Particle Size Reduction - Pharma Notes
Size Reduction
Size reduction is a process of reducing large solid unit masses into small unit masses, coarse particle or fine particles.
Size reduction process is also referred to as commination and grinding.
When the particle size of solid reduced by mechanical means it is known as milling.
Size reduction operation divided into two category –
1. Grinding & Cutting – If material is solid
2. Emulsification & Atomization – if material is liquid
Objectives
• Dissolution and therapeutic efficacy
• Extraction
• Flow ability
• Mixing
• Formulation
Mechanism of size reduction
· Impact – this involve hammer or bar at high speed (hammer mill). Particle Size 50-8,000 µm.
· Compression- particle crushed b/w rollers by the application of force (roller mill). Particle Size 50-10,000 µm.
· Cutting – the material cut by a sharp blade (cutter mill), Particle Size 100-80,000 µm.
· Attrition - arising from particles scraping against one another or rubbing action (colloidal mill, roller mill). Particle Size 1-50 µm
· Impact and Attrition – ball mill, fluid energy mill, Particle Size 1-2,000 µm.
Advantage of size reduction
· Content uniformity
· Uniform flow
· Effective extraction of drug
· Effective drying
· Improve physical stability
· Improve dissolution rate
· Improve rate of absorption
· Increase surface area and viscosity
· Facilitates bioavailability, uniform mixing and drying
Disadvantage of size reduction
· Drug degradation
· Poor mixing
· Contamination
Factors affecting size reduction
– Hardness, toughness, abrasiveness, stickiness, material structure, bulk density, physiological effect Particle shape, Polymorphism, Temperature, and Feeding rate.
Hardness – It is easier to break soft material than hard materials. Ex: For iodine hammer mill is used.
Fibrous – These are tough in nature. A soft, tough material has more difficulty than a hard, brittle substance. Ex: Raowulfia, Ginger. Here cutters can be used.
Elastic / Sticky –Become soft during milling. Ex: synthetic gums, waxes, resins. Low melting substances should be chilled before milling. These are milled using hammer, colloid or fluid energy mill.
Melting point –Waxy substances, fats and oils are softened during size reduction due to heat generated. This is avoided by cooling the mill and the substance.
Hygroscopic –Certain substances absorb moisture content rapidly. This wet mass hampers the milling process. Ex: Potassium carbonate. Closed system such as porcelain ball mill is used.
Moisture content – presence of more than 5% moisture influences hardness, toughness, stickiness of substance, in general material having moisture content below 5% are suitable for dry grinding and above 50% for wet grinding.
Purity required – the size reduction of such hard substance leads to the abrasive wear of milling parts, causing contamination.
Laws governing size reduction
• Griffith Equation - The amount of force to be applied depends on the crack length.
• Kicks Law - Work required to reduce the size of a given quantity of material is constant for the same reduction ratio regardless of the original size.
• Rittinger ’s Law - Worked use for particulate size reduction is directly proportional to the new surface produced.
• Bond’s Law - Worked used to reduce particle size is proportional to the square root of the diameter of the particle produced.
Classification of mills
• Hammer mill
• Ball mill
• Fluid energy mill or ultra-fine grinder or micronizer
• EDGE Runner Mill
• END Runner Mill
• Quadro co mill
• Multi Mill
• Roller Mill
• Rotary Mill
• Disintegrator
Hammer mill
Principle –
· It operates on the principle of impact between rapidly moving hammers mounted on rotor and the stationary powder material.
Parts –
· Consists of a metal casing, enclosing a central shaft, to which 4 or more swinging hammers are attached.
· Lower part of casing consists of a screen, through which material can pass and collected in a suitable receiver.
Construction & Working –
· A hammer mill is essentially a steel drum containing a vertical or horizontal rotating shaft or drum on which hammers are mounted.
· The hammers swings on the ends or fixed to the central rotor.
· The rotor is rotates at a high speed inside the drum while material is fed into a feed hopper.
· The material is put into the hopper which is connected with the drum.
· The material is powdered to the desired size due to fast rotation of hammers and is collected under the screen
· Impact mill using high speed rotor up to 10000 rpm with a peripheral speed up to 7600 meter per minute
· Dry materials, wet filter press cake, wet granules, ointments and slurries
· Size reduction up to 20 to 40µ
· Circular hole design for fibers and herringbone design for crystalline materials and continuous operation jump- gap screen for abrasive and clogging materials.
