Granulation

Technology
Mahbubul Karim
 Topics

Introduction to granulation
Characterization of granulation
Principle governing particle size
enlargement
Granule size enlargement and
interpretation of size data
Characterization of granule shape
friability
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 Topics

Characterization of granule surface area

Granule density and packing
characteristic
Electrostatic properties of tablets
Rheological properties of granules
Granule strength and friability

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Introduction to granulation and
granules
What is Granulation.
a size-enlargement process
during which small particles are formed
into larger,
physically strong agglomerates in which
the original particles can still be
indentified.

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 granulation and granules

In the granulation process the primary

powder particles are made to adhere to
form larger, multi particle entities called
granules.

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granulation and granules

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 Reasons for granulation

Improve the flow properties of the mix

Prevent segregation of the constituents of

the powder mix

Improve the compaction characteristics of

the mix

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 Reasons for granulation
Densify the powder mixture and reduce
dust

Control the rate of drug release

Improve the appearance of the tablet

Improve the dissolution characteristics of

the finished tablets.

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 Reasons for granulation

Facilitate metering or volume dispensing

Improve content uniformity

Decrease dust generation and reduce

employee exposure to drug product

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Characterization
of Granulation

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 PHYSICAL AND CHEMICAL
CHARACTERIZATION OF GRANULES

Dosage form performance highly depends on

the physical and chemical properties of the
granules. Most of the techniques used for
granulation characterization are conducted
during the research and development
stage of product development.

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 PHYSICAL AND CHEMICAL
CHARACTERIZATION OF GRANULES

Physical property characterization of pharmaceutical

granulation is important. Because
materials
intended for compaction into tablet must
possess two characteristics : fluidity and
compressibility. Tablet materials should
therefore be in physical form that flows smoothly
and uniformly. The ideal physical form for this
purpose is spheres, since these offer minimum
contact surfaces and improve flowability.

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 PHYSICAL AND CHEMICAL
CHARACTERIZATION OF GRANULES

Physical characterization (particle size and

shape, density, surface roughness, bulk
density etc) can be performed at
molecular, particulate, or bulk
(macroscopic) levels.
The flowability of a powder is affected by
physical properties of particles.

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 PHYSICAL AND CHEMICAL
CHARACTERIZATION OF GRANULES

Chemical properties are equally important

due to their impact on specifications of a
dosage form such as content uniformity,
chemical purity, and in vitro performance.
The effect of granule size on the
dissolution performance, could ultimately
affect the outcome of a bioequivalence
study.

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 Desirable Granule Properties

Controlled Size Distribution

Specific Granule Voidage-Intragranular
Porosity
Specific Bulk Density
Suitable Structural Stability and Physical
Strength

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 Monitor & Control
(What, When, How & Why)

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Principle governing
particle size
enlargement

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 Method of Granulation

Granulation methods can be divided

into two major types:
> wet methods which utilize some form of
liquid to bind the primary particles, and
> dry methods which do not utilize any
liquid.

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 Wet Granulation
(involving wet massing)
Wet granulation involves mix of dry
primary powder particles using a
granulating fluid. The fluid contains a
solvent which must be volatile so that it
can be removed by drying, and be non-
toxic. Typical liquids include water, ethanol
and isopropanol, either alone or in combination.

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 Wet Granulation
(involving wet massing) contd

The granulation liquid may be used

> alone or,
> as a solvent containing a dissolved
adhesive (also referred to as a binder or
binding agent)
which is used to ensure particle adhesion
once the granule is dry.

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 Wet Granulation
(involving wet massing) contd

Water is most commonly used for

economical and ecological reason.
It may adversely affect drug stability,
causing hydrolysis of susceptible products,
and it needs a longer drying time than do
organic solvents.

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 Wet Granulation
(involving wet massing) contd

This increases the length of the process

and may affect stability because of the
extended exposure to heat.
The primary advantage of water: it is non-
flammable, which means that expensive
safety precautions such as the use of
flameproof equipment need not be taken.

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 Wet Granulation
(involving wet massing) contd

Organic solvents are used

> when water-sensitive drugs are processed,
as an alternative to dry granulation, or
> when a rapid drying time is required.

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 Wet Granulation
(involving wet massing) contd

In the traditional wet granulation method

wet mass sieve wet granules
dried screening agglomerates of
initial particle aggregation.
Variations of this traditional method
depend on the equipment used, but the
general principle of initial particle
aggregation using a liquid remains
in all of the processes.
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 Wet Granulation
(involving wet massing) contd

Methods
> Low Shear Wet Granulation
> High Shear Wet Granulation
> Spray Granulation
> Melt Granulation and Pelletization:
Melt granulation and melt pelletization are agglomeration processes
that have gathered increasing interest in the pharmaceutical industry
for the concept of utilizing a molten liquid as a binder.

