Definition:

Size reduction is a process of reducing large solid unit masses vegetables or chemical substances
into small unit masses, coarse particles or fine particles. Size reduction is commonly employed in
pharmaceutical industries.

Size Reduction is a pharmaceutical process where bigger drug particles are converted into
smaller drug particle as per requirement.

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. The size reduction operation
can be 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.
Advantages/Objective/Importance of size reduction:
1. Size reduction leads to increase of surface area & viscocity.
2. Pharmaceutical capsules, insufflations (i.e. powders inhaled directly into the lungs),
suppositories and ointments require particles size to be below 60 mm size.
3. To increase the therapeutic effectiveness of certain drugs by reducing the particle size.
4. Size reduction produces particles in narrow size range. Mixing of powders with narrow size
range is easier.
5. The mixing of several solid ingredients is easier and more uniform if the ingredients are
reduced to same particle size.
6. Pharmaceutical suspensions require finer particle size. It reduces rate of sedimentation.
7. The stability of emulsions is increased by decreasing the size of the oil globules.
8. All the ophthalmic preparations and preparations meant for external application to the skin
must be free from gritty particles to avoid irritation of the area to which they are applied.
9. The rate of absorption of a drug depends on the dosage form, route of administration and
particle size. The smaller the particle size, quicker and greater will be rate of absorption. Hence
size reduction ensures good bioavailability e.g Griseofulvin.
10. The physical appearance of ointments, pastes and creams can be improved by reducing its
particle size.
11. To increase the rate of a solution: Size reduction reduces particle size and increases effective
surface area which in turn increases the rate of solution.
12. To increase the rate of extraction: Rate of extraction is directly proportional to Size
reduction. Smaller particle size allows faster penetration of menstruum and hence fastens the
extraction process.
13. Drying: Reduction in particle size increases effective surface area and fastens the process of
drying.
14. To facilitate Filtration: Rate of filtration depends upon the size of particles to be separated.

Disadvantages of Size reduction:

1. Dru degradation.
2. Contamination from reductive machineries /equipment’s.
3. Poor mixing of some drug.
Mechanisms of Size Reduction:
Size reduction is the process of conversion of bigger particles into smaller particles, which is
achieved by following mechanism---
1. Cutting or shear.
2. Compression
3. Impact
4. Attrition
5. Combined impact and attrition.
1) Cutting or shear:
 The material is size reduced when it comes between sharp edges of the blades. e.g Cutter
Mill.

2) Compression:
 The material is size reduced by crushing when comes between a stationary platform and a
moving heavy platform. e.g. Mortar and pestle, Roller Mill.
3) Impact:
 The material is size reduced when hit by a moving platform or material at a high speed.
e.g Dis-integrator, hammer mill.
4) Attrition:
 The material is size reduced by application of pressure and the shear force generated
when it comes between the platforms moving relative to each other. e.g Mortar and pestle
and Roller mill.
5) Combined Impact and Attrition:
 The material is size reduced by combined action of impact and attrition to get better
results. e.g. Ball Mill, Fluid energy mill.

Factors affecting size reduction:

1. Hardness - It is easier to break soft material than hard materials. Ex: For iodine hammer
mill is used.
2. Fibrous - These are tough in nature. A soft, tough material has more difficulty than a
hard, brittle substance. Ex: Rauwlfia, Ginger. Here cutters can be used.
3. Friable- These tend to fracture along well-defined planes. Brittle substances can be easily
converted into fine particles. Ex: Sucrose. Mechanism used is attrition, impact and
pressure.
4. Brittle- Brittle substances can be easily converted into fine particles
5. Elastic / Sticky - Become soft during milling. Ex: synthetic gums, waxes, resins. Low
melting substances should be chilled before milling. These are milled using hammer,
colloid or fluid energy mill.
6. Melting point - Waxy substances, fats and oils are softened during size reduction due to
heat generated. This is avoided by cooling the mill and the substance.
7. Hygroscopic - Certain substances absorb moisture content rapidly. This wet mass
hampers the milling process. Ex: Potassium carbonate. Closed system such as porcelain
ball mill is used.
8. Solvated- Hydrates liberate water during milling, causes clogging of mill. Ex: sodium
sulphate.
9. Thermolability- Certain Substances are degraded by hydrolysis and oxidation, due to
moisture and atmospheric oxygen. Heat produced on milling enhances these reactions.
Closed system is used here with an inert atmosphere of CO2 and N. Vitamins and
antibiotics are milled using fluid energy and ball mills.
Other Factors affecting size reduction
1. Purity required - The size reduction of such hard substances leads to the abrasive wear
of milling parts, causing contamination. Such mills are to be avoided. The mills should be
thoroughly cleansed between different batches.
2. Flammability - Under certain conditions fine dust such as dextrin, starch, sulphur are
potential explosive mixtures. All electrical switches should be explosive proof and mill
should be well grounded
3. Particle size - The feed should be of proper size and enter the equipment at a uniform
rate to get a fine powder. Several stages are carried out in size reduction process. Pre-
treatment of fibrous materials with pressure rollers and cutters facilitates further
Comminution.
4. Moisture content- Presence of more than 5 % moisture influences hardness, toughness,
stickiness of substance. In general, materials with moisture content below 5 % are
suitable for dry grinding and above 50 % for wet grinding.
Laws of energy requirement of crushing or grinding
equipments:
A number of theories have been proposed to establish a relationship between energy input and
the degree of size reduction produced----
1. Rittinger’s theory
2. Bond’s theory
3. Kick’s theory
4. Walker’s theory

