partical size reduction

Question 1

what is particle size reduction and what are the different mechanisms

Answer 1

The mechanical process of reducing larger size unit
masses into smaller unit masses.

milling, comminution, crushing, disintegration, dispersion, pulverization, choppin

Question 2

what are the objectives of size reduction

Answer 2

1. Enhancement of dissolution and bioavailability of hydrophobic drugs by increasing the specific surface area (“surface area / unit wt“).
2. Improvement of content uniformity (homogeneous mixing) by virtue of increasing the number of particles per unit weight.
3. Improvement of flow properties of powder with needle shape or extremely irregular by changing to spherical shape (→good flow can lead to better mixing)
4. Some excipients need to be in very fine powder to do well their function (such as lubricants or colours).
5. Facilitate drying.
6. Reduce grittiness of topical preparation and reduce the irritation of the eyes for ophthalmic suspensions
   .
7. Extraction from plants materials is facilitated by size reduction.

Question 3

what are the disadvantages of size reduction

Answer 3

1. Polymorphic transformation may happen during the grinding
   process.
2. Development of amorphous structures.
3. Possible drug degradation as a result of heat buildup.
4. Possible contamination from the size reduction equipment.
5. Development of surface electric charge
    Excessive increase of surface area would create surface charge which enhances agglomeration and thus decreasing the effective surface area. This would subsequently retard powder flow and dissolution.

Question 4

what is the theory of size reduction

Answer 4

1. The initial portion of the stress-strain diagram is defined by the
   Hooke’s law:
    stress-strain relation is linear
    the deformation is reversible (elastic deformation)
   → the particle returns to its original shape if the stress is
   removed Slope of the linear line (Young’s modulus) and expresses stiffness or softness.
2. After the yield point:
    stress-strain relation becomes nonlinear
    The deformation becomes irreversible (plastic deformation)
   → Particle remains deformed after the release of the applied
   stress

Question 5

what is crack progression

Answer 5

Size reduction starts with opening of any small crack that
were initially present.

the bugger the particle the better

Question 6

where does the energy used in size reduction go

Answer 6

2% for breaking (fractures)

the rest:
Deformation of particles
 Transport of material within the
milling chamber
 Friction between particles
 Friction between particles and
mill
 Heat
 Sounds and vibration

Question 7

how can we describe hardness

Answer 7

on mohs scale
 Values from 1-3 indicate soft materials
 Values from 8-10 indicate hard materials

Question 8

what is toughness

Answer 8

 Tough material are those than can undergo deformation (i.e. plastic
and rubber).
 Tough material may be more difficult to mill than hard and brittle
material. For example:
 chalk and rubber: chalk is harder than rubber, but more easily to
be reduced in size because it is less tough.
 Green leaves with high moisture vs dry leaves.
 Toughness can be often reduced by reducing temperature of
milling.

Question 9

In summary……
Hard and tough = difficult to mill (e.g. some metals)
Hard and not tough (brittle) = easy to comminute (e.g. glass,
ceramic, chalk).
Soft and tough (e.g. plastic materials) = difficult to
comminute (e.g. many polymers)-(advisable to reduce
temperature)
Soft and not tough = easiest to comminute (e.g. talc)

Question 10

how does milling influence size distribution

Answer 10

1. An initial normal size distribution is transformed into a size-
   reduced bimodal size distribution. This is due to differences
   in the fracture behaviour of coarse and fine particles
2. If milling is continued a unimodal size distribution reappears.
   However this is not normal, but a positively skewed size
   distribution.

Question 11

what are the mechanisms of size reduction

Answer 11

1. Cutting
   It involves application of a force over a narrow area of
   material (particle) using a sharp edge (e.g. blade)
2. Compression
   The particle is crushed by application of pressure between
   two surfaces
3. Impact
   The particle is hit by an object moving at high speed.
4. Attrition
   The particle is rubbed between two surfaces that are
   moving relative to each other.

Question 12

how does the cutter mill work (cuttings)

Answer 12

 Product is loaded through a feed hopper
 Series of knives attached to horizontal
rotor (rotating knives), which act against
a series of stationary knives attached to
the mill casing.
 Lower part consists of screen (classifier),
which control the particle size: it retains
the material in the mill, until a sufficient
degree of size reduction has been
reached

used for: granules and fibrous materials

range= 5cm-100micro

Question 13

how does the roller mill work (compression)

Answer 13

range = 10cm- 900 micro

 Two cylindrical rolls mounted horizontally capable of rotating
on their longitudinal axes. The two rolls are separated by small
gap.
 One roll is driven directly and the other runs free by friction
 The gap between the rolls can be adjusted to control the
extent of size reduction

used for seeds to extract oils

Question 14

how does the hammer mill work (impaction)

Answer 14

range 5cm-10micro

can be used for everthing,raipd,easy,the degree can be controlled

disadvantages
 Potential clogging of the screens
 Heat build-up during milling (unsuitable for heat-sensitive
drugs)
 Not suitable for sticky, soft or fibrous material

the size reduction depends on
 Rotor speed
 Material feed rate
 Material density
 Screen size

 The material is fed into a strong metal
case.
 Inside the case hammers are attached
to a motor driven shaft.
 The material is milled by impact of the
hammer and thrown for another
impact with the wall of the metal case.
 Particles are retained within the mill by
a screen, until they are small enough to
pass through the screen.
 These screens do not act as
sieves (we can not expect
the largest particles leaving
the mill to be 0.5 mm in size
if the mill is fitted with a 0.5
mm mesh screen).
 This is due to the particle’s
angle, when it exits through
the screen.

