1. Size Reduction

2. Objectives of Size Reduction
Size Reduction means the reduction of materials to smaller sizes.
Objectives of Size Reduction
To produce smaller particles (in the preparation of suspensions or to facilitate the mixing of powders).
To increase surface area (to increase adsorptive properties).
In drugs that are crushed to expose cells prior to extraction.
Reduce the bulk of a material, since shipping charges may be based on volume.

3. Factors Affecting Size Reduction
The pharmaceutical industry uses a great variety of materials, including chemical substances, animal tissues, and vegetable drugs which may be hard (seeds), fibrous (barks or roots) or spongy (peels).
Thus, the methods of size reduction are numerous, and selection of the suitable method involves the material properties that may influence the process.

4. The properties that affect size reduction include:
HARDNESS
TOUGHNESS
ABRASIVENESS
STICKINESS
SOFTENING TEMPERATURE
MATERIAL STRUCTURE
MOISTURE CONTENT
PHYSIOLOGICAL EFFECT
PURITY REQUIRED
BULK DENSITY
RATIO OF FEED SIZE TO PRODUCT SIZE

5. HARDNESS
As hardness is a surface property of the material and it is differs than strength, thus, it is possible for a material to be very hard, but if it is brittle, the size reduction is easy.
Moh's Scale is a scale of hardness in which range the hardness of a series of mineral substances has hardness numbers between 1 and 10, ranging from graphite to diamond.
In general, the harder the material the more difficult to be reduced in size.

7. TOUGHNESS
Toughness is more important than hardness, so that a soft but tough material may present more problems in size reduction than a hard but brittle substance;
For example, compare the ease with which a stick of blackboard chalk can be broken and the difficulty to break a rubber.
Toughness of many pharmaceutical materials, as in fibrous drugs is often related to moisture content.
(the toughness of a `green' twig and the brittleness of a dry one).

8. ABRASIVENESS
Abrasiveness is a property of hard materials, particularly those of mineral origin, and limit the type of machinery that can be used.
During the grinding of some very abrasive substances the final powder has become contaminated with more than
0.1 % of metal from the grinding mill.

9. STICKINESS
It is a property that cause difficulty in size reduction, because material may adhere to the grinding surfaces, or the meshes of screens and become choked.
Pharmaceutical substances that are gummy or resinous may be troublesome, particularly if the methods used for size reduction generate heat.
Solve this problem by complete dryness and the addition of inert substances (as addition of kaolin to sulphur)

10. SOFTENING TEMPERATURE
Many of the size reduction processes result in the generation of heat, which may soften some substances example: Waxy substances, such as stearic acid, and drugs containing oils or fats
It may be possible to cool the mill, either by a water jacket or by passing a stream of air through the equipment or to use liquid nitrogen.

11. MATERIAL STRUCTURE
Some substances are homogeneous in character, but the majority show some special structure
Mineral substances may have lines of weakness along which the material splits to form flake-like particles
Vegetable drugs have a cellular structure often leading to long fibrous particles.

12. MOISTURE CONTENT
Moisture content influence a number of the properties that affect size reduction as hardness, toughness or stickiness.
In general, materials should be dry or wet but not damp. Usually, less than 5 % of moisture is suitable if the substance is to be ground dry, or more than 50 % if it is subjected to wet grinding.

13. PHYSIOLOGICAL EFFECT
Some substances are very potent (as hormone drugs) and small amounts of dust may have an effect on the operators.
To solve this problem:
Use enclosed mills to avoid dust.
Special air extraction systems are desirable.
Wet grinding can eliminates the problem entirely.

14. PURITY REQUIRED BULK DENSITY
Certain types of size reduction apparatus cause the grinding surfaces to wear, thus such methods must be avoided if a high degree of purity of product is needed.
BULK DENSITY
When all other factors being equal, the output of the machine is related to the bulk density of the substance.

15. RATIO OF FEED SIZE TO PRODUCT SIZE
Machines that produce a fine product require a small feed size. Thus, it may be necessary to carry out the size reduction process in several stages with different equipment;
for example, preliminary crushing, followed by coarse grinding and then fine grinding.

16. Mechanisms of Size Reduction
There are four main methods of effecting size reduction, with different mechanisms:
Cutting.
the material is cut by means of a sharp blade or blades.
Compression.
the material is crushed by application of pressure.

17. Impact.
Occurs when the material is stationary and is hit by an object moving at high speed or when the moving particle strikes a stationary surface. In either case, the material shatters to smaller pieces.
Attrition.
The material is subjected to pressure as in compression, but the surfaces are moving relative to each other, resulting in shear forces which break the particles.