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 Dry Granulation
In dry methods of granulation the primary
powder particles are aggregated under high
pressure.
There are two main processes:
> Slugging, is produced in a heavy-duty
tabletting press (a process known as 'slugging') or
> Compaction, powder is squeezed between
two rollers to produce a sheet of material ('roller
compaction').

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 Dry Granulation contd

In both cases
these intermediate products are broken
using a suitable milling technique to
produce granular material, which is usually
sieved to separate the desired size
fraction.
The unused fine material may be reworked to
avoid waste.

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 Dry Granulation contd

Dry method may be used for drugs

that do not compress well after wet
granulation, or
those which are sensitive to moisture.

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GRANULATION MECHANISMS

Particle-bonding mechanisms
To form granules, bonds must be formed
between powder particles so that they
adhere to each other and these bonds
must be sufficiently strong to prevent
breakdown of the granule to powder in
subsequent handling operation..

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 GRANULATION MECHANISMS contd

There are five primary bonding mechanisms

between particles:
1. Adhesion and cohesion forces in the immobile
liquid films;
2. Interfacial forces in mobile liquid films within
the granules;
3. The formation of solid bridges after solvent
evaporation;
4. Attractive forces between solid particles;

5. Mechanical interlocking.
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 GRANULATION MECHANISMS contd

Different types of mechanism were identified in each

group and the ones discussed below are those that are
relevant to pharmaceutical granulations.
Adhesion and cohesion forces in immobile films
Interfacial forces in mobile liquid films
Solid bridges
Attractive forces between solid particles

Cohesion: Holding the particles of a homogeneous body

together; as, cohesive attraction; producing cohesion;
as, a cohesive force.

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 GRANULATION MECHANISMS contd

Adhesion and cohesion forces in immobile films

If sufficient liquid is present in a powder to form
a very thin, immobile layer, there will be an
effective decrease in interparticulate distance
and an increase in contact area between the
particles. The bond strength between the particles will
be increased because of this, as the van der Waals
forces of attraction are proportional to the particle
diameter and inversely proportional to the square of the
distance of separation.

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 GRANULATION MECHANISMS contd

Adhesion and cohesion forces in immobile films

In dry granulation, however, the pressures used
will increase the contact area between the
adsorption layers and decrease the
interparticulate distance, and this will contribute
to the final granule strength.

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 GRANULATION MECHANISMS contd

Adhesion and cohesion forces in immobile films

Thin, immobile layers may also be formed by
highly viscous solutions of adhesives,
and so the bond strength will be greater than that
produced by the mobile films.
The use of starch mucilage in pharmaceutical
granulations may produce this type of film.

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 GRANULATION MECHANISMS contd

Interfacial forces in mobile liquid films

During wet granulation, liquid is added to the powder mix
and is distributed as films around and between the
particles.
Sufficient liquid is usually added to produce a mobile
film.
There are three states of water distribution between
particles, which are illustrated in Figure 1.

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 GRANULATION MECHANISMS contd

Interfacial forces in mobile liquid films

Fig 1 : Water distribution between particles of a granule

during formation and drying.

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 GRANULATION MECHANISMS contd

Interfacial forces in mobile liquid films

These wet bridges are only temporary structures in wet granulation

because the moist granules will be dried.
They are, prerequisite for the formation of solid bridges formed by
adhesives present in the liquid, or by materials that dissolve in the
granulating liquid.

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 GRANULATION MECHANISMS contd
Interfacial forces in mobile liquid films
At low moisture levels, termed the pendular state, the
particles are held together by lens-shaped rings of
liquid.
When all the air has been displaced from between the
particles the capillary state is reached, and the
particles are held by capillary suction at the liquid/air
interface, which is now only at the granule surface.
The funicular state represents an intermediate stage
between the pendular and capillary states. Moist granule
tensile strength increases about three times between the
pendular and the capillary state.

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 GRANULATION MECHANISMS contd

Solid bridges
These can be formed by:
1. partial melting
2. hardening binders
3. crystallization of dissolved substances.

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 GRANULATION MECHANISMS contd

Solid bridges
1. Partial melting
Although not considered to be a predominant
mechanism in pharmaceutical materials, it is
possible that the pressures used in dry
granulation methods may cause melting of low
melting-point materials where the particles touch
and high pressures are developed. When the
pressure is relieved, crystallization will take
place and bind the particles together.