1.Rittinger’s theory: suggests that energy required in a size reduction process is

proportional to the new surface area produced.

E = KR (Sn-Si)
Where, E = energy required for size reduction
KR = Rittinger’s constant
Si = initial specific surface area
Sn = final specific surface area
Application: It is most applicable in size reducing brittle materials undergoing fine milling
where there is a much larger increase in surface area

2. Bond’s theory: states that the energy used in crack propagation is proportional to the new
crack length produced.

Where, E = energy required f or size reduction

KB = Bond’s work index
di = initial diameter of particles
dn = final diameter of particles
Application: This law is useful in rough mill sizing. The work index is useful in comparing the
efficiency of milling operations.

3.Kick’s theory: states that the energy used in deforming (or fracturing) a set of particles of
equivalent shape is proportional to the ratio of change of size/diameter

Where, E = energy required for size reduction

KK = Kick’s constant
di = initial diameter of particles
dn = final diameter of particles
Application: For crushing of large particles Kick’s theory most useful. It gives reasonably good
results for coarse grinding in which there is a relatively small increase in surface area per unit
mass.

4.Walker Theory: proposed a generalized differential form of the energy-size relationship:

Where E = amount of energy (work done) required to produce a change

D = size of unit mass
d = Diameter of particles.
K = Constant
n = constant
For n =1.0 Walker equation becomes Kick’s theory It is used for coarse particles > 1 um.
n =1.5 Walker equation becomes Bond’s theory. This theory is used when neither Kick’s nor
Rittinger’s law is applicable.
n =2.0 Walker equation becomes Rittinger’s theory Used for fine particles < 1 um size.

Method of size reduction:

Different types of method employed for desired size reduction, which are of following----
1. Crusher (Coarse & Fine particles)
 Jaw Crusher
 Gyratory Crusher
 Crushing Rolls
 Edge Runner Mill
 End runner Mill
2. Grinder (Intermediate & Fine)
 Hammer Mill
 Rolling-Compression Mill (Bowl Mill, Rolling Mill)
 Attrition Mill
 Revolving Mill (Rod, Ball, Pebble, Tube Mills)
3. Ultrafine Grinders
 Hammer Mill with internal classification.
 Fluid energy mill
 Agitator Mill
4. Cutting machine
 Knife Cutter
 Dicers
 Slitter

Hammer Mill:
Principle:
It operates on the principle of impact between rapidly moving hammers mounted on rotor and
the stationary powder material.
Parts:
Consists of a metal casing, enclosing a central shaft, to which 4 or more swinging hammers are
attached. Lower part of casing consists of a screen, through which material can pass and
collected in a suitable receiver.

Construction:
1. The mill consists of a metallic case, rotor, a central shaft with hammers, screen, feed and
outlet.
2. The metallic case contains a rotor at the middle which has attached four to seven
swinging hammers.
3. The motor is moved with help of electricity and speed of which can be controlled with
help of panels.
4. The feed is used to introduce raw material in the mill.
5. The removable screen is attached at the bottom.
6. The product outlet at the bottom is used to collect finished product.

Working:
1. The material to be size reduced is introduced into the mill through the feed.
2. The electrical supply of mill is started after a careful closure of feed.
 3. The central panel with hammers starts rotating at speed.
4. The size reduction takes place when material his hit by swinging hammers and collision
of particles with the stationary metallic wall of the case.
5. The size reduced material falls on the screen at the bottom.
6. The vibrations of mill help in coming out of product through the screen.
7. The screen of desired aperture size can be used as per requirement.
8. This are mainly operated at 1000 to 2500 rpm for the reduction of the large sized particles
High speed rotor uses 10000 rpm speed.

Uses:
1. Brittle material is best fractured by impact from blunt hammers
2. Fibrous material is best reduced by cutting edges
3. It is used to mill dry materials, wet filter press cakes, ointment, slurries etc.

Variants:
 Fitzpatrick comminuting machine - Fitz mill
 Stokes Tornado mill

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 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.
5. As it is a closed system Toxic substances can be ground.

Disadvantages:
1. Heat build up during milling is more, therefore, product degradation is possible.
2. Hammer mills cannot be employed to mill sticky, fibrous and hard materials.
3. The screens may get clogged.

