1. SIZE REDUCTION Milling prepared by : Anfal Mohammed M.Sc.

2. What is the meaning of size reduction ?
Size refers to physical Dimension of an object. Its expressed in terms of mesh (number of openings per linear inch of a screen)
Reduction refers to the process of decreasing the size.

3. Simple definition of SIZE REDUCTION
Size reduction (milling) is the mechanical process carried out for reducing the size of bigger particles (solid) into smaller ones of desired size and shape with the help of external forces.
COMMINUTION is another term used for size reduction. Various terms (crushing, disintegration, dispersion, grinding, and pulverization) have been used synonymously with comminution depending on the product, the equipment, and the process.

5. ADVANTAGES OF SIZE REDUCTION
Increase the surface area Improving dissolution rate, because in most reactions involving solid particles, the rate of reactions is directly proportional to the area of contact with a second phase
Content uniformity ,Uniform flow, Uniform mixing and drying ,Improve rate of absorption . Smaller the particles greater is absorption
Improve color and/or APIs dispersion in tab. excipient
High surface area means better drying
To improve the handling characteristics
To improve mixing of solid particle together, reducing problem of uniformity of weight and contents of tab.

7. Disadvantages of size reduction
Drug degradation is possible as a result of heat buildup during milling
A possible change of polymorphic form of the API
A decrease in particle size may lead to agglomeration of small particles as a result of static charge that may decrease the dissolution rate and flowability

8. Mechanism of size reduction
Impact —particle is more or less stationary and is hit by an object moving at high speed(hammer)
Compression—particle is crushed by two rigid forces (nutcracker).
Shear or cutting —the material is crushed by means of a sharp blade or blades
Attrition —breaking the edges of the solid either by impact or particle collisions or arising from particles scraping against one another or against a rigid surface (a file).

11. Methods for size distribution measurement
Microscopy: an ordinary microscope is used to measure particles from microns by means of a calibrated filar micrometer eyepiece. With special lenses and ultraviolet light, the lower limit may be extended to 0.1 micron.
Sieving: 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. It most widely used method because of its inexpensive, simple, and rapid with little variation between operators, but its not too much
precise.

12. 3. Sedimentation: this method is based on the dependence of the rate of sedimentation of the particles on their size. Its used over size range of microns. A pipette method (Andreasen) is the simplest means of incremental particle size analysis.( the larger particles settle at faster rate
And fall below the pipette than smaller ones)
4. Electrical stream sensing zone method (Coulter
Counter) (conductivity measurement):
Counting and sizing particles suspended in
Electrolytes by detecting the changes in the
Electrical resistance of the liquid passing the microchannels through two chambers containing electrolyte solutions.

13. Coulter counter

14. SIZE REDUCTION THEORIES
The energy requirement for particle size reduction is a function of input and output of particle size, hardness, strength and other properties of solids
Various theories for energy requirement are:-
Rittinger’s theory: Energy α new surface area formed
Bond’s theory : Energy required for crack propagation α length of the crack
Kick’s theory:- Energy α Ratio of reduction in sizeD1/D2 (input/output)

15. Energy utilization
The most efficient mills utilize less than 1% of the energy input to fracture particles and create new surfaces, the rest energy is dissipated in:
In producing elastic deformation of the particles before fracture occurs (irreversible plastic deformation), which is a waste energy
Transport the material within the milling chamber.
In friction between particles, and between particles and the machine
In noise, heat generation and vibration
Inefficiency of transmission and motor

16. Classification of crushers
It is not generally economical to effect a large reduction ratio in a single machine.
The equipment used is usually divided into classes as given below, according to the size of the feed and the product.
A greater size reduction ratio can be obtained in fine crushers than in coarse crushers

17. TYPES OF MILLING EQUIPMENT

18. Rotary Cutter Mill Principle: Cutting with 2-12 sharp knives.
Use: Cutter mill is used for size reduction of tough & fibrous material like animal tissues, medicinal plants. The size limit of it is 80 mesh . The feed size should be less than I inch and should not exceed the length of the cutting knife. A screen in the bottom controls the size of output.

19. Roller mill
Principal : Material is crushed by the application of stress (attrition). Stress is applied by rotating heavy 2-5 wheels or rollers . The rollers rotates at different speeds so that the material is sheared and compressed as it passes through the gap between the rollers and is transferred from the slower to faster roll, from which it is removed by means of a scraper.
Uses: for crushing seeds before extraction of fixed oil. Also used to crush soft tissue to help in penetration of solvents.