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 GRANULATION MECHANISMS contd

Solid bridges
2. Hardening binders
This is the common mechanism. An adhesive is
included in the granulating solvent.
The liquid will form liquid bridges, and the
adhesive will harden or crystallize on drying to
form solid bridges to bind the particles.
Adhesives such as PVP, the cellulose derivatives (such
as CMC) and pregelatinized starch function in this way.

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 GRANULATION MECHANISMS contd

Solid bridges
3. Crystallization of dissolved substances
The solvent used to mass the powder during wet
granulation may partially dissolve one of the powdered
ingredients.
When the granules are dried, crystallization of this
material will take place and the dissolved substance then
acts as a hardening binder.
Any material soluble in the granulating liquid will function
in this manner,e.g. lactose incorporated into dry
powders granulated with water.

The size of the crystals produced in the bridge will be

influenced by the rate Mahbubul
of drying
Karim of the granules: the 42
 GRANULATION MECHANISMS contd

Solid bridges
3. Crystallization of dissolved substances
The size of the crystals produced in the bridge will be
influenced by the rate of drying of the granules:
the slower the drying time, the larger the particle size.
It is important that the drug does not dissolve in the
granulating liquid and recrystallize, because it may
adversely affect the dissolution rate of the drug if crystals
larger than that of the starting material are produced.

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 GRANULATION MECHANISMS contd

Attractive forces between solid particles

In the absence of liquids and solid bridges
formed by binding agents, there are two types
of attractive force that can operate between
particles in pharmaceutical systems.

Electrostatic forces
Van der Waals forces

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 GRANULATION MECHANISMS contd

Attractive forces between solid particles

Electrostatic forces may be important in causing powder
cohesion and the initial formation of agglomerates, e.g. during
mixing. In general they do not contribute significantly to the
final strength of the granule.
Van der Waals forces, however, are about four orders of
magnitude greater than electrostatic forces and contribute
significantly to the strength of granules produced by dry
granulation. The magnitude of these forces will increase as
the distance between adjacent surfaces decreases, and in
dry granulation this is achieved by using pressure to force
the particles together.

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 Theory of granulation
The theory of granulation can be described in four
stages. These four states are termed:

1. Pendular
2. Funicular
3. Capillary, and
4. Droplet or Suspension State.

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Mechanisms of granule formation

The proposed granulation mechanism can

be divided into three stages.
1. Nucleation
2. Transition
3. Ball growth

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Mechanisms of granule formation
1. Nucleation
Granulation starts with particle-particle
contact and adhesion due to liquid
bridges. A number of particles will join to
form the pendular state illustrated in
Figure1. Further agitation densities the
pendular bodies to form the capillary state,
and these bodies act as nuclei for further
granule growth.

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Mechanisms of granule formation
2. Transition:
Nuclei can grow in two possible ways: either single particles can
be added to the nuclei by pendular bridges, or two or more nuclei
may combine. The combined nuclei will be reshaped by the
agitation of the bed.
This stage is characterized by the presence of a large number of
small granules with a fairly wide size distribution. If the size
distribution is not excessively large, this point represents a suitable
endpoint for granules used in capsule and tablet manufacture. as
relatively small granules will produce a uniform tablet die or capsule
fill. Larger granules may give rise to problems in small-diameter dies
owing to bridging across the die and uneven fill.

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Mechanisms of granule formation
3. Ball growth
Further granule growth produces large, spherical
granules and the mean particle size of the
granulating system will increase with time.
If agitation is continued, granule coalescence
will continue and produce an unusable,
overmassed system, although this is dependant
upon the amount of liquid added and the
properties of the material being granulated.

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Mechanisms of granule formation
The four possible mechanisms of ball growth
are illustrated in Figure 2.
1.Coalescence
Two or more granules join to form a larger
granule.
2.Breakage
Granules break into fragments which adhere
to other granules, forming a layer of material
over the surviving granule.
3. Abrasion transfer
Agitation of the granule bed leads to the
attrition of material from granules. This
abraded material adheres to other granules,
increasing their size.
4.Layering
When a second batch of powder mix is
added to a bed of granules the powder will
adhere to the granules, forming a layer over
the surface and increasing the granule size.