· Micro pulverizer for nonabrasive materials
Determination of particle size
· Rotor speed
· Feed rate
· Clearance between hammers and grinding plates
· Size of discharge opening
Advantages –
· It is rapid in action, and is capable of grinding many different types of materials.
· They are easy to install and operate, the operation is continuous.
· There is little contamination of the product with metal abraded from the mill as surface move against each other.
· 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.
Disadvantages –
· Heat buildup during milling is more, therefore, product degradation is possible.
· Hammer mills cannot be employed to mill sticky, fibrous and hard materials.
· The screens may get clogged.
Uses
• Brittle material is best fractured by impact from blunt hammers.
• Fibrous material is best reduced by cutting edges.
Variants
• Fitzatrick comminuting machine – fitz mill
• Strokes tornado mill
Ball mill
Principle –
• It operates on the principle of impact and attrition between the rapidly moving balls and the powder material, both enclosed in a hollow cylinder.
• Both wet and dry grinding, up to 10µ
• Pebble, rod mill, tube mill and Hardinge mill
• Sliding, cascading and centrifuging
• The critical speed is n=76.6/D2=KD (feed particle)
• Optimum diameter of the ball= D ball
Parts
• Consists of a hollow cylinder mounted on a metallic frame such that it can be rotated along its longitudinal axis.
• Cylinder contains balls occupying 30–50 % of mill volume.
• Weight of ball is constant; Size depends on the feed quantity and diameter of mill.
Determination of particle size and Shape
· Size of ball
· Feed rate
· Speed of rotation of cylinder
Advantages:
· It can produce very fine powder.
· Ball mill is used for both wet and dry grinding processes.
· Toxic substances can be ground, as the cylinder is closed system.
· Installation, operation and labour costs are low.
Disadvantages:
The ball mill is a very noisy machine.
Ball mill is a slow process.
Soft, fibrous material cannot be milled by ball mill.
Uses
Produced fine powder, can grind large variety of materials.
As it is a close system toxic substance can be ground.
Fluid energy mill or ultra-fine grinder or micronizer
Principle
It operates on the principle of impact and attrition.
• Air or steam at pressure of 100- 150 psi
• Particle size to 1-20µ
• Feed should be pre milled to 20 to 100 mesh
• Nozzle design and direction of air jets
• Efficiency of air compressors
• Efficiency of filters and separators
Parts
Consists of a loop of pipe with diameter 20-200 mm. The overall height of the pipe is 2 m.
Inlet for feed and a series of nozzles for air, inert gas. Outlet with classifier which prevents the particles to pass until they become sufficiently fine.
Construction
It consists of a loop of pipe, which has a diameter of 20 to 200 mm , depending on the overall height of the loop ,which may be upto about 2 m .
There is an inlet for the feed and a series of nozzles for the inlet of air or an inert gas.
It also has an outlet with a classifier which allow the air to escape but prevents the particles to pass until they become sufficiently fine.
Working
The air or inert gas is introduced with a very high pressure through the nozzles .Solids are introduced into air steam through inlet .due to high degree of turbulence, impact and attritional forces occurs between the particles. The fine particles are collected through a classifier .Fluid energy mill reduces the particles to 1 to 20 micron. To get a very fine powder, even up to five micron, the material is pretreated to reduce the particle size to the order of 100 mesh and then passed through fluid energy mill.
Determination of particle size and Shape
· To speed of air/inert gas
· The impact between the feed and air.
Uses
• The mill is used to grind heat sensitive material to fine powder.
• The mill is used to grind those drugs in which high degree of purity is required.
Advantages
• The mill is used to grind the material to fine powder.
• The particle size of powder can be controlled due to the use of a classifier.
• There is no wear of the mill and hence there is no contamination of the product.
• It is useful for grinding heat sensitive substances such as sulphonamides, vitamins and antibiotics.
Disadvantages
• Tendency of forming aggregates or agglomerates after milling.
• Generation of amorphous content due to high energy impact.
• Formation of ultra-fine particles
• High energy consumption.
EDGE Runner Mill
Principle
• The size reduction is done by crushing due to heavy weight of stone.
Construction
• It consist of two heavy rollers and may weigh several tons.
• The roller move on a bed which is made up of granite or stone.
