfaces, they are attracted to them, and this phenomena
termed as adhesion.
These attractions give rise to an intrinsic property of all bulk
powdered solids. (In materials science, an intrinsic property is independent
of how much of a material is present and is independent of the form of the
material) 21
- Adhesion of the unlike particles generates the resistance to
differential movement of their constituent particles when
subjected to external forces.
- The overall resistance to relative movement of particles
may be markedly affected by electrostatic forces and the
presence of an adsorbed layer of moisture on the particles.
• Many powders of pharmaceutical interest readily
develop electrostatic forces, especially when subjected
to internal friction.
• The electrostatics forces are relatively small, but
significant because they act over the distance than the
molecular forces do.
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Sintering is the process of
compacting and forming a
solid mass of material by
heat or pressure without
melting it to the point of
liquefaction.

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 THE SOLID-AIR INTERFACE OF POWDER
Adsorbed layer of moisture reduces the
chance of any complicating electrostatic
effect by providing a conducting path for
charge dissipation.
• These films of moisture can form liquid
bridges.
• Which hold the particles together by
surface tension effects and by negative
capillary pressure.
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 THE SOLID-AIR INTERFACE OF POWDER
Depending on the intensity of the mechanical treatment
and on the special properties of the powder bed, the
resulting irreversible deformations can be classified into
three groups:
Preserving the coherency of the solid phase in its
totality.
A second possibility is the fracture of the powder bed
into two or more parts.
The system has lost the typical properties of a powder
and represents an aerosol.
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 COMPRESSION OF A POWDER BED
Compression of a powder bed with partial elimination
of the gas phase enhances the enlargement of the
interparticular contact areas and thus the strength of
the powder bed, which may finally be transformed in
this way to a solid body (e.g., a tablet).

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 The inter-particular forces
The interparticular forces are roughly classified
according to their origin as:
• Electrostatic interactions
• Molecular interactions
Electrostatic interactions between molecules are
responsible for the formation of liquid and solid phases,
friction and lubrication, adhesion and wetting
phenomena, molecular self-assembly, biological
membranes, protein folding, and life itself.
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 Electrostatic Interactions
The electrostatic interactions between powder particles can be
describe using Coulomb’s Law.

F12 =
where is the permittivity constant 28
 TRIBOELECTROSTATIC CHARGE
•A turbulent movement of a powder causes very
frequent collisions of the particles.
• During each collision normally an interfacial
charge transfers occurs.
•the intensive movement of the material causing
the charge transfer, and this event called as a
triboelectrostatic charge transfer.

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TRIBOELECTROSTATIC CHARGE

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 TRIBOELECTROSTATIC CHARGE
• Particles with highly polar surfaces have, under normal conditions,
a water sorption layer which is able to distribute the transferred
charge over the surface.
• The thicker this layer, the higher is its conductivity and the more
easily is this charge distribution effected on the surface.
• The distribution becomes relatively homogeneous on the surface
of an amorphous spherical particle.
• But in the case of crystalline non-spherical particles, especially of
milled crystals with pointed edges, extremely high values of charge
will be concentrated in the tops of the edges.

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 TRIBOELECTROSTATIC CHARGE

Charge distribution under the influence of conductivity in the surface,

a) Amorph spherical particle, b) milled crystal.
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 The GranuCharge
instrument precisely
and automatically
determines the quantity
of electrostatic charges
that are generated
within a powder during
a flow in contact with a
chosen material.

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Depending on the composition of the powder
mixture and the intensity of the movement, one
can observe an increase in the bulk density and a
decrease of the flowability as a result of the two
materials attract each other because of their
opposite polarities.

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 Permanent Electrostatic Charge
• The permanent electrostatic charge occurs as a
consequence of the surface structure of the powder.
• Unlike amorphous materials, the surface of a
crystalline material is not uniform.

