Milling Pharmaceutical Industry

Milling is mechanical process of reducing the particle size of
solids.
Various terms has been used cursing,
disintegration, dispersion, grinding, and pulverization

1. MILLING
Dr.Ahmad A.Yosef
Industrial Pharmacy 4
th

Lecture 3
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2. Topics
1.Milling definition
2.Pharmaceutical application
3.Size distribution and measurement
4.Types of mills
5.Selection of mills
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3.  Milling is mechanical process of reducing the particle size of
solids.
 Various terms has been used cursing,
disintegration, dispersion, grinding, and pulverization

Benefit of milling
Increase specific surface of the substance.
Increase the free surface energy of milled substance.
Significantly increase the speed of substance and diffusion
processes.
Strengthen the pharmacological activity of substances


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4. Milling
Advantages
1.Mixing is more uniform if
ingredients are roughly
the same size
2.Milling of wet granules can
promote uniform and
efficient drying
3.Increased surface area can
improve dissolution rate
and bioavailability
4.Improved content uniformity
of dosage units
Disadvantages:
1.Excessive heat generation can
lead to degradation, change in
polymorphic form
2.Increase in surface energy can
lead to agglomeration
3.May result in excessive
production of fines or overly
broad particle size
distribution
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5. Pharmaceutical application
Increase surface area by size reduction which affect the
therapeutic efficiency of medical substance , in low soluble
materials.
Examples
Griseofulvin
Penicillin G procaine
Aspirin suppository
Aerosol
suspension
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6. Measurement methods
There are three method involved in size
distribution measurement:
a.Microscopy
b.Sieving
c.Sedimentation
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7. 1.Microscopy
1.Ordinary direct method.
2.Depend of resolving power of the lens.
3.If size close to the wavelength of light can't resolve.
4.Ordinary microscope lower limit is 0.4 micron
5.Ultraviolet lower limit is 0.1 micron
6.Ultra microscope lower limit is 0.01micron

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8. 2.Sieving
A pan with a bottom of wired cloth with square openings , In U.S,
two standard of sieves are used.
The procedure involve shaking, weighing of portion retained, and
taping
Why sieving
1.Most widely used
2.Inexpensive
3.Rapid and Little variation
4.Lower limit is 50 micron
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9. 3.Sedimentation
Used over size range from 1 to 200
microns.
Based on the dependence of the rate of
sedimentation of the particle on their
size expressed by stoke equation.
Pipet method is the simplest means
of incremental particle size analysis.
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10. Types of Mill
A mill consist of three part:
1.Feed chute
2.Grinding mechanism
3.Discharge chute
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11. Milling forces
The principle of operation depends
on:
1.Cutting
2.Attrition
3.Compression Impact
4.Open-circuit and closed-circuit mills
5.Rate of discharge equal rate of feed.
6.Discharge chute designed at the bottom of mills so that
the force of gravity is sufficient to give free discharge
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12. Milling forces
Comminution is characterized by the symbol index –”i”
- the degree of comminution of substances.
“I” equal ratio of the diameter of pieces of material to
the milling (D) to particles diameter after ones (d.)
i = D / d
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13. Types of milling depend on degree of
comminution
The degree of reduction in particle size
1.Large – 2-6 times;
2.Medium - up 6-10 times;
3.Fine - at 10-50 times;
4.Micro fine - in 50-100 times;
5.Super fine - thin (colloidal) – in 100-10000 times.
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14. Classification equipment for milling
according to the technique
1.Cutting machine
2.Attrition machine
3.Compression machine
4.Impact machine
5.Impact - Centrifugal machine
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15. Classification equipment for
milling according to comminution
1.Crushers: for great, medium, fine milling.
2.Mills: for micro fine, superfine (colloid) milling.
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16. Classification equipment for
milling according to breaking
1.Disc
2.Boll
3.Rotor
4.Hammer
5.Rollers and others
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17. Requirements for the
milling process
1.Substances must has initial its composition and
pharmacological properties during the milling process;
2.Periodically to remove enough milled particles from
the sphere of comminution;
3.Prevent formation of dust (sealed enclosures)
4.Appropriate moisture of material
5.The use of sequence connected crushing-milling
machines.
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18. Mills selection:
Initial size of the material and desirable size of final product.
The total amount of material for milling.
Physical and chemical properties of material for milling

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