Powder technology

Powder Technology

Powders are a complex system; in the field of powder technology a material can be classified as
a powder if it is made up of a dry discrete particles with a maximum dimensions of less than
1000 µm interspersed with void space.
Powders are used as a starting point in the manufacturing of most pharmaceutical dosage forms
like tablets, capsules and syrups. Furthermore, it is used as a pharmaceutical dosage form that
describes a formulation containing a drug powder mixed with other powdered excipients to
produce the final product. These powdered preparations may be dispensed as
 Bulk powder for internal use
 Divided powders (single dose preparation sachet) for internal use
 Dusting powder for external use
 Insufflations for ear, nose and throat use
 Antibiotic syrups
 Powders for injection
The fundamental properties of powders differ from that of other physical state of matter and their
physical nature makes it difficult to characterize. They basically non homogenous, similar to
solid in that they can withstand some deformation when not pressed too hard (has the elastic
properties of a solid) and to liquid in that they can flow in all directions under certain
circumstances and to gas in that they can be compressed to a certain degree. But unlike solids,
powders can undergo density changes. Consequently, powder has one set of properties when it's
stagnant and another set of properties when it's moving.
Accordingly methods used for studying liquid and solids will require some modification if they
are to be used to study powders.
There are three different approaches for studying the properties of powders. The first approach is
to consider the powder bed as a continuum without discrete structure and to study the
relationship between stress and strain by similar techniques to those employed for studying the
mechanical properties of solids and liquids.
The second approach is to consider the powder bed as a collection of a large number of discrete
individual particles which are separated from each other by void space, and the interaction

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between the individual particles are summed statistically to determine the bulk properties of the
powder. Though in theory it should be possible to determine the properties of idealized powder
bed containing mono-sized smooth spherical particles. This method is very difficult and complex
to apply to a real powder system since powder materials generally contain large number of multi-
sized, rough surfaced and irregular shape particles.
The third approach is to attempt to explain the properties of powders in term of an atomistic
model i; e in term of the forces between the atoms composing it, but again the problem is very
complex.
The continuum approach has received more attention than the other two methods due to its
simplicity in making predictions about the properties of the powders and subsequently testing
these predictions by experiments.

Significance of particle size

Micromeritics is a term coined to describe material properties such as particle size, shape,
specific surface area, and porosity. The size of the particle can directly influence the
properties of the powder and hence the properties of the final product therefore, the state of
subdivision of a drug powder is a primary factor to be considered in the preparation of the
dosage form.

 Particle size is one of the most important properties affecting dissolution rate and
bioavailability of poorly soluble drugs.
 Particle size of excipients also plays a key role in determining the product and process
attributes such as content uniformity, flowability of powders, water uptake and retention
during granulation, and lubricant effectiveness

 The particle size can affect the physical, chemical and physiological properties of drugs,
 In suspension the behavior and flow will depend on the particle size

 Particle size has a great influence on the mixing of solid substances and on their stability

 Particle size can affect the granulation process and the quality of granules produced

 The processes of separation of solid from liquid like filtration and sedimentation, are
influenced by particle size

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 During tablet compression the flow of powder from the hopper to he die cavity is affected
by particle size

 Mass transfer processes like drying and solution are affected by the size of the particles

 The adsorption capacity of powdered material is affected by particle size

 The size of drug particles have a significant influence on their absorption

Definition of a particle size

In defining the size of the particle the spherical particle is uniquely determined by its
diameter. For example a powder can be supplied with a statement saying that it has a mean
particle size of 40 µm. This definition applied one linear dimension which is true in case the
powder consists of spherical particles. However, powdered materials consist of irregular,
three-dimensional particles, the dimensions of these particles can be derived form various
characters like weight volume, surface area and sedimentation velocity. Therefore parameters
such as surface area and volume of particles can be fixed with the diameter and can be used
for determination of the particle size.
In practice, powders consist of non-spherical, irregularly shaped particles, which have a
definite surface area and volume but its length varies with its orientation. Therefore, the size
of non-spherical particles can be defined more conveniently as the diameter of the sphere that
has the same surface area of the particle (surface diameter), or the same volume (volume
diameter) or the same projected area (projected diameter) or the same density (stockés
diameter) or sieve diameter.

Particle size Distribution

The knowledge of particle size distribution is more important than the mean particle size and
the median particle size. It is important to express the range of the particles in the group and
the distribution of the sizes within the range. These can be done by statistical method e. g.
standard deviation or by graphical method like size distribution curves, histogram, % oversize
and % undersize.

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Particle size reduction

Particle size reduction (comminution) is the mechanical process of reducing the size of the
particles or aggregates thus, it includes a variety of operations like cutting, crushing, milling
and micronizing which depends primarily on the type of equipment employed. Size reduction
is conducted mainly to achieve the following objectives
1. To produce smaller particle size (e.g. for preparation of suspension)
2. To increase surface area (to improve absorption or mass transfer).
3. For extraction of drugs (to expose the plant cells to the solvent).
4. To reduce the bulk of the materials (reduce storage area and transportation cost).

Factors affecting size reduction

Pharmaceutical industry uses a variety of materials including chemical substances, animal

tissues and vegetable drugs that may be hard like seeds, fibrous like roots or spongy like
peels. The selection of the appropriate method involves consideration of the material
properties that may influence the process. Certain properties could affect size reduction
process include:

1. Hardness
Hardness is a surface property of the material thus it is possible for a material to be very
hard but if it is very brittle also then size reduction may present no special problem. In general
the harder the material the more difficult to reduce in size.
Moh’s hardness scale classifies material substances according to their hardness into three
classes (soft, intermediate and hard). The scale (hardness number) ranged between 1 to 10
and the material substances were classified as following:
1. Soft substances between 1 to 3.
2. Intermediate substances between 4 to 7.
3. Hard substances higher than 7.

