PARTICLE SIZE REDUCTION

PARTICLE SIZE

The size of particulate solids and liquid droplets is a key factor for achieving optimal formulation and manufacture of pharmaceutical products

Particle size of the drug and other powders in the formulation

ultimately impacts the physical performance of the drug product and the subsequent pharmacological effects of the drug

PARTICLE SIZE REDUCTION

It is the process of reduction of large solid units into small units.

Size reduction process is also referred to as

comminution and grinding

When the particle size of solids is reduced by mechanical means it is known as

milling

If the material is solid, the process is called

grinding and cutting

If it is liquid,

emulsification or atomization

OBJECTIVE OF SIZE REDUCTION

• To aid efficient processing of solid particles by facilitating powder mixing or the production of suspensions

• Some special functions of size reduction, such as exposing cells prior to extraction or reducing the bulk volume of a material to improve transportation efficiency

  • Dissolves faster

  • Mixing becomes easier

  • Extract active ingredient

OBJECTIVE OF SIZE REDUCTION

• To aid

efficient processing of solid particles by facilitating powder mixing or the production of suspensions

Some special functions of size reduction,

such as exposing cells prior to extraction or reducing the bulk volume of a material to improve transportation efficiency

Some special functions of size reduction, such as exposing cells prior to extraction or reducing the bulk volume of a material to improve transportation efficiency

• Dissolves faster

• Mixing becomes easier

• Extract active ingredient

INFLUENCE OF MATERIAL PROPERTIES ON SIZE REDUCTION

• Crack propagation and toughness

• Surface hardness

• Energy requirements of size reduction process

• moisture content

CRACK PROPAGATION AND TOUGHNESS

• Size reduction or comminution

• Propagated through regions of a material that possess the most flaws or discontinuities, and is related to the strain energy in specific regions

• Stress in material is concentrated at the tip of a crack

• Ease of comminution depends on the brittleness or plasticity of the material and their relationship with crack initiation and propagation

CRACK PROPAGATION AND TOUGHNESS

• Propagated through regions of a material that possess the

most flaws or discontinuities, and is related to the strain energy in specific regions

CRACK PROPAGATION AND TOUGHNESS

• Stress in material is concentrated at the

• tip of a crack

CRACK PROPAGATION AND TOUGHNESS

• Ease of comminution depends on the

brittleness or plasticity of the material and their relationship with crack initiation and propagation

Hardness of a material can be described by

its position in a scale devised by a German mineralogist called Mohs

More quantitative measurement of surface hardness was devised by

Brinell 

Harder materials

are more difficult to comminute and can lead to abrasive wear of metal mill parts, which then cause product contamination

Materials with large elastic components, such as rubber,

are extremely soft yet difficult to size reduce

• Materials such as rubber which are soft under ambient conditions

• waxy substances such as stearic acid which soften when heated

• “sticky” materials such as gums

• are capable of absorbing large amounts of energy through elastic and plastic deformation without crack initiation and propagation.

This type of polymeric material, which resists comminution at ambient or elevated temperatures, can be more easily reduced by

lowering the temperature below the glass transition point of the material. When this is carried out the material undergoes a transition from plastic to brittle behavior and crack propagation is facilitated

Moisture content below 5% is suitable for

dry grinding

moisture content greater than 50%

if wet grinding is to be carried out

ENERGY REQUIREMENTS OF SIZE REDUCTION PROCESS

• Only a very small amount of the energy put into a comminution operation actually affects size reduction.

• Estimated to be as little as 2% of the total energy consumption, the remainder being lost in many ways, including elastic deformation of particles, plastic deformation of particles without fracture, deformation of metal machine pasts, interparticle friction, particle machine wall friction, heat, sound and vibration

INFLUENCE OF SIZE REDUCTION ON SIZE DISTRIBUTION

• Uneven milling

• Particles aggregation

SIZE REDUCTION METHODS

• Cutting Methods

• Compression Methods

• Impact Methods

• Attrition Methods

• Combined Impact and Attrition Methods

CUTTING METHODS

Principle of operation

– it consists of a series of knives attached to a horizontal rotor which act against a series of stationary knives attached to the mill casing.

CUTTING METHODS

Size reduction range

– 100 to 100,00 um

During milling, size reduction occurs by

fracture of particles between the 2 sets of knives, which have a clearance of a few mm.

Screen is fitted in the base of the mill casing and

acts to retain material in the mill until sufficient degree of size reduction has been effected.

CUTTING METHODS

• Useful in producing a

• coarse degree of size reduction of dried granulations prior to tableting and fibrous crude drugs such as roots, peels, or barks prior to extraction

CUTTER MILL

• shear rates present in cutter mills are useful in producing a coarse degree of size reduction of dried granulations prior to tableting.

