SIZE REDUCTION

By
Dr. Ramanjireddy Tatiparthi
JIMMA UNIVERSITY

1
 INTRODUCTION
Size reduction is the process of reducing the particle size of
a substance to a finer state of subdivision to smaller pieces
to coarse particles or to powder.
Size reduction process is also referred to as comminution
and grinding. When the particle size of solids is reduced
by mechanical means it is known as milling.
Raw materials often occur in sizes that are too large to be
used and, therefore, they must be reduced in size.
The size reduction operation divided into two major
categories depending on whether the material is a solid or
a liquid.
If the material is solid, the process is called grinding and
cutting, if it is liquid, emulsification or atomization. 2
 Objectives of Size Reduction
1. Size reduction increases the surface area of drugs that helps in rapid
solubilization.
2. The extraction from animal glands such as liver and pancreas
facilitated
3. To increase the therapeutic effectiveness by reducing the particle
size e.g., griseofulvin.
4. Crystalline drugs can be powdered before mixing them with
excipients.
5. The stability of emulsions is increased by decreasing the size of the
oil globules.
6. Particle size plays an important role in the case of suspensions.
7. The physical appearance of ointments, pastes and creams can be
improved by reducing its particle size.

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 Factors Affecting Size Reduction
1. Hardness:
Hardness is a surface property of the material, a material to be very
hard, but if it is brittle also then size reduction may present no
special problems.
An arbitrary scale of hardness has been devised known as Moh’s
Scale; a series of mineral substances has been given hardness
numbers between 1 and 10, ranging from graphite to diamond.
Up to 3 are known as soft and can be marked with the fingernail.
Above 7 are hard and cannot be marked with a good pen knife
blade, while those between are described as intermediate.
In general, the harder the material the more difficult it is to reduce in
size.

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2. Toughness:
Toughness of a material is sometimes more important than hardness, a soft but
tough material may present more problems in size reduction than a hard but
brittle substance for example it is difficult to break rubber than a stick of
blackboard chalk.
Toughness is encountered in many pharmaceutical materials, particularly in
fibrous drugs, and is often related to moisture content.
For some materials, toughness can be reduced by treating the material with a
liquefied gas such as liquid nitrogen, substances can be cooled to temperatures
lower than -100 to -150○C.
The method has additional advantages, in that there is a reduction in the
decomposition of thermolabile materials, in the loss of volatile materials, in the
oxidation of constituents, and in the risk of explosion.
This procedure is little used, as it is expensive but also due to engineering
problems: for example, the metals of the machinery also become brittle at such
low temperatures, and normal lubricants solidify.
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3. Abrasiveness:
Abrasiveness is a property of hard materials and may limit the type of
machinery that can be used. During the grinding of some very
abrasive substances the final powder may be contaminated with
more than 0.1 percent of metal worn from the grinding mill.
4. Stickiness:
Stickiness is a property that causes considerable difficulty in size
reduction, for material may adhere to the grinding surfaces, or the
meshes of the screen may become choked.
If the method used for size reduction produces heat then substances
that are gummy or resinous may be troublesome to the size
reduction process.
Sometimes the addition of inert substances may be of assistance such
as kaolin to sulphur. Since the material acts as a lubricant and
lowers the efficiency of the grinding surfaces.
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5. Softening temperature:
During size reduction process sometimes heat is generated which
may cause some substances to soften, and the temperature at
which this occurs can be important.
Waxy substances, such as stearic acid, or drugs containing oils or
fats are examples that may be affected.
Some methods can be used to overcome this like cooling the mill,
either by a water jacket or by passing a stream of air through
the equipment. Another alternative is to use liquid nitrogen.
6. Material structure:
Some substances are homogeneous in character, but the majority
show some special structure, for example, mineral substances
may have lines of weakness along which the materials splits to
form flake-like particles, while vegetable drugs have a cellular
structure often leading to long fibrous particles.
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7. Moisture content:
Moisture content influences a number of properties that can affect size
reduction, for example, hardness, toughness or stickiness. In general
materials should be dry or wet and not merely damp. Usually, less than
5 percent of moisture is suitable if the substance is to be ground dry or
more than 50 if it is being subjected to wet grinding
8. Physiological effect:
Some substances are very potent and small amounts of dust have an effect
on the operators. To avoid this dust, enclose mills must be used,
systems that can extract air are also desirable, and wet grinding also, if
possible, as it eliminates the problem entirely.
9. Purity required:
Certain types of size reduction apparatus cause the grinding surfaces to
wear, and such methods must be avoided if a high degree of purity of
product is needed. Similarly, some machines will be unsuitable if
cleaning between batches of different materials is difficult.