21. Roller crushers

22. Hammer mill
Principal: Material is impact between rapidly moving hammers on a rotor ( up to rpm)& the powder material which fed from top or center. The material discharged through the perforated screen covering the discharge opening which retain coarse material for further grinding
Uses: it is used to mill dry materials, wet filter press cakes, ointments, slurries etc. Brittle material is best fractured by impact from blunt hammers; fibrous material is best reduced in size by cutting edges.

24. Advantages of Hammer mill
1.It is rapid in action, and is capable of grinding many different types of materials. 2. They are easy to install and operate 3. There is little contamination of the product with metal abraded from the mill as no surface move against each other. 4. The particle size of the material to be reduced can be easily controlled by changing the speed of the rotor, hammer type, shape and size of the screen. 5.small space requirements. 6.easy to clean.
Disadvantages
1.Heat buildup during milling is more, therefore, product degradation is possible.2. Hammer mills cannot be employed to mill sticky, fibrous and hard materials.3. The screens may get clogged.4. Wearing of mill and screen is more with abrasive materials.

25. Ball mill or Pebble mill or Tumbling mill
Principal: Material is impact between rapidly moving (steel or pebble)balls & the powder material, both enclosed in hollow cylinder. At low speed, the balls roll over each other & attrition (rubbing action) will be predominant. In ball mill, impact or attrition or both responsible for size reduction.
Uses: Ball mill at low speed is used for milling dyes, pigments & insecticides. Stainless steel balls are preferred in the production of ophthalmic & parental products.

26. Advantages of ball mill:
1.It can produce very fine powder. 2.Ball mill is used for both wet and dry grinding processes.3. Toxic substances can be ground, as the cylinder is closed system. 4.Rod or bars can also be used as grinding media. (example: Sticky material)5. In the ball mill, installation, operation and labour costs are low.
Disadvantages of ball mill:
1.The ball mill is a very noisy machine.2. Ball mill is a slow process.3. Soft, tacky, fibrous material cannot be milled by ball mill.4. difficult to clean and needs high energy

27. FLUID ENERGY MILL (MICRONIZER)
Principle: Fluid energy mill operates on the principle of impact and attrition. In this equipment , the feedstock is suspended within a high velocity air stream . Milling takes place because of high velocity collisions between the suspended particles.
Fluid energy mill It consists of a loop of a pipe, which has a diameter of 20 to 200 mm, depending on the overall height of the loop which may be up to about 2 meters, 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, Solids are introduced into the stream and, as a result of the high degree of turbulence, impact 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 particles size to the order of 100 mesh, enabling the process to yield a product as small as 5 micrometers or less.

28. Uses: It is used for to reduce the particle size of antibiotics & vitamins. Moderately hard materials can be processed for size reduction. Ultra fine grinding can be achieved.
Advantages: 1.Up to 6000 kg of feed is milled per hour. 2. Feed particles of size 12 mm are easily size reduced. 3. Since there is no wear of the mill, contamination is not possible.4. heat-labile material can be milled because of the cooling effect of air and heat exchange bet. Particles and air. 5. air can be replaced with inert gas to decrease the oxidation to susceptible materials.
Disadvantages: 1.Fluid energy mill is not suitable for milling of soft, tacky and fibrous material. 2.The equipment is expensive, because it needs additional accessories particularly fluid energy source and dust collection equipment.

29. Fluidized – ENERGY Mill

30. COLLOID MILL
Principal: Colloidal mill consists of two steel discs having distance (clearance) between them. When the material is passed through these discs, they get sheared. Thus coarse particles are broken down in small particles due to shear.
Uses: Colloidal mill is used for preparing colloidal dispersion, suspension, emulsion & ointments. Fibrous material can be milled using rough surface rotor & stator.

31. SELECTION OF A MILL The choice of the mill is based on:
Product specification (size range, shape, moisture content, physical & chemical prosperities, hard, soft)
Capacity of the mill & production rate requirements
Versatility of operation (wet & dry milling, rapid change of speed and screen, safety)
Dust control (lost of costly drug, health hazards, contamination of plant)
Sanitation (ease of cleaning , sterilization)
Auxiliary equipment (cooling system and dusting collector)
Batch or continuous operation
Economical factors (cost, space occupied and power , labor consumption)

32. Milling process may have the following effects:
May alter the crystalline structure of the API liberating the water causing the clogging of the mill
Hygroscopic material as CaCl2 rapidly absorb moisture to the extent that causing the mass sticks and clogs the mill
The heat during milling softens and melts the API with low melting point as resins, gums, and wax
Excessive heat cause change in the shade of color of pigments