COMPRESSION  METHODS

• Size reduction by compression can be carried out on a small scale using a mortar and pestle

RUNNER MILLS

• End runner and edge runner mills are

• mechanized forms of mortar and pestle type compression comminution (Large scale)

END RUNNER MILL

Size reduction range:

50-10,000 um

END RUNNER MILL

• weighted pestle is turned by the friction of material passing beneath it as the mortar rotates under power

EDGE RUNNER MILL

• has the pestle equivalent mounted horizontally and rotating against a bed of powder, so that size reduction occurs by attrition as well as compression (such techniques are now rarely used in pharmaceutical production)

ROLLER MILLS
Size reduction range:

1000 to more than 100,000 um

ROLLER MILLS

• uses 2 cylindrical rolls mounted horizontally and rotated about their long axis.

• one of the rollers is driven directly while the second is rotated by friction as material is drawn through the gap (decides how small the particles would be, usually for suspensions and ointments) between the rollers

IMPACT  METHODS

• hammer 

• vibration 

HAMMER MILLS

size reduction range 

50-8000 um

HAMMER MILLS

consist of a series of four or more hammers, hinged on a central shaft which enclosed within a rigid metal case

VIBRATION MILLS

size reduction range 

1-1000 um

VIBRATION MILLS

It filled to approximately 80% total volume with porcelain or steel balls. During milling the whole body of the milling is vibrated and size reduction occurs by repeated impaction.

ATTRITION  METHODS

Size reduction range

– 1 to 200 um

ATTRITION  METHODS

• Produce size reduction of

• solids in suspensions, pastes or ointments

2 OR 3 PORCELAIN OR METAL ROLLS

• 2 or 3 porcelain or metal rolls are mounted horizontally with an adjustable gap, which can be as small as 20 um. The rollers 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.

BALL MILLS

size reduction 

1-200 um

BALL MILLS

• consist of a hollow cylinder mounted such that it can be rotated on its horizontal longitudinal axis. 

BALL MILLS

• The cylinder/Mills usually contain

• balls with many different diameters owing to self attrition, and this helps to improve the product as the large balls tend to break down the coarse feed materials, and the smaller balls help to form the fine product by reducing void spaces between balls

FLUID ENERGY MILLING

size reduction 

1-50,000 um

FLUID ENERGY MILLING

Acts by

particle impaction and attrition

FLUID ENERGY MILLING

It is also known as a

jet mill or micronizer

FLUID ENERGY MILLING

• A fluid, usually air, is injected as high pressure jet through nozzles at the bottom of the loop. 

• The high velocity of the air gives rise to zones of turbulence into which solid particles are fed. The high kinetic energy of the air causes the particles to impact with other particles with sufficient momentum for fracture to occur.

The high velocity of the air

gives rise to zones of turbulence into which solid particles are fed.

The high kinetic energy of the air

causes the particles to impact with other particles with sufficient momentum for fracture to occur.

Fluid energy:

Collide with each other or a chamber. Commonly used because it is easier.

PIN MILLS

size reduction 

10-10,000 um

PIN MILLS

• 2 discs with closely spaced pins rotate against one another at high speeds. It is influenced by centrifugal force.

AGITATION METHODS

• achieved by electrically induced oscillation, mechanically induced vibration of the sieve meshes or gyration in which sieves are fitted to a flexible mounting which is connected to an out-of-balance flywheel

• output efficiency of gyratory sieves is usually greater than that of oscillation or vibration methods.

BRUSHING METHODS

• A brush is used to reorient particles on the surface of a sieve and prevent apertures becoming blocked

• NOTE: the brush should not force the particles through the sieve by distorting either the particles or the sieve mesh

CENTRIFUGAL METHODS

• particles are thrown outwards onto a vertical cylindrical sieve under the action of a high-speed rotor inside the cylinder

• current of air created by the rotor movement also assists the sieving process, especially where very fine powders are being processed

• wet sieving can also be used to effect size separation and is generally more efficient than dry sieving methods.

BY SEDIMENTATION

• Utilizes the differences in settling velocities of particles with different diameters

• Particles less than a given diameter can be recovered from a fixed distance below the surface of the liquid

• A single separation can be performed simply by removing the upper layer of suspension fluid after the desired time.

One of the simplest forms of sedimentation classification

uses a chamber containing a suspension of solid particles in a liquid, which is usually water.

Disadvantages of these simple methods are that they are batch processes and discrete particle fractions

cannot be collected.

BY ELUTRIATION

• Fluid flows in an opposite direction to the sedimentation movement

• Particles can be divided into different size fractions depending on the velocity of the fluid

• The largest particles are found in the center, the smallest towards the outside along the tube walls

BY CYCLONE SEPARATION

• Particles in air or liquid suspension are often introduced tangentially into the cylindrical upper section of the cyclone, where the relatively high fluid velocity produces a vortex that throws solid particles out onto the walls of the cyclone.

• Coarser particles separate from the fluid stream and fall out of the cyclone through the dust outlet, whereas finer particles remain entrained in the fluid stream and leave the cyclone through the vortex finder

• A series of cyclones having different flow rates or different dimensions could be used to separate a powder into different particle size ranges.

• The most common type of cyclone used to separate particles from fluid streams is the

• reverse-flow cyclone