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10. Ratio of feed size to product ratio:
Machines that produce a fine may be necessary to
carry out the size reduction process in several
stages with different equipment, for example,
preliminary crushing, followed by coarse grinding
and then fine grinding.
11. Bulk density:
The capacity of most batch mills depend on volume,
whereas processes usually demand solid materials
by weight. Hence, all other factors being equal,
the output of the machine is related to the bulk
density of the substance.
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 Mechanism and Principles of Size Reduction
The mechanism of size reduction may vary with the nature of the material
and each drug may require separate treatment. Fracture occurs
preferentially along lines of weakness. Fresh surfaces may be created or
existing cracks and fissures may be opened up, the former requiring
much more energy.
Crack propagation and toughness
1. Size reduction is caried out by a process of propagation, where by
localized stresses produce strains in the particles
2. Strains energy in specific regions according to griffith’s theory,
the strain multiplier σk= 1+2(L/2r) where, L= length of crack propagation ,
r= radius of the crack
3. Not all the material exhibit this type of brittle behavior and resist the
fracture at much larger stress
4. The tough material under plastic flow, the strain relaxation is with out
crack propagation, material slip over one another deformation
Modification of griffith’s theory : σ =Ep/C where Ep = energy required to form unit area of double
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surface
 Laws governing energy and power
requirement of Size Reduction process
Grinding is a very inefficient process and it is important to use
energy as efficiently as possible. Unfortunately, it is not easy to
calculate the minimum energy required for a given reduction
process, but some theories have been advanced which are useful.
A number of theories have been advanced to predict the energy
requirements of a size reduction process, but none give accurate
results.
These theories depend upon the basic assumption that the energy
required to produce a change dL in a particle of a typical size
dimension L is a simple power function of L: dE/dL= KLn
Where dE is the differential energy required, dL is the change in a
typical dimension; L is the magnitude of a typical length
dimension and K, n, are constants.
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 Kick’s theory
Kick assumed that the energy required to reduce a material in size
was directly proportional to the size reduction ratio dL/L. This
implies that n in equation is equal to -1. If K = KKfc
Where KK is called Kick's constant and fc is called the crushing
strength of the material, we have:
dE/dL= KK fc L-1
Which, on integration gives: E= KK fc loge (L1/L2)
This Equation is a statement of Kick's Law. It implies that the specific
energy required to crush a material, for example from 10 cm down
to 5 cm, is the same as the energy required to crush the same
material from 5 mm to 2.5 mm.