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Equipment
of Granulation

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 Equipments
Wet Granulation

Mixer Grinder Dryer

Dry Granulation

Mixer Grinder

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 Equipments
Title of Slide
High Speed Mixer
Wet Granulator
Paste Kettle
Fluid Bed Dryer
Dry Granulator
Final Blender

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 Equipments
Title of Slide
The equipments used during the
granulation processes are classified into
three major categories, based on the
shearing strength it generates on the
powder bed.

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 Equipments
Title of Slide
1. Low-shear granulatorstwin shell with an agitator
bar, dough mixer or planetary mixer, ribbon blenders,
and fluid bed granulator without the rotogranulator.

2. Medium-shear granulatorsfluid bed granulators

with a rotogranulator attachment.

3. High-shear granulators consist of a mixing bowl, a

three-bladed impeller, and an auxiliary chopper.

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 Low shear granulator
Fig 6 : Sigma blade mixer.

Fig 3 : Ribbon blender.

Fig 4 : Planetary mixer. Fig 5 : Orbiting screw mixer.

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 Low shear granulator

Fig 7 : Zig-Zag mixeragglomerator. (Courtesy of Patterson-Kelley Co., Division of

Harsco Corp., East Stroudsburg, PA.)

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Medium shear granulator
Title of Slide

Fig 8 : Fluidized bed granulator

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Medium shear granulator
Title of Slide

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Medium shear granulator
Title of Slide

Fig 10 : (A) Schematic of the overlap gill plategill

arrangements. (B) Container with the
overlap gill distributor. (Courtesy of Niro Pharma Systems.)

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 HighTitle
shear granulator
of Slide

Fig 12 (b) :Schematic view of top-driven vertical high

shear granulator. (ULTIMAGRALTM/
ULTIMAPROTM courtesy of Niro Pharma Systems.)
Fig 12 (a) Schematic view of a bottom-driven
vertical high shear granulator with horizontal
chopper shaft. (PMA through-the-wall courtesy of
Niro Pharma Systems.)

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HighTitle
shear granulator
of Slide

Fig 13 : (A) The top view of a bottom-driven

impeller with a horizontal chopper. (Courtesy of
Diosna.) (B) The top view of a bottom-driven
impeller with a horizontal chopper inside a conical
shaped mixing bowl. (Courtesy of Glatt Air
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 HighTitle
shear granulator
of Slide
Rapid Mixer Granulator is designed to achieve excellent mixing and
consistent granules at lower operating cost along with higher productivity.

Fig1 :Rapid Mixer Granulator Fig 2 :Rapid Mixer Granulator

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Granulation process parameters

Impeller Speed
Chopper Speed
Water Addition Rate and Method
Massing Time
Load of the Mixer

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Granulation process parameters

Impeller Speed
Higher Impeller speeds generally results in
denser and smaller granules. Low impeller
speeds generally result in more porous, large
granules.
Chopper Speed
Generally Chopper speed has no significant
effect on granule size and density but in cases
where the chopper is large, it may function
as a secondary impeller.
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Granulation process parameters

Water Addition Rate and Method

Water Addition Rate is critical to granule quality.
Generally water addition rate is chosen such that
local over wetting of the powder mass is not a
concern and at the same time the addition rate is
fast enough to accommodate processing times
(~2 5 mins for water addition).

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Granulation process parameters

Massing Time
Massing time is normally in the order of 1 to 10
minutes. Long massing times (> 20 mins) may
lead to decreased dissolution rates due to
decreased disintegrant function or due to the
formation of denser granules.
Load of the Mixer
Generally, the load of the mixer is less than
two-thirds the volume of the mixer.

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Table 1 : Steps in Different Methods of Tablet
Manufacture (Unit Operations)

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Table 2 : Relative merits and demerits of
different granulation process

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 Granule size
enlargement and
interpretation of
size data

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 Introduction
The particle size of a granulation is known to affect the
average tablet weight, tablet weight variation,
disintegration time, granule friability, granulation
flowability and the drying rate kinetics of wet granulation.

The principal intent of particle size measurement is to

establish the true particle size frequency distribution .

Particle size distribution can easily determine for

powders or granulations containing spherical particles
rather than irregular in shape because the size of a
sphere is uniquely determined by its diameter.

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A. Methods of Data Presentation
for Particle size distribution Table1: Size distribution data for a
hypothetical tablet granulation
Tabular Presentation
The most precise and explicit way of
presenting size distribution data is by tabular
form. The frequency data table 1 are
represented by weight rather than by
number. The size distribution can be defined
in terms of the weight or number of particles
within a given size range.