2. Toughness
Toughness is more important than hardness. A soft but tough material may present more
problems in size reduction than hard but brittle substances. Many pharmaceutical materials,
particularly in fibrous drugs, present toughness problem.

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Toughness can be reduced by treating the material with a liquefied gas such as liquid
nitrogen, by this means, a substance can be cooled to a –100 – 150 °C in which tough
substances become brittle and will break like glass.

3. Stickiness
Pharmaceutical substances that are gummy or resinous may cause a considerable
difficulty in size reduction because it may adhere to the grinding surfaces or the mesh of the
screen, especially if the methods of size reduction generate heat. Complete dryness and
addition of the inert substances could help.

4. Moisture content
It has an important influence on a number of properties that affect size reduction e.g.
toughness, hardness and stickiness. In general a material moisture content of less than 5% is
suitable for dry grinding and that of more than 50% is suitable for wet grinding. However an
increase of water concentration reduces the rate of size reduction.

5. Abrasiveness
It is a property of hard materials e.g. minerals and could result in contamination of the
final product. This problem may limit the use of that type of machinery.

6. Softening temperature
Many of size reduction processes result in generation of heat, which may cause some
substances like stearic acid and fats containing drugs to soften. It is possible to prevent this
problem by cooling the mill by water jacket or by using liquefied nitrogen.

Theories of size reduction

During particle size reduction only very small amount of the energy that put into the machine
actually affect size reduction which estimated as 2%. The reminder energy being lost in
elastic deformation of particles, plastic deformation of particles without fracture, deformation
to initiate cracks which cause fracture, deformation of metal machine parts, interparticle
friction, particle-machine wall friction, heat, sound and vibration.

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Several theories have been postulated in order to relate energy input to the degree of size
reduction produced. Rittingre`s hypothesis stated that the energy, E, used in size reduction is
proportional to the new surface area produced Sn

E = KR(Sn – Si)

Where Si is the initial surface area and KR is the Rittingre`s constant of energy per unit area.
Kick`s theory postulated that the energy used for size reduction of particles of equivalent
shape is proportional to the ratio of initial and final particle diameter

E = KK log di/dn

KK is Kick`s constant of energy per unit mass, di is the initial particle diameter and dn is the
new particle diameter.
Bond`s theory stated that the energy used in crack propagation is proportional to the new
crack length produced
E = 2KB (1/dn – 1/di)
Where KB is Bond`s work index and represents the variation in material properties and size
reduction methods with dimensions of energy per unit mass.

Mechanisms of particle size reduction

There are four main methods of size reduction involving different mechanisms:
1. Cutting
The material is cut by means of a sharp blade or blades. e.g. guillotine, scissors and
cutter mill
2. Compression
The material is crushed by application of pressure e.g. nutcrackers, roller mill
3. Impact
It is occur when the material is more or less stationary and hit by an object moving at
high speed or when a moving particle strikes a stationary surface. Impact mill produce
sharp irregular particles, which may not flow readily. e.g. hammer mill
4. lAttrition

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The material is subjected to pressure as in compression but the surfaces are moving
relative to each other resulting in shear forces, which break the particles It produces free
flowing particlese.g. roller mill

Size reduction methods

The term mill is used normally for machines that used for size reduction. There are many
different types of size reduction techniques but the milling equipment used can be classified
according to the principal method employed to produce size reduction. Generally a mill is
consisting of three parts:-
A feeder (to deliver materials)
A grinding chamber (contain the grinding mechanism)
A discharge

The principle of action depends on size reduction mechanism and the choice of the proper size
reduction technique depends on the properties of the solid material and on the specification of
the product.
A mill may operate in a batch process or in a continuous process. The batch can be defined as
(a quantity of material produced in a process and expected to be homogeneous within
specified certain limits). In batch processing the batch size is determined by equipment
capacity.
In continuous processing where input rate is equal to the out put rate, the size of the batch is
determined by the amount produced within a certain time period.

Open circuit milling

The operation is carried out so that the material is reduced to the desired size by passing it
once through The mill.

Closed circuit milling

In this process the discharge is passed through a size separation device or classifier and the
over size particles are retained in the grinding chamber for further size reduction. (Most
valuable in reduction to fine or ultra fine size).

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I. Cutting methods e.g. Cutter mill

It consists of a series of knives attached to a horizontal rotor, which act against a series of
stationary knives attached to the mill casing. The lower part consists of a screen so that the
material is retained in the mill until a sufficient degree of size reduction has been affected.
This method is useful in the production of coarse degree of size reduction of dried granulation
prior to tabletting and of fibrous drugs like roots, peels or parks prior to extraction.

Feed

Rotating knives

Stationary knives

Rotor

Product
Cutter Mill

II Compression methods
On small scale size reduction by compression can be carried out by mortar and pestle. In the
pharmaceutical industry The most commonly used mill that applies compression is roller mill.
Roller mill has two cylindrical rolls of stone or metal mounted horizontally and capable of
rotation on their longitudinal axes.

