Size Reduction
Salma M. Mohyeldin, PhD.
Lecturer of Industrial Pharmacy
Faculty of Pharmacy
Alexandria University
AGENDA
Definition & Equipment
objectives Mechanisms
Problems Factors affecting
the process
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Size Reduction
Definition
It is a unit operation of reducing materials to smaller pieces or
converting coarse particles into fine powder by mechanical
means.
Size Reduction (Milling, Grinding,
Comminution, or Pulverization)
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Size Reduction
Objectives
1. Increase the surface area, thus enhancing dissolution and absorption of poorly
soluble drugs.
e.g. Griseofulvin (micronized dose is ½ dose of the original drug).
e.g. Aspirin, Tetracycline (increases solubility and absorption).
2. Pharmaceutical suspensions require a finer particle size (0.5 – 10 µm).
Decreasing particle size reduces sedimentation rate and improves suspension
stability.
3. Increasing the efficiency of solid-solid Mixing =
Variation of particle size affects mixing and
stability of the mixture
As after mixing ------------ Segregation
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Objectives
4. Pharmaceutical inhaled powders
require a finer particle size (1 – 5
µm in diameter) for deeper
deposition in the respiratory tract.
5. Pharmaceutical ointments and creams
require a particle size in the range of
50 -100 µm to ensure the lack of
grittiness of solid particles and prevent
skin irritation.
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Size Reduction
Objectives
6. Galenical preparations: Facilitating the extraction of
the active ingredients from the plant.
7. Increasing the drying rate of wet masses
(Granulation).
8. Reducing the bulk volume of a material to
facilitate transportation.
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Problems of Size Reduction
Decrease the Changes in the
Size reduction Decrease activity
viscosity of color of
of some drugs of some drugs Contamination
some materials materials
• Loss of volatile • Oxidation or
The difference in Toxicity during
oils (e.g., cloves Hydrolysis. E.g., tragacanth
color of yellow, milling, dust may
and cinnamon). • Thermolabile Gum.
orange, and red be toxic to
materials.
mercuric oxides. workers.
• Loss of all or • Change in
part of the water Polymorphic
crystallization. form.
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Size Reduction
Mechanisms of Size Reduction
Cutting Compression Impaction Shear & Attrition
Strain between two Strain between two Strain is at one solid • Attrition: A strain between
or more sharp edges solid surfaces (due to surface. When a two solid surfaces moving in
(Fibrous materials). pressure). moving object strikes opposite directions.
Hard materials. a stationary surface or
vice versa. • Shear is produced when the
particles are compressed
between the edges of two
hard surfaces moving
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tangentially. 8
Size Reduction
Factors Affecting the Size Reduction
1. Hardness or
resistance to scratching
• The hardness of a material affects the ease or
difficulty of grinding.
• Materials have been arranged in order of
increasing hardness in Mohs ´ Scale.
• Ranged between 1 and 10.
< 3 considered soft.
> 7 considered hard.
• It is based on the principle that :
“A material of a lower number can be reduced or
scratched by a material of a higher number”. 9
Factors Affecting the Size Reduction
2. Internal Structure 3. Moisture Content
• Normal granular and crystalline materials can • Materials should be dry or wet, not
be crushed by compression. damp.
• Fibrous materials e,g., plants like glycyrrhiza, • Less than 5% of moisture is suitable
liquorice, and ginger require cutting. if the substance is subject to dry
milling.
• Rubbery or plastic materials are tough and can
be size-reduced at reduced temperature • More than 50% of moisture is suitable
(methyl methacrylates, synthetic gums, waxes, if the substance is subject to wet
and resins). milling.
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Size Reduction
Factors Affecting the Size Reduction
4. Friability 6. Temperature Sensitivity
Friable materials (crystalline material) are
easier to handle than non-friable ones. • Generation of heat during milling leads to
softening or melting of
waxy/thermoplastic materials or drugs
5. Stickiness
containing oils or fats.
• Materials such as gummy & resinous will • Also, it can result in loss of heat-sensitive
adhere to the mill surfaces, reducing components (vitamins & peptides).
efficiency.
• Drying and the addition of an inert • It can be solved by cooling the mill using
substance are beneficial. a water jacket, or passing a cold air
stream, or liquid nitrogen (Cryomilling).
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Factors Affecting the Size Reduction
7. Flammability and
explosiveness
• Combustible materials such as starch, sugars, and sulfur are fire
risks.
• Oxidizers such as perchlorates and nitrates are fire and explosion
risks.
• In grinding these materials:
A. Using an inert gas atmosphere.
B. Using the cooling system (water jacket or using liquid
nitrogen).