Graphical Presentation

Histograms, size frequency curves, and

cumulative frequency plots represent the
most common ways of graphically illustrating
size distribution data.

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Frequency Histograms

The simplest graphical

form is a histogram plot in
which frequency of
occurrence is plotted as a
function of the size range.
A histogram plot of the
data represented in Table
1is shown in Figure 1

Fig1 :Histogram plot for the size

frequency data given in a Table 1

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 Cumulative Frequency
Curve

Cumulative frequency
curves are arrived at by
plotting the percent of
particles less than (or
greater than) a given
particle size versus
particle size.

Fig 3 : Cumulative frequency plot for the

data presented in Table 1

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B. Method for determining Particles Size distribution

Particle size can be determined by

Sieve analysis
Optical microscopy
Laser light scattering
Sedimentation
Adsorption methods
Electrolytic resistivity (Coulter Counter)
Permeability

Dry sieve analysis and optical microscopy are

generally the most popular methods for determining
size distribution of granules.
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Sieve analysis: Sieving is the simplest and most widely
used method. Two factorsparticle size distribution and
shapecan be obtained by sieve analysis. The more
notable factors influencing the performance of the sieving
operation are given below:

Sieve load and sieving time

Screen movement, particle orientation, and particle
shape
Aperture size and variations
Sampling of material

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Microscopy: Microscopy provides a more exact
measurement of particle size, but it is a labor-sensitive
method.
Computer aided image analysis techniques have been
employed to simplify the method.

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Characterization of
granule shape

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 Granule Shape
Particle shape can have a significant effect on the bulk
properties of a powder.

Shape of particles may be assessed descriptively by

terms such as
spherical,
elongated,
acicular,
angular etc.

Particle shape can be quantified by different methods

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Spherical particles flow better, pack better, and
have a lower surface to volume ratio.
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 Granule Shape summary
Factor Effect on particle
Volume shape factor , v For sphere v equals to /6 . As
the volume shape
factor increased , bulk density increased,
because more spherical or more regular-shape particles
produce the closest packing arrangement

Surface Shape factor,s a sphere , s =~ 3.14.

Shape Co-efficient , v s shape coefficient for a sphere would be 6.0. As the

particle become more irregular in shape particle the
values of v s increases.

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 Granule density and
packing characteristic

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Terminology Definition

Granule density Granule density = granule weight

granule volume

Bulk density Bulk density = mass of the powder (w)

bulk volume (Vb)

True density it is the weight of material it self

Tapped density ratio of mass of powder to tapped volume.

Porosity Porosity is a measure of the void spaces in a material,

and is a fraction of the volume of voids over the total
volume, between 01, or as a percentage
between 0100%.

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 Granule density
The bulk density is determined by measuring the
volume of a known mass of powder, that has been
passed through a screen, into a graduated cylinder.

Granule density may influence

> compressibility,
> tablet porosity,
> dissolution and
> other properties .

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 Granule density
Dense particles are generally less cohesive than
less dense particles of the same size and shape.

Dense, Hard granules may require higher compressible

loads which in turn has the potential of increasing the
tablet disintegration and drug dissolution time.
Even if the tablets disintegrate rapidly, the harder,
denser granules may dissolve less rapidly.

Bulk density largely depends on particle shape.

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 Granule density
For powders having comparable true densities an
increase in bulk density causes a decrease in
porosity.

This increases the number of inter particle contacts and

contact areas and causes an increase in cohesion .

Particle become more spherical in shape, bulk density

increases.

Granule size increases , bulk density decreases.

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 Granule density
Table 1: Scale of flowability

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 Packing characteristic
Bulk density and porosity are used to characterize packing geometry of
particles or granules. Packing studies are carried out by filling a volumetrically
calibrated cylinder with powder and tapping it.

Two ideal geometric packing of spherical particles

1. Closest or rhombohedral packing
2. Most open, loosest or cubical packing.

Closest or rhombohedral Cubical arrangement

Particle spherical in shape, bulk density increases- closely pack

Granule size increases bulk density decreases.- higher porosity loose packing
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 Packing characteristic
Theoretical porosity of powder consist of uniform sphere in

Closest packing- 26%

Loosest packing- 48%

Real powder have porosity in between 30 to 50%.

In suspension, porosity may above the theoretical max limit 48%.

Crystalline materials porosity- <1% (under force 10000 lb/in2)

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Factors affecting packing geometry

1. Particle size and size distribution

2. Particle shape and texture

3. Surface properties

4. Handling and processing conditions

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Electrostatic properties
of tablets

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 Electrostatic Properties
Interparticulate forces acting between the granules/
solid particles can affect the flow properties of a solid.
Interparticular attraction makes the flow property
poor. Electrostatic repulsion may facilitate flow of a
powder bed.