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material
cylindrical roll

milled material
Roller Mill

Usually one of the rolls is driven directly while the second runs free (by friction). The gap
between the rolls can be adjusted to control the degree of size reduction.
Roller mill is used for crushing seed prior to extraction of fixed oil or bruising soft tissues to
aid solvent penetration in extraction.
Another forms of compression mill are end runner mill and edge runner mill which are
mechanized form of mortar and pestle In the end runner mill the weighted pestle is turned by
friction of material passing beneath as a mortar rotates under pressure.

Weight

Pestle
Rotating mortar

End-runner mill

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The edge-runner mill has the pestle equivalent mounted horizontally and rotates against a bed
of powder so that size reduction occurs by attrition as well as compression

Pestle equivalent or muller

Mortar
Edge runner mill

III. Impact method e.g. hammer mill

It consists of a rigid metal case enclosing a central shaft to which four or more hammers
attached. During milling the hammers swing out radially from the rotating shaft. The lower
part of the casing consists of a screen through which material can escape when sufficient size
reduced. It operates in a high speed (up to 10000 rpm) and a size reduction between 20 and 40
µm could be obtained.
Hammers

Feed

Screen

Product
Hammer Mill

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Advantages of hammer mill

1. Rapid and capable of grinding different types of materials
2. The product can be controlled by variation of motor speed, hammer type and size and
shape of screen
3. A continuous operation
4. No surfaces are against each other so there will be no risk of contamination

Disadvantages of hammer mill

1. The high speed of operation causes generation of heat which affect thermo-labile
materials
2. The rate of feed should be controlled otherwise the mill may be damaged
3. Because of high speed operation the hammer mill is susceptible to damage by stone or
metal in the feed

Another technique that applies impact mechanism is vibration mill. Vibration mill is filled to
approximately 80% of its total volume by porcelain or steel balls. During vibration the whole
body of the mill is vibrated and size reduction occurs by repeated impaction.

Flexible coupling to drive motor out of balance weight

Feed in Milling balls

Spring mounting
product out

Vibration Mill

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IV. Attrition method e.g. roller mill

Roller mill uses the principle of attrition for the size reduction of solids in suspension, pastes
or ointments. It consists of two or more rolls mounted horizontally with a very small, but
adjustable gap between them. The rolls rotates in different speed so that the material is
sheared as it passes through the gap. The method is very effective for size reduction and
dispersion of solid in semi-solid media.

Combined Impact and attrition method

The two mechanisms can be combined in two types of mills, ball mill and fluid energy mill.

Ball mill
It consists of a hallow cylinder (of different sizes) mounted such that it can rotate on
horizontal and longitudinal axis. The cylinder contains balls that occupy 30 – 50% of its total
volume, ball size being dependent on the feed and mill size, for example a mill 1 m in
diameter might contain balls with a diameter of 75 mm. Mills usually contain balls with many
different diameters due to self attrition and this help to improve the product since large balls
break down coarse particles and small balls help to form fine product particle by reducing
void space between them.

Ball mill

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The amount of material in the mill is of considerable importance, it is expressed as a material

to the void ratio. In general the milling efficiency is increased as the amount of the material
increased until the void space is full, further increase of the feed reduce efficiency of the mill
due to cushioning effect. However, too little cause abrasiveness. In addition the speed of
rotation is also important. At low speed the balls will slide or roll over each other and only a
negligible amount of size reduction will occur only by attrition (see figure a below). As speed
increased the balls are carried up the sides of the mill and fall freely onto the material
producing impact action, which responsible for the most of size reduction. The optimum
speed is the speed at which the balls just begin to centrifuge with the mill (the centrifugal
force is equal to the weight of the balls). i.e the balls are carried almost to the top of the mill
and then fall in a cascade across the diameter of the mill (see figure c below) producing
maximum size reduction by impact and attrition between the balls. However, at high speed
the balls will thrown out the walls and no grinding will occur (see figure bbelow).

a b c

The size and type of the ball has an influence on the size reduction, smaller balls give slower
but finer grinding than larger balls because they provide small voids. It has been suggested
that the optimum size of the balls are approximately proportional to the square root of the size
of the feed.
D ball2 = K d
Where K = 55 for hard materials and 35 for soft materials

Smaller balls facilitate production of fine material but they are ineffective in processing large
size feed. The weight of the balls of a given size effect size reduction, as the weight increased
the powder fineness is increase.

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The weight of the balls can be increased by using balls with higher density or by increasing
the number of the balls.

There are some modified types of ball mill which include

I. Pebble mill, where pebbles are used instead of steal balls
II. Rod mill, where rods or bars are used instead of steal balls. It used specially for sticky
materials (the sticky materials will hold the bars together then on rolling the bars will
pull apart because of their greater weight)
III. Tube mill, is a modified form of ball mill, the length is about four times the diameter
and the balls are smaller than those used for ball mill.
Advantages
1. Capable of grinding a wide variety of material
2. It can be used in completely enclosed form, which make it suitable for toxic materials
3. It can produce very fine powder
4. Suitable for wet and dry grinding
5. It can be used for continuous operation
Disadvantages
1. Wear occur and could result in contaminated products
2. Soft or sticky materials may cause problems by caking on the sides of the wall

Fluid energy mill

Fluid energy mill is used when fine powders are required e.g. antibiotics, vitamins and
sulfonamides. It consists of a loop of pipe which has a diameter of 20 to 200 mm depending
on the over all height of the loop which may be up to 2 m.
A fluid, usually air is injected at high pressure through nozzles at the bottom of the loop
giving rise to a high velocity circulation in a very turbulent condition. Solids are introduced in
the stream where impact and attrition occur between the particles. A classifier is incorporated
in the system so that particles are retained until sufficient fine. During grinding particles are
suspended and conveyed at high velocity in air or steam, which passed through nozzles at 100
to 150 pound per square inch (psi). Air is usually used because most pharmaceuticals have
low melting point or thermolabile.
Fluid energy mill can reduce the particles from 1 to 20 µm, the size reduction occurs mainly
by interparticulate attrition. The feed should be pretreated to 100 mesh particle size to enable
the process to yield a product as much as 5 µm or less.