C. Avoid high pressure.
D. Use stainless steel, which has less tendency to spark.
E. Device earthing.
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Size Reduction
Equipment
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Size Reduction
I. Cutter Mill
(Rotary Knife Cutter)
Cutting
o It consists of a rotating disc in a cylinder chamber. The disc carries rigid
flying knives that pass with a small clearance over a number of
stationary knives. At the bottom, there is a screen which is changeable
according to the required particle size.
o The feed is introduced from the top, where it is cut several times by
means of stationary and rotatory knives.
o When the product reaches the required size, it discharges
through the screen.
o Used for rubber, wood, fibrous materials, and plastics.
o Cutter mill can be jacketed for cooling to improve size
reduction.
Size Reduction
II. Roller Mill
Compression
o Two rolls made of hard metal rotating against each
other around horizontal shafts.
o The clearance between rolls can be adjusted to control
the degree of size reduction.
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Size Reduction
III. Hammer Mill
Impaction
o Four or more swinging hammers are attached to a disc rotating
at high speed around a central shaft.
o Perforated metal screen covers the discharge opening.
o Feed is introduced into the mill and is subjected togrinding
mainly by direct impact with the hammer and certain attrition
between the hammer and the walls until it is fine enough to
pass through the screen at the lower discharge end.
o Used for fibrous materials (secondary size reduction
equipment) and very hard crude drugs (e.g., Nux vomica
seeds).
o The hammer mill is capable of powdering crystalline
materials that do not soften under milling conditions.
o Cannot be used for thermolabile materials as it generates
heat (water-jacketed). 16
IV. Ball Mill
Impaction & Attrition
o It consists of a hollow steel cylinder lined with porcelain, rotating on
its axis, containing balls of different sizes which occupy 30-50% of
the vessel. Balls are made from the same materials as the lining of
the cylinder.
o During the rotation of the cylinder around a horizontal axis, the
balls fall over the material and reduce it to a fine powder.
Balls are of different sizes:
✓ Large balls start to reduce the particle size of the
coarse particles into smaller particles by impact.
✓ Small balls are then used to reduce the size of the
particles to fine powder by attrition.
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Size Reduction
Rotation speed:
Optimum speed: Balls are At high speed, The balls
At low speed: The
balls slide or roll carried to the top of the mill, will be thrown out to
over each other. then fall across the diameter of the wall by
the cylinder (Cascade motion). centrifugation 18
Advantages:
1. Grinding a wide variety of materials of differing
hardness.
2. It can produce very fine powders.
3. It can be used in a completely enclosed form, which
makes it suitable for use with toxic or hygroscopic
materials.
4. It can be used with an inert atmosphere for grinding
explosive materials.
5. It is suitable for both dry and wet grinding.
Disadvantages:
1. Wear occurs from the balls and from the casing, resulting in contamination of the
product.
2. Soft or sticky materials hold the balls together or cake on the mill sides.
3. The ball mill is a very noisy machine, particularly if the cylinder is made of metal.
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V. Micronizer (Jet-O-Mizer)
(Ultrafine grinders, Fluid Energy Mill)
o The material is suspended at a high air velocity introduced
through a series of nozzles at high pressure.
o Air under high pressure carries the particles and creates a
centrifugal effect in the elliptical chamber. Classification
occurs.
✓ The fine particles go with the air through a cyclone
separator to a product collector.
✓ The large particles go to the outer wall for further
grinding.
o Partial size reduction occurs by impaction (particles strike
against the wall of the chamber) and by interparticle
attrition.
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Size Reduction
V. Micronizer (Jet-O-Mizer)
(Ultrafine grinders, Fluid Energy Mill)
Particles are reduced to 1-20 um.
1. This method is used when fine powders are
required, such as micronization of
griseofulvin (an antifungal drug), vitamins,
and antibiotics.
2. Expansion of gases at the nozzles leads to
cooling, reducing the usual heat generation
that can affect heat-sensitive (thermolabile)
materials.
3. For oxygen or moisture-sensitive materials,
inert gases like nitrogen can be used instead
of normal air.
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Size Reduction
Wet Grinding
o The size reduction process is carried out in wet, not in dry form.
o Instead of processing dry materials, size reduction requires mixing the material
with a liquid medium (water or other solvent) to form a slurry or thin paste
(Levigation) according to the amount of liquid added, which is then loaded into the
grinding equipment.
Advantages:
➢ Elimination of hazards from dust.
➢ Lower energy consumption.
➢ Liquid medium inhibits agglomeration and has
a cooling effect.
➢ It produces more uniform nanoscale particles.
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Size Reduction