Question 15

how does the vibration mill work (impaction)

Answer 15

range
1cm-1micro

 Vibration mills are filled to
approximately 80% total volume
with porcelain or steel balls.
 During milling the whole body of
the mill is vibrated and size
reduction occurs by repeated
impaction.
 Milled particles fall through a
screen at the base of the mill.

Question 16

how does the ball mill work (impaction and attrition)

Answer 16

range= 100micro-1micro
can be used for abrasive materials

disadvantages
Not suitable for soft or fibrous materials
Difficulty in cleaning
Long milling times
High power consumption

 It consists of a hollow cylinder mounted such that it can be
rotated on its horizontal longitudinal axis.
 The cylinder contains balls that occupy 30-50% of the total
volume The balls inside the cylinders constitute the
grinding media
 They can be made of different size (0.6 to 7
mm), shape and material.
 Generally in the same mill, balls with many
different diameters are contained:
 Large balls tend to breakdown coarse
material
 Small balls helps to form the fine product

two factors affect it:
speed and amount of material

 At low speed, the mass of balls will only slide over
each other (minimal size reduction by attrition)
 At high speed (Impact speed), the balls are
thrown out to the mill wall, where they remain
due to centrifugal forces (no size reduction
occur)
 At intermediate speed (At 60-85% of the critical
impact speed), a cascading action is produce:
the balls are carried out to the top then fall in
cascade across the chamber of the mill (most
efficient size reduction by impact and attrition)

Critical Impact Speed : The speed at which the ball begins
to centrifuge with the mill
=
76.6/√ D

 Excessive feeding produces a cushioning effect, as the thick
bed of material tends to absorb the impact energy of the
balls
 Too little feed causes loss of efficiency and abrasive wear of
the mill parts

Question 17

how does the fluid energy mill work (attrition and impaction)

Answer 17

range= 5cm-1micro

used for
 Suitable for producing very fine powders.
 Thus it is mainly used to enhance drug dissolution and
bioavailability.
 Suitable for thermolabile drugs: expansion of introduced air has
cooling effect.
 Suitable for oxidizable drugs: in this cases inert gas such as N2
can be used instead of air.
 Unsuitable for soft, tacky and fibrous materials.

affected by
1. Grinding air pressure: The higher the air pressure, the higher the particle
acceleration, the higher the milling efficiency.
2. Classifier size
3. Feed rate: It affects the so called particle mean free path (distance that a
particle travels before colliding with another particle). The larger the
distance the higher the acceleration of particles and the higher the energy
of collision and the more the milling efficiency.
Higher feed rate diminishes the mean free length, as the milling chamber is
crowded with particles leading to reduction of milling efficiency.

 It is also called jet mill or micronizer.
 It consists of a hollow toroid (doughnut-shape).
 Both circular designs and oval-path designs
are available.
 This mill has no moving parts.
 The high kinetic energy of the air causes:
 Impact of particles with other particles and with the walls
of the mill
 Some attrition between particles

A. Particles are fed from the side.
B. A fluid, usually air, is injected as a high-
pressure jet through nozzles at the bottom of
the loop.
C. The high velocity of the air gives rise to zones
of turbulence carrying particles. Here
particle-particle and particle-mill collisions
generate size reduction.
D. A particle size classifier (sieve) ensures that
particle are retained into the mill until
sufficiently fine.

Question 18

how does the pin mill work (impaction and attrition)

Answer 18

range=10mm-10micro

 Two discs, with closely spaced pins, rotate against one another at
high speeds.
 As the particles travel outwards under the influence of centrifugal
force, milling occurs by impaction with the pins and by attrition
between pins.

Question 19

how does the roller mill (wet) work (attrition)

Answer 19

 Use:
 for size reduction of suspensions and semi-solids
(pastes, or ointments).
 Size reduction:
 300 µm – 1 µm

 So far we mainly spoke about dry milling (milling where the
material is dispersed in air medium).
 However some type of milling are carried out dispersing the
solid material in water (or other liquid) → wet milling
 This offers two main advantages:
1. It eliminates dust (possible hazard for the operator)
2. It allows to lower the particle size even further than using
dry milling

 Mills most commonly used for wet granulation:
 Ball mill (described before)
 Roller mill
 Colloid mill

 Two or three porcelain or metal rollers are mounted horizontally with
an adjustable gap which can be as small as 20 µm
 The rollers rotates at different speeds so that the material is sheared
as it passes through the gap.

Question 20

how does the colloid mill work (attrition) (wet)

Answer 20

 It operates by shearing relatively thin layer of material
between two surfaces:
 One moving at high speed (rotor)
 The other is stationary (stator)

Question 21

what are the factors influencing milling

Answer 21

1. Nature of material
   Hard material are abrasive to the mill.
   Ball, vibration and roller mills are the most resistant to abrasion.
   Fibrous material cannot be crushed by pressure or impact, but
   must be cut.
2. Moisture content
    The presence of more than 5% moisture does not allow good
   comminution. High moisture level often produce a sticky mass
   upon milling.
3. Stickiness
    Adherence of material to grinding surfaces or screen becomes
   clogged.
    This usually happens with gummy or resinous material. especially
   with heat build-up.
4. Temperature
    Heat during milling softens and melts materials with a low melting
   point (e.g. gums and resins)
    Heat-sensitive materials can be degraded
    For this reasons, often the milling chamber must be kept cooled

Question 22

based on what do we select the method

Answer 22

1. Material properties
   Hardness
   Stickiness
   Abrasiveness
   Structure (fibrous material must be cut)
2. Properties of the final product
   Degree of size reduction required
   Shape (method bases on attrition tend to give more spherical
   particles)
3. Sanitation (Ease of cleaning and sterilization)
4. Capacity of the mill and production rate requirements
5. Economical costs:
   Cost
   Power consumption