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Advantages
1. The particle size of the product is smaller than that produced by any other method
2. Expansion of air lead to cooling counteracting the usual friction heat which can effect heat
sensitive materials
3. No abrasion of the mill (no contamination) since reduction occurs by inter-particulate
attrition
4. For very sensitive materials it is possible to use inert gas
5. The classifier permit close control of particle size

Centrifuging action through

course particles outwards

Classifier removes fine

particles and fluid

Solid inlet

Zone of turbulence

Fluid inlet jets

Fluid energy mill
The Objectives of producing fine particles
1. Increase surface area (increase dissolution and enhance absorption of insoluble drugs).
2. Allow excess to lungs (dry powder inhalation).
3. Prompt mixing (interactive mixture)
4. Prompt suspension stability
5. Improve ointments, creams and pastes

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Wet grinding (levigation)

In this process particle size reduction is carried out on a paste of material instead of
processing dry solid. It has a limited application because it demands a material that is already
of a small particle size and it is insoluble in the fluid. The choice of wet or dry grinding
depends on the use of the product and its subsequent processing. However if the product
undergoes physical or chemical change it is recommended to use dry milling.

Advantages
1. The powdered substance contains less fine
2. The capacity of the plant is greater
3. The problem of dust is eliminated
4. Materials is easily handled in form of suspension, and in many cases will flow under
gravity or it can be pumped
5. Size reduction and mixing can be combined for products made in form of suspension
6. Lower power consumption.

Colloid mill
It consists of high speed rotor capable of rotation up to 20000 rpm and stator (static cone)
with a conical milling surface between them, with an adjustable clearance ranging from 0.002
to 0.03 inch. The rotor and stator may be smooth surfaced or rough surfaced. Rough surfaced
mill are usually useful with fibrous materials (to prevent interlock or clog of the smooth
surfaced mill). It causes depression of coarse material by shearing in the narrow gap between
the rotor and stator.
Hopper

Rotor
Stator
Product
Shaft
Colloid mill

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The material to be grinded should be pre-milled as finely as possible in order to prevent

machine damage. It is used for processing of suspension and emulsion.

Selection of size reduction methods

Different mills give different product sizes from the same starting material. The used to
which the powder will be put and the cost of size reduction controls the degree of size
reduction. The following are typical methods used for various size ranges
-large pieces cutter or compression mill
-coarse powder impact mills
-fine powder combined impact and attrition mill
-very fine powder fluid energy mill

The choice of the mill depends on

1. Properties of the powder to be milled
2. Product specification (size, size distribution, moisture content and physical and chemical
properties).
3. Capacity of the mill and production rate requirement.
4. Versatility of operation (wet or dry grinding, rapid change of speed and screen and
safety).
5. Dust control (loss of costly drugs, health hazards and contamination of plant).
6. Sanitation (ease of cleaning and sterilization).
7. Auxiliary equipment (cooling, dust collection and forced feeding)
8. Batch or continuous.
9. Economical factors (cost, power consumption, space occupied and labor cost).

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Particle size analysis

The analysis of particle size is of great importance in different steps of drug development. For
instance, the particle size of a new chemical entity (NCE) has to be evaluated with respect to
whether it has a significant effect on dissolution rates, bioavailability, stability, processability,
or drug product content uniformity. Furthermore, the bulk properties and behavior of a
material in different unit operations used in drug manufacturing depend to a great extent on its
particle size distribution.
Various techniques for measuring the particle size distribution of powders exist and the choice
of method has to be made carefully based on material characteristics and the type of
information required.
In any particle size measurement, representative samples of the bulk powder must be analyzed
i.e. it has to be confirmed that the sample has to represent the particle size distribution of the
bulk powder. The definition of the term “sample” is expressed as “a portion of the whole,
selected in such a way as to be truly representative of the whole.
In many circumstances the knowledge of the distribution of sizes is more important than the
mean particle size. The range of particle size in a group can be easily expressed by graphical
method in which data from a particle size analysis can be presented. The test will yield a
series of fractions of various size ranges, which can be plotted as following:
 % Oversize which presents all particles larger than the specified range (begin with finest
values)
 % Undersize which presents all particles smaller than the specified range (begin with
coarsest values)
 Distribution curve which presents the frequency with which each size occur
 Also size frequencies can be presented as a histogram

% Oversize
% Undersize

Particle size Particle size

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Distribution curve Histogram

% %
W/W W/W

Particle size Particle size

Methods of particle size analysis

Naturally occurring solid particles and milled solids have irregular shapes and their sizes
varies within the range of the largest and smallest particles. In order to define the size
distribution of a powder bed or to compare the characteristics of two different powders (or
more) the size distribution can be broken down into different size ranges.
The data obtained after particle size analysis test can be presented in tabular form or graphical
form. Tabular form is the most precise method. The graphical method is commonly used
because it is more concise and permits easy visualization of the mean and ske wness of
distribution.
Data graphical presentation such as distribution curve or histogram yields a graph with a
mode (peak frequency value), which divide the curve into two halves:-
Normal distribution (two identical halves)
Positive skewed curve (frequency curve with an elongated tail toward higher values)
Negative skewed curve (frequency curve with an elongated tail toward smaller values)
Bimodal curve (frequency curve with more than one mode)