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 Rittinger’s theory
Rittinger assumed that the energy required for size reduction is directly
proportional, not to the change in length dimensions, but to the change in
surface area. This leads to a value of -2 for “n” in equation. as area is
proportional to length squared. If we put:
K= KRfc and so dE/dL= KR fc L-2
Where, KR is called Rittinger's constant, and integrate the resulting form of eqn, we
obtain:
E= KR fc (1/L2– 1/L1)
This equation is known as Rittinger's Law. As the specific surface of a particle, the
surface area per unit mass, is proportional to 1/L, this equation postulates that
the energy required to reduce L for a mass of particles from 10 cm to 5 cm
would be the same as that required to reduce, for example, the same mass of 5
mm particles down to 4.7 mm. This is a very much smaller reduction, in terms
of energy per unit mass for the smaller particles, than that predicted by Kick's
Law.
It has been found, experimentally, that for the grinding of coarse particles in which
the increase in surface area per unit mass is relatively small, Kick's Law is a
reasonable approximation. For the size reduction of fine powders, on the other
hand, in which large areas of new surface are being created, Rittinger's Law 13fits
the experimental data better
 Mechanism of Size Reduction
Cutting – here the material is cut by means of a sharp blade or
blades.
Compression– in this method, the material is crushed by application
of pressure.
Impact– impact occurs when the material is more or less stationary
and is hit by an object moving at high speed or when the moving
particle strikes a stationary surface. In either case, the material
shatters to smaller pieces. Usually both will take place, since the
substance is hit by a moving hammer and the particles formed are
then thrown against the casing of the machine.
Attrition– in attrition, 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.

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 Methods of size reduction
Cutting and compression have limited uses in
Pharmaceutical practice, impact and attrition are used
much more widely, both separately and in combination,
and there is a great variety in each type. The machines
used for size reduction are often termed as mills.
Grinding Equipment
Grinding equipment can be divided into two classes -
crushers and grinders. In the first class the major action is
compressive, whereas grinders combine shear and impact
with compressive forces.

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 Equipments based on the mechanism of Cutting
Cutting machinery is simple, consisting of rotating knives in various
arrangements. The knives are kept sharp so that they cut rather than tear.
An example is the bowl chopper in which a flat bowl containing the
material revolves beneath a vertical rotating cutting knife.
Crushers: Jaw and gyratory crushers are heavy equipment and are not used
extensively in the food industry. In a jaw crusher, the material is fed in
between two heavy jaws, one fixed and the other reciprocating, so as to
work the material down into a narrower and narrower space, crushing it
as it goes.
The gyrator crusher consists of a truncated conical casing, inside which a
crushing head rotates eccentrically. The crushing head is shaped as an
inverted cone and the material being crushed is trapped between the
outer fixed, and the inner gyrating, cones, and it is again forced into a
narrower and narrower space during which time it is crushed. Jaw and
gyratory crusher actions are illustrated in Figure 1(a)and (b).

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Crushing rolls consist of two horizontal heavy
cylinders, mounted parallel to each other and close
together.
They rotate in opposite directions and the material to be
crushed is trapped and nipped between them being
crushed as it passes through.
A major application is in the cane sugar industry, where
several stages of rolls are used to crush the cane.

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 Equipments based on the mechanism of Impact
1. Hammer mills:
In a hammer mill, swinging hammer heads are attached to a rotor that
rotates at high speed inside a hardened casing. The principle is
illustrated in Figure.
The hammer mill consists of a steel casing in which a central shaft is
enclosed to which a number of swinging hammers are attached.
When the shaft is rotated the hammers swing out to a radial
position. On the lower part of the casing a screen of desired size is
fitted which can be easily replaced according to the particle size
required.
The material is crushed and pulverized between the hammers and the
casing and remains in the mill until it is fine enough to pass
through a screen which forms the bottom of the casing..

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Both brittle and fibrous
materials can be handled
in hammer mills. The
hammer mills are
available in various
designs and shapes. In
pharmaceutical industry
they are used for grinding
dry materials, wet filter
cakes, ointments and
slurries

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Advantages:
1. It is rapid in action, and is capable of grinding
many different types of materials.
2. They are easy to install and operate, the operation
is continuous.
3. There is little contamination of the product with
metal abraded from the mill as no surface move
against each other.
4. The particle size of the material to be reduced can
be easily controlled by changing the speed of the
rotor, hammer type, shape and size of the screen

