SIZE REDUCTION& SIZE

SEPARATION

Prepared By
Md. Abdur Rahman
Lecturer, Department of
Pharmacy
Noakhali Science & Technology
University
SIZE REDUCTION
 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, blending, emulsification or atomization.
 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 6 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---
 Cutting or shear.
 Compression
 Impact
 Attrition
 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.

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. For
example--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 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
FOR CRUSHING OR GRINDING
OPERATION

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
 RITTINGER’S THEORY

• 1.Rittinger’s theory: The oldest theory, Von Rittinger(1867), stated

that suggests that energy required in a size reduction process is
proportional to the new surface area produced.

• 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.
 BOND’S THEORY

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.
 KICK’S THEORY

Kik’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.
 WALKER THEORY

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 = Walker constant
• n = constant
 METHOD OF SIZE REDUCTION

1. Crusher (Coarse & Fine particles) 3. Ultrafine Grinders

 Jaw Crusher  Hammer Mill with internal
 Gyratory Crusher classification.
 Crushing Rolls  Fluid energy mill
 Edge Runner Mill  Agitator Mill
 End runner Mill

2. Grinder (Intermediate & Fine) 4. Cutting machine

 Hammer Mill  Knife Cutter
 Rolling-Compression Mill (Bowl Mill,  Dicers
Rolling Mill)  Slitter
 Attrition Mill
 Revolving Mill (Rod, Ball, Pebble, Tube
Mills)
 HAMMER MILL

Principle:
It operates on the principle of impact between rapidly moving
hammers mounted on rotor and the stationary powder material.
 PARTS, CONSTRUCTION &
WORKING

The mill consists of a

• metallic case
• rotor,
• a central shaft with hammers,
• screen,
• feed
• outlet.

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, ADVANTAGES,
DISADVANTAGES
Uses:
It is used to mill dry materials, wet filter press cakes, ointment, slurries etc.

Advantages:
1. It is rapid in action, and is capable of grinding many different types of
materials.
2. As it is a closed system Toxic substances can be ground.
3. They are easy to install and operate, the operation is continuous.

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, CONSTRUCTION &
WORKING

Consists of a loop of metalic pipe with diameter 20-200 mm. The

overall height of the pipe is 2 m. It also consist of----
1. Opening for material feed.
2. Nozzles for inlet of air under pressure.
3. Opening with a classifier which acts as a product outlet.
*** 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, ADVANTAGES,
DISADVANTAGES

Uses:
The mill is used to grind heat sensitive material to fine powder like-
antibiotics, pigments, dyes, cosmetics, vitamins & food products.

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. 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. High energy consumption
4. Not suitable for sticky products.
 DISINTEGRATOR

Principle:
The size reduction is done by impact.
 PARTS, CONSTRUCTION &
WORKING

The mill consists of a metallic body with an inner

undulating surface. Also consist of----
 feed
 screen,
 set of beaters
 rotor
 dust bag
 product outlet
*** The mill consists beaters attached to a rotor. The rotor
moves with help of electricity
 USES, ADVANTAGES,
DISADVANTAGES
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