Electrostatic force arises during mixing and compaction

due to triboelectrostatic charging.

Electrostatic interaction determine the:

Flowability and
Compactability of powder

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 Electrostatic Properties
Electrostatic charge highly influences bulk density.

Electrostatic forces contributes very little to the overall

strength of a granule.

Triboelectrostatic charge have a negative affect on

uniformity of the bulk density and consequently the
uniformity of dose.

Several methods have been suggested to

minimize the effects of electrostatic charges.

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Rheological properties
of granules

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 Rheological Properties
Common methods for determining powder/granule flowability

(a) angle of repose,

(b) Hausner ratio

(c) shear strength determination and

(d) hopper flow rate measurements.

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 Angle of Repose
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 which is formed when the
powder is passed through a funnel-like container.

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 Angle of Repose
The angle of repose is determined
by the following equation :

Where
= angle of repose.
H=height
R= Radius of base of the
conical pile

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 Angle of Repose
Table: Flow properties and corresponding angle of repose

The powders that can flow well give small angle of repose.

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Factor influencing angle of repose
Several factors and granule characteristics have been
studied for their effect on the angle of repose such as
particle size ,
use of glidants ,
moisture effects, and
particle shape.

The angle of repose is best suited for particles

150m. In this size range , cohesive effects will be
minimal .

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Factor influencing angle of repose

Particles larger than 250 micron are usually relatively

free flowing,
Particle size falls below 100 micron powders become
cohesive and flow problems are likely to occur.
Powders having a particle size less than 10 micron are
usually extremely cohesive and resist flow under gravity,
except possibly as large agglomerates.

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 Title of Slide
I. In a general sense, the repose angle normally increases as
particle size is reduced and this effect is usually dramatic small
particle size range.
II. the angle of repose of goes through a minimum and the
increases as glidant concentration increases.
III. when materials that take up moisture from the atmosphere are
exposed to high humidities , the materials generally become
more cohesive , cake in their container and exhibit very poor
flow characteristics.

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 Summary
Factor influencing angle of repose
Factor Effect on angle of repose

Particle size Particle size- higher angle of repose

Fines (up to 15%)-increase angle of repose

Particle shape Rough & irregular surface- higher angle of repose

Glidant concentration Glidant at low concentration- angle of repose

Moisture content higher the moisture content greater the cohesion &
adhesion exhibit very poor flow characteristics

Shape factor shape co-efficient increases - bulk density -repose

angle increases.

Lower the angle of repose- better the flow property

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Granule strength and
friability

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 Granule Strength
Measurements of granule strength are aimed at
estimating the relative magnitude of attractive
forces seeking to hold the granule together.

Granulation strength and friability are

important, as they affect changes in particle
size distribution of granulations and
consequently compressibility into cohesive
tablets.

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 Friability
Compression strength & friability measurement:

Directly crushing/compression strength : In this test,

a granule is placed between anvils and the force
required to break the granule is measured .

Friability of granulations : In this measurement, a

friabilator is charged with the granules to be tested and
then rotated a set number of times. The percentage loss
of mass for a particular size is usually the value that is
represented in a granule friability analysis.

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 Moisture Control
Moisture could affect flow of granules, tablet
compression, tablet disintegration, crystal habit,
capsule brittleness, chemical stability, and many
other properties.

Moisture content is generally measured using moisture

analyzer during product development; a thin layer of
sample is heated at a set temperature until it reaches a
constant weight and the results are expressed as LOD.

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 Moisture Control
Too much moisture in granulation will result in one set of
problems (sticking, picking, microbial growth,
stability issues) while too little will result in a different
set of problems (lamination and).

Tablet made using low moisture content granulations

when exposed to higher humidity may increase in
hardness and disintegration of tablet.

Increasing moisture content increased the granulation

compressibility. ALL these statements may not be
true, reverse result may obtained
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 References :
1. Pharmaceutical Dosage forms: Tablets H.A LIEBERMAN

2. Pharmaceutics: The science of dosage form design

Michael E. Aulton,

3. Handbook of Pharmaceutical, Granulation Technology

Taylor & Francis Group, LLC

4. The Theory and Practice of Industrial Pharmacy

Leon Lachman, Herbert Lieberman, Josef Kanig

5. British Pharmacopoeia 2007

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 Title of Slide
Slide Text

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