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Disadvantages:
1. The high speed of operation causes generation of heat that
may affect thermolabile materials or drugs containing
gum, fat or resin. The mill may be water-cooled to reduce
this heat damage.
2. The hammer mill is capable of producing intermediate
grades of powder from almost any substance, apart from
sticky materials that choke the screen.
3. Applications include the powdering of barks, leaves, roots,
crystals and filter cakes. With cutting edges to the
hammers, the method has proved to be especially useful
for granulation, the damp masses being cut to granules by
the hammers when they are found to produce greater
uniformity than is obtained by sieve granulation.
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2. Plate mills:
In plate mills the material is fed between two circular plates, one of
them fixed and the other rotating. The feed comes in near the
axis of rotation and is sheared and crushed as it makes its way to
the edge of the plates; see Figure.
The plates can be mounted horizontally as in the traditional
Buhrstone used for grinding corn, which has a fluted surface on
the plates. The plates can be mounted vertically also.
Developments of the plate mill have led to the colloid mill, which
uses very fine clearances and very high speeds to produce
particles of colloidal dimensions.

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 Equipments based on the mechanism of Attrition
Size reduction by attrition can be effected in the laboratory by using pestle
and mortar or, if a small-scale mechanical method is required, the roller
mill can be used.
1. Roller mills:
Roller mills are similar to roller crushers, but they have smooth or finely
fluted rolls, and rotate at differential speeds.
The roller mills use the principles of attrition for the size reduction of solids
in suspensions, pastes, or ointments.
Two or three rolls, usually in metal or in porcelain, are mounted horizontally
with a very small, but adjustable, gap between.
The rolls rotate at different speeds, so that the material is sheared as it passes
through the gap and is transferred from the slower to the faster roll, from
which it is removed by means of a scraper. The method is very effective
for size reducing and dispersing solids in semi-solid media.

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Triple Roller mill:
Various types of roller mills consisting of one or more
rollers are commonly used but triple roller mill is
preferred.
It is fitted with three rollers that are composed of a hard
abrasion-resistant material. They are fitted in such a
way that they come in close contact with each other
and rotate at different speeds.
The material that come, in-between the rollers is crushed
and reduced in particle size. The reduction in particle
size depends on the gap between the rollers and
difference in their speeds.

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In figure 3, the material is allowed to pass through hopper A, in-between the rollers
B and C where it is reduced in size. Then the material is passed between the
rollers C and D where it is further reduced in size and a smooth mixture is
obtained. The gap between rollers C and D is usually less than the gap between
B and C, after passing the material between rollers C and D the smooth ended
material is continuously removed from roller D by means of scraper E, from
where it is collected in a receiver.
On large scale, mechanical ointment roller mills are used to obtain an ointment of
smooth and uniform texture. The performed coarse ointments are forced to pass
through moving stainless steel rollers where it is reduced in particle size and a
smooth product which is uniform in composition and texture is obtained. For
small scale work, small ointment mills are available.

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 Equipments based on the Combined Impact and Attrition
1. Colloid mill:
Colloid mill works on the principle of shearing. The colloid mill is useful
for milling, dispersing, homogenizing and breaking down of
agglomerates in the manufacture of pastes, emulsions, coatings,
ointments, creams, pulps, grease etc.
The main function of the colloid mill is to ensure a breakdown of
agglomerates or in the case of emulsions to produce droplets of fine size
around 1 micron.
The material to be processed is fed by gravity to the hopper or pumped so as
to pass between the rotor and stator elements where it is subjected to
high shearing and hydraulic forces as illustrated in figure 4(a) and (b).
Material is discharged through a hopper whereby it can be recirculated
for a second pass.
For materials having higher solid and fiber contents conical grooved discs
are preferred.
Cooling and heating jacket arrangements are provided as a standard feature
on both these mills. 26
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Rotational speed of the rotor varies from 3,000-20,000r.p.m. with the
spacing between the rotor and stator capable of very fine adjustment
varying from 0.001 inch to 0.005 inch depending on the size of the
equipment.
In these mills almost all the energy supplied is converted to heat and the
shear forces can increase the temperature of the product. Hence most
colloid mills are fitted with water jackets and it is also necessary to cool
the material before and after passing through the mill.
In the Premier colloid mill, intense shearing action is produced between the
rotor running at several thousand rpm with its working surface in close
proximity to the stator. Rotor runs at 9000 r.p.m. and has an output of
40-60 gallons depending on the viscosity of the liquid. The gap between
the two surfaces is adjustable from 0.3-0.002inch.
Colloid Mills are used in the production of ointment, cream, gels and high
viscous fluids for grinding, dispersing and homogenizing in one
operation.