Fluid energy Mill:

Principle:
It operates on the principle of impact and attrition.
Parts:
 Consists of a loop of pipe with diameter 20-200 mm. The overall height of the pipe is 2
m.
 Inlet for feed and a series of nozzles for air, inert gas. Outlet with classifier which
prevents the particles to pass until they become sufficiently fine.

Construction:
1. It consists of a loop of metallic pipe with a diameter of 20 to 200 mm depending on the
height of loop, which may be around 2 m.
2. It has an opening for material feed.
3. The base of the mill has nozzles for inlet of air under pressure.
4. The mill at the top has an opening with a classifier which acts as a product outlet.
5. Most of the time the outlet is connected with Cyclone Separator for size separation of
particles.
Working:
1. The material to be size reduced is entered in the machine through the feed.
2. The nozzles at base introduce the air under pressure at high velocity which pushes the
particles towards the wall.
3. The material moves in an elliptical path creating turbulence.
4. The size reduction takes place due to the impact of particles on the wall and inter-
particulate friction.
5. The smaller particles are carried away with air at the top while the larger particles due to
centrifugal force are throw at the bottom and again get thrown away till becomes small in
size.
6. Other inert gasses can be used as per requirement of material.
7. The expanding and moving of air also cools down the heat generated by the mill.
8. The particles of desired size range get separated by classifier while others continue their
journey with air flow.
9. Fluid energy mill is considered as one of the most efficient mills as it can produce
particles up to 1 to 20-micron size.

Uses:
1. The mill is used to grind heat sensitive material to fine powder
2. The mill is used to grind those drugs in which high degree of purity is required.
3. It is used to reduced particle size of antibiotics, pigments, dyes, cosmetics, vitamins &
food products.

Variants:
Centrifugal impact pulverizer

Advantages:
1. The mill is used to grind the material to fine powder
2. The particle size of powder can be controlled due to the use of a classifier
3. There is no wear of the mill and hence there is no contamination of the product
4. It is useful for grinding heat sensitive substances such as sulphonamides, vitamins and
antibiotics
5. Continuous operation is possible.
Disadvantages:
1. Tendency of forming aggregates or agglomerates after milling
2. Generation of amorphous content due to high energy impact
3. Formation of ultra fine particles
4. High energy consumption
5. Not suitable for sticky products.

Disintegrator:

Principle:
The size reduction is done by impact.

Parts:
Consists of a steel drum enclosing a central shaft, which has a disc to which 4 beaters are fixed.
The side and upper inner surface of drum is rough. Lower part of casing consists of a detachable
screen.
Construction:
1. The mill consists of a metallic body with an inner undulating surface, feed, screen, set of
beaters, rotor, dust bag and a product outlet.
2. The inner surface is undulated which facilitates size reduction.
3. The mill consists beaters attached to a rotor.
4. The rotor moves with help of electricity.
5. The speed of the machine can be adjusted with help of control mechanism.
6. The dust bag is attached to remove dust generated during operation.
7. The base of the body contains a screen, the screens of different aperture size can be
attached to get desired product size.

Working:
1. The material to be size reduced is entered into the machine through the hopper.
2. The electrical supply to the machine is started after a careful closure of the machine feed.
3. The rotors are rotated at desired speed.
4. The size reduction takes place by mechanisms of impact when material falls on the beater
and is thrown on an undulating inner surface, the process repeats.
5. The size reduced material falls on the screen present at the bottom.
6. The dust generated during operation is collected in the dust bag.
7. The vibration of mill helps in moving of product into the outlet.
8. The size reduced material is collected from product outlet.

Uses:
1. To powder all types of drugs including very hard drugs.
2. As application takes place in closed environment useful for potent drugs also.

Advantages:
1. Useful for batch operations.
2. Application of screen ensures the product of desired size range.

Disadvantages:
1. Not suitable for sticky products.
2. Not useful for a continuous process.
3. Produces heat hence not suitable for thermolabile substances.
4. Pretreatment of material is necessary before the operation: Adds to cost of the final
product.
Advances in Size Reduction Technologies:
1. Micron technologies - Micronizing is defined as particles smaller than 20 microns. It
enhances solubility and improves bioavailability, optimizes the formulation of the
product and reduces therapeutic dose. High pressure air / gas are introduced causing
particle collision and micronization.
2. Gran-U-Lizer Technology - It is designed to maximize yield and minimize the size of
particles. In this process there is regrinding of already ground particle, resulting in very
tight particle size.
3. Jet-O-Mizer particle size reduction - This mill is designed with distinct features to
consume less power, provide greater range of output and ensures exceptional finished
product quality. It is efficient in fine grinding and classification, no attritional heat,
adjustable classification zone.
4. Micro fluidizer particle size reduction - The ultra-high shear developed by the micro
fluidizer processor reduces the particle size and high turbulence prevents agglomeration.
This method produces a very stable product with long shelf life.