In cumulative frequency distribution curves (sequentially adding the percent frequency

values) size distribution and the degree of skewness can possibly be conducted by
determination of inter quartile coefficient of skewness (IQCS).
:

(c - a) – (a – b)
IQCS =
(c - a) + (a – b)

Between –1 to +1,
0 = normal distribution
b a c

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There is no known method of defining the size of irregular particle in geometric terms. The
definition of the particle size depends on the measurement method. However, particle size
analysis is performed using one of the following techniques

I. Sieve methods
Sieving is a go/no/go test by which the powder is divided into two fractions, above the
specified size and below the specified size. In order to obtain a distribution of particle size it
is necessary to carry out a test by using a nest of sieves where the coarsest sieve is placed on
the top so that the powder is passed successively over finer sieves and a serious of fractions
obtained. Sieving is the most widely used method for measuring particle size distribution
because it is simple, inexpensive, rapid and reproducible (little variation between operations).
The lower limit of sieving is generally considered as 50 µm {The International Organization
of Standardization (ISO) set sieve diameter of 45µm as a lowest sieve and 1000 µm as a
highest}.

Sieve Vibrator

Sieve

 Consists of pan with a bottom of wire mesh

with square openings
 Two standard sieves, Tylor and US standard

It is difficult to obtain accurate results from a sieve analysis for a number of reasons:
1. Particles can be attracted electrostatically to form aggregates
2. Humidity can affect particles of hygroscopic materials and could lead to aggregation

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3. Particle shape has a great influence. Spherical particles do not exhibit problems during
sieving whereas, irregular shaped particles need certain treatment to obtain successful
sieving.
4. Particle size distribution
5. The shape of the aperture could affect sieving process. The wire meshes usually have
square aperture but rectangular is also used. For perforated sieves a circular openings are
used.
6. Standardization of the technique is essential especially with regard to the end point.
7. It is necessary to cause some disturbances of the powder bed to enhance sieving e.g.
shaking or vibration.

Results of sieve analysis are best presented in the form of oversize or as a histogram.

II. Microscopic method

The use of microscope to examine and measure particles is very effective procedure for
particle size analysis, which provide a direct measurement of the particle size of about 0.4 to
150 µm. It is considered as the most directly method of particle size distribution
measurement. The test is carried out using calibrated micrometer eyepiece or by using
graticule (eyepiece with a number of opaque and transparent circles). Particles are compared
with the sets of circles and sized according to the circle most closely corresponding to the
equivalent diameter being measured.
British standard recommend counting at least 625 particles. If the size distribution is wide it
may be necessary to count more particles. If the particle size distribution is narrow, as far as
200 may be sufficient.

Disadvantages of microscopic method

1. Particle shape. It is necessary to decide on one linear dimension to represent the particle.
2. Particle position. The particle will assume the position of maximum stability, this means
that particles that are laminar or that has a plate-like structure will appear to be larger than
they would be if tested by other methods.
3. Aggregation. If the particles aggregate on the slide they will give inaccurate results.
4. The speed of the method. The process is slow.
5. Sampling. A special technique must be used to obtain a small number of particles on the
slide.

III. Image analysis (IA)

In image analysis the basic equipment components include one form of microscope, a camera,
frame grabber (optional depending on the type of camera), computer, and an IA software.

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With a suitable stereomicroscope the size range used in analysis can vary approximately from
1 micrometer range up to a few millimeters. It alone permits the direct characterization and
visual information of particles in the sample. The data interpretation is usually uncomplicated
since the images analyzed are stored and any discrepancies in results can be controlled by
visual inspection of particles measured. The largest sources of errors in IA are probably
sampling and sample preparation i.e. the dispersion of the powder

IV. Fluid classification methods

Particle size of powders in the sub-sieve range can be analyzed depending on the
movement of the particle in the fluid. It is used over a size range from 1 – 200 µm. By this
method separation of particles of various sizes depends on particle velocity rate of
sedimentation), hence the division of particles into fractions depends upon the time during
which sedimentation is allowed to occur.
The behavior of a sphere in a fluid can be expressed by stocke`s law which is applied to
a single spherical particle falling under streamline conditions in a stagnant fluid as following:

µ = d²(s -i) g/18

18 
d stoke = (s -i) g
µ
Where
µ is the average velocity of sedimentation of particles (distance / time)
d is the mean diameter of the particle
s is the density of the solid particle
i is the density of the fluid phase
 is the viscosity of the liquid phase

The density of the solid and the density and viscosity of the fluid will be constant so that the
important conclusion from stocke`s law is that the terminal velocity of any particle is
proportional to the square root of the diameter of the particle size.
In practice powder suspended in fluid consists of a large number of irregular particle,
furthermore effects can be arise from eddy currents in the fluid, rotation of the
particle,.Brownian movement (zig – zag movement) or from electrical charges leading to
aggregation of particles.
Nevertheless, stocke`s law is adequate to give an estimate of the particle size.

