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CHAPTER

MILLING

DEFINITION: Milling can be defined as The mechanical process of reducing the particle size
of solids.
Other terms used for milling are: Crushing, disintegration, dispersion, grinding and
pulverization.
Pharmaceutical Applications of Milling:
Surface area per unit weight known as specific surface, increased by size reduction. This
affects the therapeutic efficiency of low solubility medicinal compounds.

Increased antiseptic action for calomel ointments is due to reduced particle size

Size may affect texture, taste and rheology of oral suspensions in addition to absorption.

Extraction from animal glands (liver and pancreas) and from crude vegetable drugs is
facilitated by comminution.
The drying of wet masses may be facilitated by milling, which increases the surface area
and reduces the distance the moisture must travel within the particle to reach the outer
surface.
The mixing of several solid ingredients of a pharmaceutical is easier and more uniform if
the ingredients are approximately the same size.

A fine particle size is essential for proper function of Lubricants used in compressed
tablets and capsules function by their ability to coat the surface of granulation or powder.
MILLING EQUIPMENTS

Milling equipment is usually Classified as:


1. Coarse Milling: produces particles larger than 20-mesh
2. Intermediate Milling: produces particles larger than 200 to 20-mesh (74-840
microns)
3. Fine Milling: produces particles smaller than 200-mesh
SIZE DISTRIBUTION AND MEASUREMENTS
In naturally occurring particulate solids and milled solids, the shape of particles is
irregular and the size of the particles varies within the range of the largest and smallest
particle.
There is no known method of defining an irregular particle in geometric terms; however,
statistical methods have been developed to express the size of an irregular particle in
terms of a single dimension referred to as its diameter.

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For convenience of mathematical treatment, an irregular particle is considered in terms of


an equivalent spheres. The size of the particles can then be expressed by a single
parameter, d (diameter). The volume of particles may be determined by displacement in a
liquid . As the volume of a sphere is d3 /6. The equivalent diameter of an irregular
particle with a volume V is: d = 3 6 V/
METHODS OF SIZE DISTRIBUTION
1. MICROSCOPY
2. SIEVING
3. Electrical stream sensing zone method
a. (Coulter counter)
4. SEDIMENTATION
5. Other methods
1. Microscopy
The most direct method of size distribution measurement. For White light, an ordinary light is
used to measure particles from 0.4 to 150 microns. With special lenses and ultraviolet light, the
lower limit may be extended to 0.1 micron. The size range of ultra microscope is from 0.01 to
0.2 micron. The diameters of the particles on the slide are measured by means of a calibrated
filar micrometer eyepiece.

2. Sieving
It is the most widely used method for measurement of particle size distribution b/c it is
inexpensive, simple and rapid with little variation b/w operators. The limit is 50 to 10
microns. The procedure involves the mechanical shaking of a sample through a series of
successively smaller sieves and the weighing of the portion of the sample retained on
each sieve. Sieving or screening is a method of separating a mixture or particles into 2 or
more size fractions, the over sized materials are trapped above the screen, while
undersized materials can pass through the screen. Sieves and screen are usually used for
larger particle sized materials i.e., greater than approximately 50m (0.050mm).

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MILLING

Size Equivalents
Two scales that are used to classify particle sizes are the US Sieve Series and Tyler
Equivalent, sometimes called Tyler Mesh Size or Tyler Standard Sieve Series.

3. Electrical stream sensing zone method (Coulter counter)


Sample preparation and analysis conditions
Powder samples are dispersed in an electrolyte to form a very dilute suspension, which is usually
subjected to ultrasonic agitation for a period to break up any particle agglomerates. A dispersant
may also be added to aid particle de-agglomeration.
Principle of measurement
The particle suspension is drawn through an aperture accurately drilled through a sapphire
crystal set into the wall of a hollow glass tube. Electrodes situated on either side of the aperture
and surrounded by an electrolyte solution, monitor the change in electrical signal that occurs
when a particle. The range of particle is 0.1 to 1000 microns, momentarily occupies the orifice

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MILLING

and displaces its own volume of electrolyte. The volume of suspension drawn through the orifice
is determined by the suction potential created by a mercury thread rebalancing in a convoluted
U-tube. The volume of electrolyte fluid which is displaced in the orifice by the presence of a
particle causes a change in electrical resistance between the electrodes that is proportional to the
volume of the particle. The change in resistance is converted into a voltage pulse which is
amplified and processed electronically. Pulses falling within precalibrated limits or thresholds
are used to split the particle size distribution into many different size ranges. In order to carry out
size analysis over a wide diameter range it will be necessary to change the orifice diameter used,
to prevent coarser particles blocking a small-diameter orifice. Conversely, finer particles in a
large-diameter orifice will cause too small a relative change in volume to be accurately
quantified.

4. Sedimentation Method
This method is used over a size range from 1 to 200 microns. This method is based on the
dependence of the rate of sedimentation of the particles on their size as expressed by
Stokes equation: d stokes =

Where
d stokes = Stokes diameter,
= viscosity of dispersion fluid, x/t = rate of sedimentation or distance of fall x in time t,
g = gravitational constant, and 0 are the densities of the particle and the medium
Stokes equation is applicable to free spheres that are falling at a constant rate. If the
concentration does not exceed 2 %, there is no significant interaction b/w the particles, and they
settle independent of one another.

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The pipette method (Andreasen) is the simplest method of incremental particle size analysis. A
1% suspension of powder in a suitable liquid medium is placed in the pipette. At given interval
of time, samples are withdrawn from a specified depth without disturbing the suspension and
they are dried so that the residue may be weighed. By means of Stokes equation, the particle
diameter corresponding to each interval of time is calculated, with x being the height of the
liquid above the lower end of the pipette at time t when each sample is withdrawn. As the sizes
of the particles are not uniform, the particles settle at different rates.

5. Other Methods
The other methods include adsorption, electrical conductivity, light and x-ray scattering.

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