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Advantages
1. Extremely fine particle distribution through optimal
shear force
2. High capacity with minimal space requirements.
3. Rapid handling and easy cleaning.
4. Virtually highly flexible homogenization system

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2. Ball mill:
Ball mill is a type of crusher, is a cylindrical device used to grind materials
like ores, chemicals, ceramics and paints.
Ball mills rotate around a horizontal axis, partially filled with the material to
be ground plus the grinding medium.
Different materials are used for media, including ceramic balls, flint pebbles
and stainless steel balls. An internal cascading effect reduces the material
to a fine powder.
Large to medium ball mills are mechanically rotated on their axis, but small
ones normally consist of a cylindrical capped container that sits on two
drive shafts.
A rock tumbler functions on the same principle. High quality ball mills are
potentially expensive and can grind mixture particles to as small as
0.0001 mm, enormously increasing surface area and reaction rates.

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The material to be ground is added so that it is slightly
more than fills the voids between the pellets.
The shell is rotated at a speed which will cause the pellets
to cascade, thus reducing particle sizes by impact.
Common in some applications are stainless steel balls.
While usually very effective due to their high density
and low contamination of the material being processed.
Ball mills are very effective for grinding smooth, aqueous
or oily dispersions by wet grinding since it will give
particles of 10 microns or less.

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Advantages:
1. Ball mill is capable of grinding a wide variety of materials of differing
character and of different degrees of hardness.
2. It can be used in a completely enclosed form, which makes it especially
suitable for use with toxic materials.
3. It can produce very fine powders.
4. It can be used for continuous operation, and a classifier can be used in
conjunction with the mill, so that particles of suitable size are removed while
oversize particles are returned.
5. It is equally suitable for wet or dry grinding processes.
Disadvantages
6. Wear occurs, principally from the balls, but partially from the casing and this
may result in the product being contaminated, with abrasive materials this may
exceed 0.1 percent, but even ordinary substances may be contaminated with
0.03 percent metal after grinding.
2. Soft or sticky materials may cause problems by caking on the sides of the mill.
3. The ball mill is very noisy machine, particularly if the casing is of metal.

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3. Fluid energy mill:
It consists of a loop of a pipe, which has a diameter of 20 to 200
mm, depending on the overall height of the loop which may
be up to about 2 meters, a fluid, usually air, is injected at high
pressure through nozzle sat the bottom of the loop, giving rise
to a high velocity circulation in a very turbulent condition.
Solids are introduced into the stream and, as a result of the high
degree of turbulence, impact and attritional forces occur
between the particles. A classifier is incorporated in the
system, so that particles are retained until sufficiently fine.
The feed to the mill needs to be pre-treated to reduce the
particles size to the order of 100 mesh, enabling the process
to yield a product as small as 5 micrometers or less.

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Advantages:
1. The particle size of the product is smaller than that produced by any
other method of size reduction.
2. Expansion of gases at the nozzles leads to cooling, counter acting the
usual frictional heat which can affect heat-sensitive materials.
3. Since the size reduction is by inter-particulate attrition there is little or
no abrasion of the mill and so virtually no contamination of the
product.
4. For special cases with very sensitive materials it is possible to use inert
gases.
5. Having a classifier as an integral part of the system permits close
control of particle size and of particle size distribution.
6. The method is used where especially fine powders are required, and
antibiotics, sulphonamides and vitamins are typical examples.