• Each roller has a central shaft and revolve on its axis.
• The rollers are mounted on horizontal shaft and move around the bed
Working:
• The material to be ground is placed on the bed with the help of the scrapper in such a way that it comes in the path of the stone wheel.
• These stones revolve on its own axis and at the same time travel around the shallow stone bed.
• The material is ground for definite period.
• The powder is collected and passed through a sieve to get powder of required size.
Advantages
• Does not require attention during operation.
Disadvantages
• More space than other mill, Contamination, Time consuming, not use for sticky materials.
Uses
• Grinding tough material to fine powder.
END Runner Mill
Principle
• Size reduction is done by crushing due to heavy weight of steel pestle.
• Shearing stress is also involved during movement of mortar and pestle.
Construction
• It is considered as mechanical mortar pestle.
• It consist of a steel mortar which is fixed to a plate.
• The construction of mortar is connected to horizontal shaft bearing a pulley so the plate with mortar can be rotated at high speed.
• The pestle is dumb-bell shaped and bottom of pestle is flat.
• Construction of pestle is done in such a way that it can be raised from mortar for cleaning and emptying.
Working
• The material to be ground is placed in the mortar.
• The mortar revolves at a high speed.
• The revolving mortar causes the pestle to revolve during this process, size reduction is achieved.
Advantages
• End runner mill provides moderately fine powder and operates successfully with fibrous materials, bark, woods fruits, leaves, etc.
• Wet grinding with very viscous material such as ointments and paste is also possible.
Disadvantages
• Not suitable for unbroken or slightly broken condition of drug.
Uses
• Use for fine grinding.
Quadro co mill
• Control feed product into upper conical screen chamber
• A rotating impeller calibrates incoming material
• Calibrated product then passes through to the lower chamber
• A second intensifying impeller accelerates the particles.
• Particles are continuously delivered to “action zone” between screen and impeller
• Particles are size reduced (as fine as 150 micron) and instantly discharged through screen openings
Multi mill
• Multi mill machines are widely used for wet and dry granulation, pulverization etc.
• SS beaters having knife and impact edges rotate within a selected screen
• The material fed in the hopper enters into the processing chamber where it moves to the pentery and passes through screen
• Output & quality of final products depend on (I) shapes of beaters (Knife/ impact edge) (ii) speed (iii) size of screen
Roller mill
Principle
• Material is compressed by application of stress and attrition.
• Stress is applied by rotating heavy wheels, Muller or rollers.
Parts
• 2 cylindrical rollers of stone or metal mounted horizontally, having diameter ranging from few mm to a meter.
• They rotate in longitudinal axis, one roller is run by motor and other freely.
Determination of Particle size
• Gap between rollers controlled to obtain desired particle size.
Uses
• For crushing of seeds before extraction of fixed oils.
Variants
• Multiple/ Corrugated rollers
• Ribbed/ Saw toothed rollers
Rotary cutter mill
Principle
• Size reduction involves successive cutting/shearing the feed material with help of sharp knife.
Parts
· Hopper
· Milling chamber – horizontally mounted rotor disk consisting 2-12 rotating knives spaced uniformly and casing has stationary knives.
· Screen
· Discharge chute
Determination of particle size and shape
• Rotor size
• Gap between the 2 sets of knives
• Sieve
Uses
• Size reduction of tough fibrous materials
• Medicinal plants, animal tissue are converted to small parts
Variants
• Double runner disc mill
• Single runner disc mill
Disintegrator
Principle
• The size reduction is done by impact
Parts
• Consist of a steel drum enclosing a central shaft, which has a disc to which 4 beaters are fixed.
• The side are upper inner surface of drum is rough.
• Lower part of casing consists of a detachable screen.
Use
• To powder all type of drugs including very hard drugs.
Other important technique in size reduction
Sono-crystallization –
• Utilizes ultra sound of frequency range 20-100 kHz for inducing crystallization.
• It is an effective means of size reduction and controls size distribution of API.
Spray Drying –
• It is a common method of drying a liquid feed through a hot gas.
• This hot gas is air, but sensitive material such as ethanol required oxygen free drying and nitrogen gas.
Supercritical fluid process –
• It is a dance non-condensable fluid whose temperature and pressure are grater then its critical temperature and critical pressure.
• Drug particle are solubilized within super critical fluids and re-crystallized to get greatly reduced particle size.
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