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 Permanent Electrostatic Charge
• Each face cuts the crystallographic lattice of the particle and
represents a special case of a crystallographic plan of the
lattice.
• The face, consequently, has its own structure, depending to
its orientation against the lattice.
• It contains only some special atoms or atomic groups of the
material in a state of order.
• each face has its own energy level, its own surface or
interface tension, and, with the presence of polar functional
groups, its own polarity.
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 Permanent Electrostatic Charge
• Due to the special chemical and crystallographic state of the
surface of solid particles, surfaces can be charged, even if
each particle in total is neutral.
• Amorphous materials also may have uniform charged ions in
their surface which are responsible for electrostatic
attractions or repulsions.
• A crystalline material with highly ordered functional polar
groups can also be the reason for a permanent charge on the
surface.

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 MOLECULAR INTERACTIONS
• Highly charged particles and faces give interactions over long
distances. The molecular interactions are also of an
electrostatic nature, but they have only a very limited range.
• They are secondary bonds or van der Waals attractions that
can be classified as ion-dipole, dipole-dipole, or van der
Waals-London interactions.

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 Capillary Forces
• A wetted powder contains, in addition to the sorption water, water
as a separate phase, with the typical properties of a liquid. If the
angle of contact between the water and the surface is small, a
limited amount of water takes a preferred place in the
interparticular contact regions with the formation of a meniscus
corresponding to Figure.

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 Capillary Forces
ΔP = 2 /r
where ΔP is the pressure difference, a is the
surface tension of the liquid phase, and r is the
radius of the concave deformation.

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 POWDER PROPERTIES
• In powder technology the interparticular interactions are
important for the flow properties and bulk density of a
powder, the mixing behavior, granulating, and tableting or
capsule filling.
• Interparticulate attraction in any case makes the flow
properties worse. On the other hand, electrostatic
repulsions may facilitate the flow of a powder bed.
• Despite this, triboelectrostatic charges should be avoided,
especially for powders provided for direct compression to
tablets or for capsule filling. 41
 POWDER PROPERTIES
• Flow properties themselves are influenced by the powder
properties and the interaction between the smallest
powder units, the particles.
• While flow properties are independent of the equipment
in which they were determined, the term “flowability”
always has to be connected with equipment and the way
in which it was tested.

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 Schematic visualization of the connection between the terms
“flowability” and “flow properties” and respective parameters

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 POWDER PROPERTIES
The following relations between powder properties and
flowability are of general nature:

• Flowability increases with decreasing width of the PSD .

• Flowability generally improves with coarser particles.
• Flowability decreases with increasing moisture content
until saturation with liquid.

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• The bulk density of powders is very sensitive to
electrostatic charge.
• The triboelectrostatic charge is not reproducible, does not
distribute homogeneously within a batch of a powder, and
changes rapidly during storage and the operation of tablet
compression.
• Because of this the triboelectrostatic charge influences in a
negative way the uniformity of the bulk density and with
this the uniformity of dosage.

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There are various ways to diminish the triboelectrostatic
charge transfer or to discharge the material.
The powder should have a sufficiently polar surface and a
water sorption layer.
The polarity of the surface can be enhanced by small
concentrations of excipients (e.g., Aerosil).
Triboelectrostatic charged materials can be discharged by
treatment with ionized air.
All charges discussed, which are located in the particle
surface independent of their nature—can be compensated by
the addition of amphiphilic excipients(e.g. Gelucire® 44/14 ).
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• These considerations show that the normally used
excipients in powder technology (e.g., lubricants) diminish
the negative influence of the charges.
• But they demonstrate also that after the treatment of a
powder with these excipients, intensive powder movements
must be avoided.
• For the influence of interparticular attraction on the
fluidization of a powder bed.
• Powder flowability is one of the key parameters in the
pharmaceutical tabletting process. The flowability is
affected by both the particles' properties and the tabletting
equipment characteristics
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• Physical properties of pharmaceutical solids predict the
performance and processing of solid dosage forms,
including their compressibility.
• In the pharmaceutical industry in particular, uniform flow
of solid mixtures is one of the most important
considerations in solid dosage manufacture.
• The uniform flow of the powder mixture is vital parameter
for the maintain consistency of the tablet weight with
minimum weight variation and the uniformity of the
content of the fabricating tablets.

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In the process of the direct compression of the solid dosage form used rotary
tablet machine with multi-station compression with gravity frame feeder or
forced feeder to fill the die cavity.
Through this process Powders can discharge from hoppers or storage bins in
one of two flow regimes:
• mass flow or funnel flow.