18. Attrition (pressure and
Mechanisms of size reduction
Common example
Diagram
Method
Approximate
increase in
Fineness
of product
Scissors Shears
Cutting
Nutcrackers
Compression
Hammer
Impact
File
Attrition (pressure and
friction)

19. METHODS OF SIZE REDUCTION
The term mill is used normally for machines for size reduction.
Cutting and compression have limited uses in pharmaceutical practice.
Impact and attrition are used much more widely, both separately and in combination, and there is a great variety in each type.

20. Cutting
On the small scale, size reduction by cutting can be affected by a knife or a cutter.
On a large scale, a cutter mill is used.

21. CUTTER MILL CUTTER MILL The principle of operation:
knives are attached to a rotor and act against stationary knives in the casing.
The lower part consists of a screen, so that material is retained in the mill until a sufficient degree of size reduction has been effected.
Application:
The method is used to obtain a coarse size reduction of soft materials.
Examples:
Roots, peels or woods, prior to extraction.
CUTTER MILL

22. Compression
On the small scale size reduction by Compression carried out by a pestle and mortar.
On a large scale, roller mill is used.

23. ROLLER MILL ROLLER MILL The principle of operation: Application:
The roller mill has two cylindrical rolls of stone or metal, mounted horizontally, which rotate on their longitudinal axes. Usually, one of the rolls is driven directly while the second runs free, so that when
ROLLER MILL
material is placed above the rolls it is drawn in through the nip and the second roll is rotated by friction.
The gap between the rolls can be adjusted to control the degree of size reduction.
Application:
The roller mill is used for crushing seeds prior to extraction of fixed oils, or bruising soft tissues after cutting to aid solvent penetration in extraction.

24. Impact
On the small scale size reduction by Impact carried out by the shattering of brittle substances with a hammer or with a pestle and mortar.

25. HAMMER MILL HAMMER MILL The principle of operation:
the hammer mill consists of a central shaft to which four or more hammers are attached.
These are mounted with swivel joints, so that the hammers swing out to a radial position when the shaft is rotated.
The lower part of the casing consists of a screen through which material can escape.
The screen can be changed according to the particle size required.
HAMMER MILL

26. Advantages
It is rapid in action, and is capable of grinding many
different types of materials.
(b) The product can be controlled by variation of rotor speed, hammer type, and size and shape of mesh.
(c) Operation is continuous.
(d) No surfaces move against each other, so that there is little contamination of the product with metal abraded from the mill.

27. Disadvantages
The high speed of operation causes generation of heat that may affect thermolabile materials or drugs containing gum, fat or resin.
The mill may be water-cooled, if necessary, to reduce this heat damage.
(b) The rate of feed must be controlled carefully, otherwise
the mill may be choked, resulting in decreased efficiency or even damage.
(c) Because of the high speed of operation, the hammer mill is susceptible to damage by foreign objects such as stones or metal in the feed.
Magnets may be used to remove iron, but the feed must be checked visually for any other contamination.

28. Application:
Applications include the powdering of barks, leaves, roots, and crystals.
With cutting edges to the hammers, the method is useful for granulation of damp masses to produce greater uniformity than is obtained by sieve granulation.
The hammer mill can’t used for sticky materials that choke the screen.

29. Attrition
Size reduction by attrition can be effected in the laboratory by using pestle and mortar.
In small scale mechanical method is required using the roller mill .

30. The principle of operation:
ROLLER MILL
The principle of operation:
Two or three rolls in metal or porcelain are mounted horizontally with a very small adjustable gap in between.
ROLLER MILL
The rolls rotate at different speeds, so that the material is sheared as it passes through the gap and is transferred from the slower to the faster roll, from which it is removed by means of a scraper.
Application:
Used for size reduction and dispersion
of solids in suspensions, semisolids as
pastes; or ointments.

31. Combined Impact and Attrition
The mechanisms of impact and attrition can be combined in two forms of mill.
In the ball mill the particles receive impacts from balls or stones and are subjected to attrition as the balls slide over each other.
In fluid energy mills the impacts and attrition occur between rapidly moving particles.

32. The principle of operation:
BALL MILL
The principle of operation:
The ball mill consists of a hollow cylinder mounted in such a way that it can be rotated on its horizontal axis with a rotational frequency depend upon the diameter of the mill ≈ 0.5 r.p.s
BALL MILL
The cylinder may be of metal, porcelain or of rubber, to reduce abrasion. The balls may be of metal, porcelain or stones (pebble mill).
The cylinder contains balls that occupy 30 to 50 per cent of the mill volume.

33. The ball size being dependent on the size of the feed and the diameter of the mill. Usually a mill 1 m in diameter will use balls of 75 mm, In practice, the balls are damaged, so that a range of sizes from 20 mm upwards are used. This gives a better product, since the larger balls crush the feed and the smaller ones form the fine product.
BALL MILL
The cylinder may be of metal, porcelain or of rubber, to reduce abrasion. The balls may be of metal, porcelain or stones (pebble mill).