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Practically, there are many ways of determining the settling velocity. All use the sampling
technique, whereby a concentration of the particles at a particular level can be observed and
compared with the starting concentration and the settling velocity determined.
Methods that can be used may be:
1. Cumulative, measure the total amount of the material that has settled out since the
beginning of the test (by using sedimentation balance)
2. Incremental methods, when the amount of material that has sedimented in particular time
increment can be determined, various methods are used which include:
a. Pipette method, a sample of a suspension is removed from a known depth below the
surface by means of pipette and the solids determined, usually gravimetrically.
b. Hydrometer method, when particles settle out the density of the suspension
decreases which can be observed by hydrometer or by divers (small floats of
suitable density which sink as the density of the suspension changes.
c. Pressure method, a sensitive manometer is attached to the side of the column at a
known distance below the surface as the solids settle out past that point, the density
of the column changes and shows as a decrease in the manometer reading..

Suction to fill pipet

10 ml

Two way stopcock

Pipet
Scale

Particle size analysis 23

 Powder technology

V. Conductivity method, (coulter counter)

In this method the powder sample is dispersed in an electrolyte (electrically conductive
fluid) to form a dilute suspension. The suspension will flow through a suitable aperture with
an immersed electrode on either side and the particle concentration is arranged so that only
one particle travels through the aperture at a time. The electrode monitors the changes in
electrical signal, which occurs when the particle occupies the orifice and displaces its own
volume of electrolyte. The volume of suspension drawn through the orifice is determined by
suction potential created by mercury thread rebalancing in convoluted U tube. This electrolyte
volume causes change in electrical resistance between the electrodes, which is proportional to
the volume of the particle. The change in resistance is converted in to a voltage pulse, which
is amplified and processed electronically. The result is compared with pre-calibrated limits to
split a particle size distribution into many different sizes.

Advantages of coulter counter

1. The results is expressed in terms of particle volume from which it is a simple matter to
calculate the diameter of the sphere of equivalent volume.
2. It can operate with particles between 0.5 – 1000 µm.
3. The operation is very rapid.
4. Results obtained are more reliable than the other methods, since large number of particles
are counted.

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VI. Laser diffraction

Low angle laser light scattering with an applicable range of 0.1 – 3000 nm is used for
particle size measurement. The method relies on the fact that diffraction angle is inversely
proportional to the size of the particles. Light scattered in the forward direction can often be
accurately approximated by diffraction theory. During particle size distribution measurements
by laser diffraction samples can be suspended in air or liquid. Measurements are based on the
interaction of the laser light with the particles. Any interaction will cause light to scatter in
forward direction with small change in angle, this phenomenon is known as Fraunhofer theory
and produce light intensity pattern proportion al to the diameter of the particle.
d = 1.22 / Sin 
Where
d is the particle diameter
 is the wave length of the laser light
 is scatter angle

Optical measurements for particle size analysis that based on the measurement of laser light
scattered by the particle in a forward direction have become a popular and a standard
technique and this class of instruments has become generally known as laser diffraction
instruments. Compared with other methods laser diffraction has the advantage of high speed,
good reliability and reproducibility. It is used for size determination of both solid – liquid
system and gas – solid system. Generally inadequate sample dispersion is a major source of
error, leading to a leak of repeatability and reproducibility.

Sample inlet
Laser Lens Detector
Beam

Measuring zone
Sample outlet
Fraunhofer laser diffraction set-up

Particle size analysis 25

 Powder technology

Particle size separation

Particle size separation is an operation in which particles of suitable size are selected and
others are rejected because it is too small or too large. The process is important in
1. Classify powders into separate particle size ranges
2. Recover valuable products
3. To prevent environmental pollution
4. Closed-circuit grinding
5. Removal of fine powder to prompt flow
6. Enhance appearance
7. Prevent segregation

Size separation methods

I. Separation by sieving
It is widely used for particle size separation. The principle is the same as for that used
for particle size analysis. However, there may be some differences mainly:
1. The wire mesh used for construction of British standard sieves should be of a uniform
circular cross-section and the mesh should possess an adequate strength to avoid distortion.
Also it should be resistant to chemical action of any material to be sifted.
Brass and bronze are commonly used materials for construction of sieve meshes but stainless
steel is more common and more suitable.
The use sieves for particle size separation require processing of larger amount of powder than
commonly found in particle size analysis. For this reason sieves used for particle size
separation are larger in area than those used for size analysis.
There are several techniques for encouraging particles to separate to size fractions. These
techniques are based on mechanical distribution of the powder bed and include the following:
a. Agitation method
It is a mechanical induced vibration of sieve meshes, which cause the particles to spin and
to pass through a given aperture.
b. Brushing method
A brush is used to reorient particles on the surface and prevent sieve apertures become
blocked.
c. Centrifugal method

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 Powder technology

Mechanical sieves of this type usually use a mechanical cylindrical sieve with a high speed
rotor inside the cylinder so that particles are thrown outwards by centrifugal forces

These methods used powder in dry state, which may lead to difficulties with some materials.
However, wet sieving is more efficient than the equivalent dry process. Particles being
suspended readily and passing easily through the sieve with less blending of the mesh.

Standards for powders based on sieving

These standards are provided in BP and BPC. The BP stated that the degree of
coarseness or fineness of a powder is differentiated and expressed by reference to the nominal
mesh aperture size of the sieves used. Five grades are specified and defined by BP as
following:

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Description of the Coarsest sieve diameter (µm) Sieve diameter through which
powder grade all particles pass no more than 40% must pass
Coarse 1700 355
Moderately coarse 710 250
Moderately fine 355 180
Fine 180 -
Very fine 125 -

BPC defined another fraction known as ultra-fine powder. In this case it is required that the
maximum diameter of at least 90% of the particles must be no grater than 5 µm and that
non of the particles should have a diameter greater than 50 µm.

