Transcript Milling

Milling
26-2-2014 •
Is the reduction in the size mass by conversion of
the large solid unit mass into smaller one by
mechanical process. This needs energy to break down
the mass into smaller one and this process depends on
the size of the starting material (the feed), the orientation
of the material in the crushing machine, the time of
milling to which these materials are subjected, the type of
mill and the particle size required. The large particles
need large energy than the small one. Different types of
mill give different types of orientation and power.
The process of size reduction is conducted by applying
force which results from different sources (compression,
shearing or tension). Compression is a crushing force, shearing is a
cutting force and tension is the force that tend to elongate a particle
or pull it apart. Each particle will have initial defect of different
degrees and possible internal stress as a result of prior
manufacturing operations. Cracks started inside the mass and when
the force applied exceeds the force of attraction between particles,
the cracks will be bigger and a reduction in the particle size proceeds
as the force is continued.
• Various terms (crushing, disintegration, dispersion,
grinding, and pulverization) have been used
synonymously with comminution depending on the
product, the equipment, and the process .
• Milling equipment is usually classified as coarse,
intermediate or fine according to the size of the
milled product. Coarse milling produces particles
larger than 20-mesh, intermediate milling produces
particles from 200 to 20 mesh (74 to 840 microns),
and fine milling produces particles smaller than 200mesh.
Advantages of Milling:
• Increase surface area which increases the solubility, and
dissolution rate of material so enhance its bioavailability.
•
Increase in the area of contact between the solid and the
dissolving fluid.
•
Improve color and/or active ingredient dispersion in tablet
excipient.
• Improve mixing of materials together so give fewer problems in
uniformity of weight and contents of tablets.
• Higher surface area means better drying.
• Improve mixing of materials together so give fewer problems in
uniformity of weight
Disadvantages of Milling:
• A possible change in polymorphic form of the active ingredient
rendering it less or totally inactive or unstable. i.e. will affect the
therapeutic activity of drug.
•
Possible degradation of the drug as a result of heat buildup during
milling by oxidation or adsorption of unwanted moisture due to the
increased surface area.
• A decrease in bulk density may cause problems in the flowability of
material.
• A decrease in particle size may create static charge problems causing the
small drug particles to agglomerate therefore effectively decreasing
surface area. This may decrease the dissolution rate.
Pharmaceutical Application
• The surface area per unit weight, which is known as the
specific surface, is increased by size reduction. This
increased specific surface affects the therapeutic
efficiency of medicinal compounds that possess a low
solubility in body fluids by increasing the area of contact
between the solid and the dissolving fluid. Thus, a given
weight of a finely powdered medicinal compound
dissolves in a shorter time than does the same weight of a
coarser powder.
• The control of fineness of griseofulvin led to an
oral dosage regimen half that of the originally
marketed product.
• The rectal absorption of aspirin from a theobroma
oil suppository is related to particle size.
• Increased antiseptic action has been
demonstrated for calomel ointment
when the particle size of calomel has
been reduced.
• The size of particles used in
inhalation aerosols determines the
position and retention of
the particles in the bronchopulmonary
system
• Size may affect texture, taste, and rheology of oral
suspensions in addition to absorption.
• Extraction from animal glands (liver & pancreas),
and from crude vegetable drugs, is facilitated by
comminution. The time required for extraction is
shortened by the increased area of contact
between the solvent and the solid and the
reduced distance the solvent has to penetrate into
the material. Similarly, the time required for
dissolution of solid chemicals in the preparation
of solutions is shortened by the use of smaller
particles.
• 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.
• In the manufacturer of compressed tablets, the
granulation of the wet mass results in more
rapid and uniform drying. The dried tablet
granulation is then milled to a particle size and
distribution that will flow freely and produce
tablets of uniform weight. The flowability of
powders and granules in high-speed filling
equipment and in tablet presses affects product
uniformity.
• The mixing or blending of several solid
ingredients of a pharmaceutical is easier and
more uniform if the ingredients are
approximately the same size. This provides a
greater uniformity of dose.
• Solid pharmaceuticals that are artificially colored are
often milled to distribute the coloring agent to ensure
that the mixture is not mottled and is
uniform from batch to batch.
• Lubricants used in compressed tablets and capsules
function by virtue of their ability to coat the surface of
the granulation or powder. A fine particle size is
essential if the lubricant is to function properly. The
milling of ointments, creams, and pastes provides a
smooth texture and better appearance in addition to
improved physical stability.
Size Distribution and Measurement
•
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 particles. For convenience of mathematical
treatment, an irregular particle is considered in terms
of an equivalent sphere. The size of the particle can
then be expressed by a single parameter that is the
diameter (d). It is only required that the surface area is
proportional to the square of the diameter and the
volume is proportional to the cube of the diameter.
•
The volume of a particle may be determined by
displacement in a liquid and equated to the volume of
a hypothetic sphere possessing an equivalent diameter.
As the volume of a sphere is πd3/6, the equivalent
diameter of an irregular particle with a volume V is:
• The effective diameter of particles based on
their rate of sedimentation is commonly used
in pharmacy. The rate of sedimentation is the
time required for the particle to settle
between two fixed points in a suitable liquid.
The effective or Stokes' diameter is the
diameter of a sphere that requires the same
time to settle between two fixed points in the
liquid as does the irregular particle. The
arithmetic average diameter is the sum of the
diameters of the separate particles divided by
the number of particles and it is equal to:
Using the logarithmic form of this equation, the geometric
mean diameter of a number of particles is calculated by using
the following equation:
Size distributions that follow the probability law are
referred to as normal or Gaussian distribution as
shown in the figure
below:
Methods for Size Distribution
Measurement:
1- Microscopy:
It is the most direct method
for size distribution measurement.
In an ordinary microscope is used
to measure particles from 0.4-150
microns. With special lenses and
ultraviolet light, the lower limit may
be extended to 0.1 micron.