34. Importance factors in the operation of the ball mill:
The amount of the material in the mill is of importance:
too much exerting a reduced effect
too little leading to loss of efficiency and to abrasion.
The speed of rotation:
At low speeds, the mass of balls will slide or roll over each other and negligible
size reduction will occur.
Low speed with sliding

35. High speed with centrifuging
At high speeds, the balls will be thrown out to the wall by centrifugal force and no
grinding will occur.
High speed with centrifuging

36. Correct speed with cascading
At about two-thirds of the speed at which centrifuging just occurs, movement takes place as shown in Fig. (c), that is, the balls are carried almost to the top of the mill
and then fall in a cascade (tumble) across the diameter of the mill.
Correct speed with cascading
By this means, the maximum size reduction is effected by impact of the particles between the balls and by attrition between the balls.

37. Low speed with sliding
High speed with centrifuging
Correct speed with cascading

38. Advantages It is capable of grinding a wide variety of materials of
differing character and of different degrees of hardness.
It can be used in a completely enclosed form; which
makes it especially suitable for use with toxic materials.
It can produce very fine powders.
It can be used for continuous operation, and a classifier can be used in conjunction with the mill, so that particles of suitable size are removed while oversize particles are returned.
It is equally suitable for wet or dry grinding processes.

39. Disadvantages
Wear occurs, principally from the balls, but partially from the shell and this may result in the contamination of the product; with abrasive materials this may exceed 0.1%
Soft or sticky materials may cause problems by caking on the sides of the mill or by holding the balls in aggregates.
The ball mill is a very noisy machine, particularly if the casing is of metal, but much less if rubber is used.

40. Application: Ball mills are applicable to a wide variety of materials,
large ones being used for grinding ores prior to manufacture of pharmaceutical chemicals
small versions for the final grinding of drugs or for grinding suspensions.

41. FLUID ENERGY MILL The principle of operation: Fluid Energy Mill
The fluid energy mill is consist of a loop of pipe. A fluid, usually air, is injected at high pressure through nozzles at the bottom of the loop, giving rise to a high velocity circulation in a very turbulent condition.
Fluid Energy Mill

42. Solids are introduced into the stream and, as a result of the high degree of turbulence, impacts and attritional forces occur between the particles.
A classifier is incorporated in the system, so that particles are retained until sufficiently fine.
The feed to the mill needs to be pre-treated to reduce the particle size to 100 mesh, enabling the process to yield a product as small as 5 μm or less.
Fluid Energy Mill

43. Advantages
The particle size of the product is smaller than that produced by any other method of size reduction.
Expansion of gases at the nozzles leads to cooling, counteracting the usual frictional heat which can affect heat-sensitive materials.
Since the size reduction is by inter-particulate attrition there is little or no abrasion of the mill and so virtually no contamination of the product.

44. For special cases with very sensitive materials it is possible to use inert gases.
Having a classifier as an integral part of the system permits close control of particle size and of particle size distribution.
The method is used where especially fine powders are required, as antibiotics, sulphonamides and vitamins.

45. Selection of Size Reduction Method
Different mills will give differing products from the same starting material:
Particle shape may vary according to whether size reduction is by impact or attrition
The proportion of fines may vary, so altering colour, appearance, and properties.

46. Methods used for various size ranges
Examples
Typical
methods
Degree of size
reduction
Rhubarb
Cutter or compression
mills
Large pieces
Liquorice,
cascara
Impact mills
Coarse
powders
Rhubarb,
belladonna
Combined impact and
attrition mills
Fine powders
Vitamins,
antibiotics
Fluid energy mills
Very fine

47. Selection of Degree of Size Reduction
The use to which a powder is to be put, controls the degree of size reduction.
The important factor is that the cost of size reduction increases as the particle size decreases. Thus, it is economically undesirable to powder a substance to a finer degree than is required.

48. Powder
If a substance is to be used directly in the form of a powder as indigestion powders or dusting powder, a fine powder is needed.
Suspension
When a drug is suspended in a liquid it should be in the form of a very fine powder, as Light Kaolin, and this is especially important if the suspension is to be injected, as in the case of procaine penicillin.

49. For extraction
Soft drugs such as Gentian need only be sliced or crushed
Harder drugs such as Liquorice or Belladonna should be in coarse to moderately coarse powders.
Special characters may exert an effect:
The constituents of Ipecacuanha are of low- solubility so that a fine powder is used to improve the penetration of the solvent into the particles.
Cascara is usually extracted with water and swells when moistened, making a coarse
powder preferable as finer grades would
form an impenetrable mass.

50. The effect of degree of size reduction on the properties:
The viscosity of mucilage of tragacanth decreases with finer powders
The viscosity of mucilage of acacia increases with finer powders, where low grade gums may be improved by grinding.
Adsorption is a surface property, so that the adsorptive power of a substance is improved by grinding.
If a drug contains volatile oils, the greater surface area and the additional heat generated in grinding to a finer powder increase the loss of oil.