II. Separation by fluid classification

Size separation by sedimentation utilizes the differences in settling velocities of
particles with different diameters and this can be related according to stocke’s equation.

Sedimentation methods
1. Sedimentation tank
A suspension of solid in liquid (usually water) is placed in a tank and allowed to stand
for suitable time. The upper layer is then removed giving a single separation, or a suspension
may be collected as a number of fraction by arranging for a pump inlet just below the surface.
The suspension pumped out will then contain successively coarser particles.
Disadvantages
a. It is a batch process
b. Does not give a clear split of particle sizes

2. Continuous sedimentation tank

A tank arranged with inlet and outlet pipes. Particles entering the tank will be acted
upon by a force that can be divided into two component: horizontal component due to flow of
liquid that carries the particles forward and vertical component due to gravity, which cause
the particles to fall down toward the bottom of the tank. So the particles will settle down to
the bottom of the tank at a point that depends on the particle size.

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 Powder technology

Inlet Outlet

Advantages
a. It is a simple and inexpensive process
b. It works in a continuous way
c. It gives a clean separation of particles into many size fractions

III Elutriation
Elutriation is a process of fractionation of fine particles according to their size by
manipulating them in a moving fluid. The class of instruments that fractionate fine particles
according to their size by manipulating them in a moving fluid is called elutriators.

1. Cyclone separator
Cyclone can be used with a liquid suspension of solids but the most common
application is with suspension of a solid in gas. It consists of a cylindrical vessel with a
conical base. The fluid is introduced tangentially at a fairly high velocity, so the fluid stream
is made to spiral downward through the cyclone body until it can reverse its flow and leave
through a pipe known as vortex finder.
The rotary flow within the cyclone causes the particles to be acted on by a centrifugal forces,
particles will be fractionated into two fractions, larger than the cut size and smaller than the
cut size. Particles larger than the cut size being thrown out to the walls then falling to the
conical base and out through the solid discharge.

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 Powder technology

Vortex finder Fluid outlet

Tangential inlet

Solids outlet
Cut size
It is defined as the size of the particles remaining in the elutriator and determined by
cyclone size and velocity of the fluid stream. Cyclone can be used to separate all particles or
to remove only coarse particles and allow fine particles to be carried out with the fluid.

III. Gravity elutriator

It is a procedure in which the fluid moves in a direction opposite to sedimentation
movement. Separation by this method depends on the velocity of the fluid and is independent
on time. The apparatus consists simply of a vertical column with an inlet near the bottom for
the suspension, an outlet at the base for coarse particles and an overflow near the top for fluid
and fine particles.
As fluid pass upward through the column the velocity of the moving fluid can be adjusted to
move all fine particles below the cut size from the elutriator body.

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 Powder technology

Fluid and fine particles

Cut size

Suspension

coarse particles
One column will give a single separation into two fractions, if more than one fraction is
required a number of tubes of increasing area of cross-section can be connected in series.
With the same overall flow rate the velocity will decrease in succeeding tubes as the cross-
sectional area increases giving a number of fractions.

(4)

(1) (2) (3)

Advantages
1. The process is continuous
2. The separation is quicker than sedimentation
3. As many stages can be used as necessary

Particle size separation 31

 Powder technology

Powder properties

Particle properties
The presence of molecular forces produce tendency for solid particles to stick to
themselves and to other surfaces. Adhesion and cohesion are two parts of the same
phenomenon. Cohesion occurs between like surfaces such as component particles of the same
bulk solid whereas adhesion occurs between two unlike surfaces e.g. between a particle and a
hopper wall.
Cohesion forces acting between particles are composed mainly from short range non specific
van der waals forces which increases as particle size decreases and vary with change in
humidity. Other attractive forces may be produced by surface tensional forces between
adsorbed liquid layers at the particle surface and electrostatic forces arising from contact or
frictional charging.
Cohesion provides a useful method of characterizing the frictional forces acting within a
powder bed to prevent a powder flow.

Measurement of adhesion/cohesion properties

Since it is difficult to measure the cohesion forces exist between individual particles,
cohesion is usually defined as the stress necessary to shear a bed of powder under conditions
of zero normal load. However, it is more usual to characterize adhesion/cohesion in a bed of
powder as following:

Shear cell (shearing strength)

The powder is packed carefully into two segments and a lid is placed within the top
segment. This led can be loaded normally with varying loads, then the force required to shear
the bed can be measured. The shear stress can be found by dividing this force by the cross
sectional area of the bed.
normal load
movable upper half
shearing
force fixed lower half
shear plane

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 Powder technology

The load is plotted against the value of shear stress. The shear stress at zero normal load is
equal to the cohesion of the powder.