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36
 Factors influencing choice of Size Reduction machinery
1. Nature of the raw material:
Drugs must be thoroughly dried before they are subjected to size
reduction. Drugs like belladonna, gentian, liquorice and squill are
returned to the drying rooms to the drying rooms after they have
been partially comminuted, as they rapidly absorb moisture from
the atmosphere and as the moisture may not be removed from all
parts of the drug during the initial drying stage.
In the case of water insoluble substances, wet grinding of the
material can be done. For the preparation of aqueous dispersions
of drugs this method is very effective since deflocculating agents
may be included to prevent agglomeration of the particles.
Substances that are hygroscopic or volatile or very poisonous or that
need-prolonged trituration are more easily prepared in closed
porcelain ball mills.

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Fibrous material seed tearing apart of the fibers and
this can be achieved in high-speed impact mills.
Substances of a resinous or oily nature shall not be
subjected to heavy pressures or much heat as a
pasty mass may result. Hence, a ball mill will not
be suitable and they are better grounded in a
micronizer or a hammer mill.
The replacement of air by an inert gas is necessary
when grinding readily oxidizable materials and
ball mills and high-speed impact mills are
generally used in this way.
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2. Nature of the product:
A powdered drug produced in a ball mill differs from the product in a
micronizer or a disintegrator even though both powders may be
screened to the same fineness.
Differences exist in the shape of the particles, their toughness and
their internal pore structure. Powder obtained from grinding mills
like ball mill is more compact and less porous than that obtained
in high speed impact mills like a disintegrator.
For the grinding of a sterile material under aseptic conditions, a mill
is required that can be easily sterilized and sealed to prevent
contamination during the grinding operation. A batch operation
porcelain ball mill is most suitable for this purpose.
When iron and copper contamination of pharmaceutical products is
to be avoided stainless steel or ceramic material may be used for
the surfaces of a mill coming into contact with the drug.

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3. Degree of comminution required:
The degree of comminution of materials varies according to the
purpose for which they are required. For the preparation of
galenicals, the size of the vegetable drug powder employed for
extraction varies from coarse to fine powder.
Tincture preparation requires bruised to moderately coarse powders.
For percolation, drug powders should not contain a large proportions
of fines to avoid uneven extraction.
Coarse to moderately coarse powder, with a minimum of fine powder,
are all most easily obtained by using high speed mills of the impact
type. Materials such as cascara, liquorice, belladonna leaf and root
and ginger are all easily broken down in such mills.

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Penicillin in a medium of aluminium monostearte
and arachis oil appears to be most effective when
90 % of the particles are smaller than 5
micrometers. The relatively insoluble
sulphonamides attain their maximum
antibacterial activity at crystal sizes of about 1
micrometer or below. For insufflations the drug
should be smaller than about 5 micrometers.

41
 Pharmaceutical Applications of Size Reduction
1. Size reduction increases the surface area per unit weight
also known as the specific surface area. Thus, a given
weight of finely powdered medicinal compound dissolves
in a shorter time than does the same weight of a coarse
powder. For example, the control of fineness of
griseofulvin led to an oral dosage regimen half that of the
originally marketed product.
2. Particle size control influences the duration of adequate
serum concentration, rheology, and product syringeability
of a suspension of penicillin G procaine for intramuscular
injection.
3. The rectal absorption of aspirin from a theobroma oil
suppository is related to particle size. 42
4. There is an increase in antiseptic action for
calomel ointment when the particle size of
calomel is reduced.
5. The size of particles used in inhalation aerosols
determines the position and retention of the
particles in the broncho-pulmonary system.
6. Size may affect texture, taste and rheology of oral
suspensions in addition to absorption.
7. The time required for dissolution of solid
chemicals in the preparation of solutions is
shortened by the use of smaller particles.
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