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 Powder Parameters
Flow property and compressibility of the powdered
materials used in the pharmaceutical industry can be
measured in terms of various parameters:
• Hausner’s ratio (HI),
• Carr’s index(CI),
• Angle of repose (α)
• Particle size.
• Tapped density (Dc) and Bulk density (Da) measurements
are also required to determine some of these
parameters.
*General Information / 1174 Powder Flow 891

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 Powder Parameters
ANGLE OF REPOSE (α)
• The angle of repose has been used in several branches of
science to characterize the flow properties of solids.
• Angle of repose is a characteristic related to
Interparticulate friction or resistance to movement
between particles.
• The angle of repose is the constant, three-dimensional
angle (relative to the horizontal base) assumed by a cone
like pile of material formed by any of several different
methods (USP or BP methods).
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 ANGLE OF REPOSE (α)
〈1174〉 Powder Flow / General Information

Table . Flow Properties and Corresponding

Angles of Repose

tan Ф =
Repose angle testing machine (Gardco)

There is two variation methods are described in the USP (1174

Powder flow) to determine the Angel of repose :
• Drained angle of repose
• Dynamic angle of repose 52
 Dynamic angle of repose determine method
• Dynamic angle method was most preferred since they closely
mimic the manufacturing situation in which the powder is in
motion.
• A typical dynamic test involves a hallow cylinder half filled with
the test powder, with one end sealed with transparent plate.
• The cylinder is rotated until the powder surface cascades.
• The curve wall is line with sand paper to prevent residential slip
at this surface.

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 FLOW RATES OF THE POWDER
• Alternatively, resistance to movement of particles,
especially for granular powders with little cohesiveness,
may be assessed by determining their flow rate Q through
a circular orifice (a tablet die, for instance) fitted in the base
of a cylindric container.
• Flow experiments with mixtures of different size fractions
of the same material can be particularly valuable, because
in many instances, there exist optimum proportions that
lead to a maximum flow rate.
• PSD is more important to evaluate the powder flowability.
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FLOW RATES OF THE POWDER
• Note that for this system, when the
proportion of fine particles exceeds
approximately 40%, there is a
dramatic fall in the flow rate.
• Particle size distribution is more
important to maintain the proper
flow rate of the powder mixture.
• It is well established that particle size
(mean and distribution) is one of the
most significant factors that affects
the flow behaviour of powders
Effect of fines on the rate of flaw of mixtures of coarse granules
(0.561 mm) as a function of increasing amounts of fines： (▲)
0.158 mm； (•) 0.09 mm; (★) 0.059 mm; (•) 0.048 mm. 56
• Small particles (<20 μm) have a relatively high
surface area to volume ratio, causing
interparticulate attractive forces to dominate
and resist bulk flow when a shear stress is
applied.
• Very fine particles possess attractive forces
such as Van Der Waals, electrostatics, surface
tension etc. and resulting cohesion of powder
and poor flow properties.
• As particle size increases, flow of the powders
also increases and after certain level works as
free flowing.
• Appropriate blend of coarse and fine particles
or in other words selection of particle size
distribution improves the flow properties. 57
• What is particle size distribution?
• Particle size distribution is a measurement that defines the number of
particles present according to their size.

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• In the pharmaceutical sector, it is the width of the distribution curve that is
of most importance.
• The key measurements that we use in setting up the Quadro Mills is to cite
three values—the D10, D50 and D90 as shown in Figure.
• The D50, the median, is defined as the particle size where half the
population lies below this value. Similarly, 90 percent of the population lies
below the D90 point, and 10 percent of the population lies below the D10.

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FLOW RATES OF THE POWDER

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 Compressibility index (CI)
• The compressibility index (CI) is a measure of the propensity of a
powder to consolidate and given by the equation：
CI =
where V - is the volume occupied by a sample of the powder after being
subjected to a standardized tapping procedure, and is the volume before
tapping.
Values of I below 15% usually give rise to good flow characteristics,
but readings above 25% indicate poor flowability.

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 Compressibility index (CI)

•Bulk density affects the value of the

compressibility index and factors such as
particle size and shape, surface area and
moisture content can influence its value, thus it
can be used as a way to assess these properties.

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