Shear stress

normal load

Tensile strength
It is a force per unit area required to split the powder bed in tension. To study the tensile
strength the powder is packed into a split plate, one half of which is fixed and the other half is
free to move by means of small wheels or ball bearing which run in grooves in a table.
The table is then tilted toward the vertical until the angle is reached at which the powder
cohesion is overcome and the mobile half breaks away. The tensile strength then can be
determined from the following equation:

static half plate

mobile half plate

tilt angle

Powder properties 33
 Powder technology

t = (M sin /A) x 105 Pa

Where
M = mass of the mobile + powder
 = angle of the tilt table
A= cross-sectional area of the powder bed

Some factors affecting the cohesion of powder

1. Particle size
Since cohesion is a surface effect fine powders are usually more cohesive than coarser
ones.
2. Particle density
Since particles flow under influence of gravity, dense particles are generally less
cohesive than the lighter ones
3. Nature of the surface
The surface of any particle is associated with surface free energy. The surface free
energy is reduced by absorption of gas and water vapour

Powder Flowability
It is the ability of the powder to flow in a desired manner in a specific piece of equipment.
Powder flow is a complex because it is a multi-dimentional and depends on many powder
characteristics. It is known that powder flowability is a combination of material physical
properties that affect material flow and the equipment used for handling, storing or processing of
the material.
Powder flow and powder flow properties
Powder flow is the ability of the powder to flow in a desired manner in a specific piece of
equipment, whereas, powder flow properties is the specific bulk characteristics and properties of
the powder that affect flow, e;g; density (compressibility), cohesion and wall friction.
In pharmaceutical industry flowability is a factor for several processes, which include powder
transfer, storage, tabletting, blending and fluidization.

Powder properties 34
 Powder technology

Angle of repose
It is well realized that a particle begins to slide when the angle of inclination is large
enough to overcome frictional forces. On the other hand particles in motion will stop sliding
when the angle of inclination is below that required to overcome adhesion/cohesion.
In a similar way, particles composing a conical heap of powder on a horizontal surface will
slip and roll over each other until the gravitational force balance the intermolecular forces.
The sides of heap will then form an angle with the horizontal axis, which is known as the
angle of repose.
When the angle is high the cohesive forces is high and vice versa. In general if the angle
exceeds 50° the powder will not flow satisfactory while materials having values near 25° flow
easily and will.

Determination of the angle of repose

The simplest way to determine the angle of repose is to allow the powder to flow
through a funnel or orifice on a horizontal surface beneath. The angle of the conical heap so
formed can be determined from a simple geometry.
Disadvantages
1. suitable for free flowing particles only
2. Does not give reproducible results since the cone formed is distorted by the impact of the
falling powder.

To overcome those drawbacks other methods are designed which include:

The first method is to fill the powder into an open-ended cylinder with the bottom resting on
the horizontal surface. On withdrawing the cylinder vertically the powder will form a heap
from which the angle of repose can be determined.
On opening the sliding shutter the powder in the container flows out via the funnel except for
the conical heap remaining on the circular platform. This method avoid cone distortion due to
falling powder.

Powder properties 35
 Powder technology

Step 2
Open-ended cylinder
Step 1

powder
Powder heap

Another method was designed as show below.

Powder circular platform

Step1 step2

Sliding shutter

Bulk density and particle density

The bulk density of the powder bed is the weight of the powder comprising it divided by
the whole volume of the bed.
The particle density is the weight of the particles divided by its volume. It is always
greater than the bulk density.
The Porosity is the fraction of the powder bed that consist of void space. It is related to
bulk density and particle density by this expression

Porosity = 1 –bulk density/particle density

The packing fraction it is the fractional solid content and equal

Packing fraction = bulk density/true density

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 Powder technology

Bulk and tapped density measurement

The bulk density often is the bulk density of the powder “as poured” or as passively filled
into a measuring vessel. The tapped density is a limiting density attained after “tapping
down,” usually in a device that lifts and drops a volumetric measuring cylinder containing
the powder a fixed distance. Thus, it is essential in reporting bulk density to specify how
the determination was made. Because the interparticulate interactions that influence the
bulking properties of a powder are also the interactions that interfere with powder flow, a
comparison of the bulk and tapped densities can give a measure of the relative
importance of these interactions in a given powder
Bulk density is dependent on the particle packing and changes as the powder consolidates. A
consolidated powder bed is likely to have greater arch strength than a less consolidated
powder and may therefore be more resistant to powder flow. The powder consolidation can be
used as an indirect method of quantifying powder flow.
A mechanical tapping device, which consists of a measuring cylinder mechanically tapped by
means of constant velocity rotating cam, is used to measure the tapped density.
The initial bulk density D0 and the final bulk density (tapped density) Df can be used to
predict powder flow properties through determination of % compressibility

% Compressibility (Carr index) = (Df - D0/ Df) x 100

As percentage compressibility decreased powder flow increase
Spherical monosized particles quickly attain its most stable arrangement and back down
rapidly. For non-spherical particles a longer tapping period is required which mainly due to:
1. Arches and bridges formed need more time to breakdown
2. Smaller particles have to move to the voids between large particles which need time

Hausner ratio:
It is calculated from bulk density and tap density.
Hausner ratio = Tapped density / Bulk density,
Values less then 1.25 indicate good flow (20% Carr index.) and the value greater then 1.25
indicates poor flow (33% Carr index.). If it is between 1.25-1.5 added glident normally to
improve flows.

Powder properties 37
 Powder technology

D0
Df

To motor cam

Tapping machine

Greek Alphabets
 Alpha  Beta
 Gamma  Delta
 Epsilon  Eta
 Theta  Rho
 Lambda  Psi
 Chi  Kappa
 Phi  Pi
 Sigma  Omega
 Mu  Nu

Systeme Internationale (SI) Prefixes

1018 exa (E) 10-18 atto (a)
1015 peta (P) 10-15 fem’o (f)
1012 tera (T) 10-12 pico (p)
109 giga (G) 10-9 nano (n)
106 mega (M) 10-6 micro (µ)
103 Kilo (K) 10-3 milli (m)
102 hecto (h) 10-2 centi (c)
101 deca (da) 10-1 deci (d)

Powder properties 38