SIZE SEPARATION

3.1 INTRODUCTION

In pharmaceutical industries, during manufacturing of various formulations the powder (of drug or
excipients) of specific size is required. Size separation plays an important role in such type of processes.
Size separation is a process in which particles of required size are separated from the material of
different size. It is also called as sieving, sifting, separation or classification. It is one of the most
important unit operations. It is usually carried out with size reduction simultaneously. In various
pharmaceutical formulation processes such as tableting, solution, suspension, powder, granules, etc size
separation is performed with different objective. Size separation depends on size, shape, density and
geometry of the particles.

3.2 OBJECTIVES OF SIZE SEPARATION

 In manufacturing of all solid dosage forms such as tablet, capsules, powder, granules [Link]
desired particle size of powder is necessary. During tablet granulation the granules should be
within narrow size range, otherwise, weight variation will take place during tablet punching.
 To separate undesirable particles.
 Any solid material, after milling, never gives particles of the same size but contains particles of
varying sizes. The size-reduced particles then undergo sieving operation to get fractions of
narrow size range.

3.3 APPLICATIONS OF SIZE SEPARATION

 In formulation of uniform dosage form size separation plays an important role.

 To separate undesirable or unwanted particles.
 It helps in formation of solutions rapidly by separating small size particles (increased surface area of
drugs) from large size particles.
 In extraction, solvent can easily penetrate into small particles due to increase in surface area, small
size particles can be separated by size separation.
 Size separation is an important step in solid dosage form manufacturing such as tablet, powder,
granules, capsules etc.
 Particle size is also important in nasal and pulmonary formulations thus size separation is one of the
most important unit operation in such formulations.
 In topical dosage forms such as ointments, pastes and creams size separation is required.
 All the ophthalmic and topical preparations should be free from gritty particles to avoid irritation.
So size separation is very important.
 To increase the stability of some formulations e.g. stability of suspension.
 To optimize the process conditions such as method of agitation, time of screening, feed rate etc.
MECHANISMS OF SIZE SEPARATION
Mechanisms in size separation equipments are listed as follows:
1. Agitation: Sieves are agitated by various ways in up-down motion or in shaking/vibratory mode.
Principle involved in it is:
(a) Vibration: Sieves are vibrated by mechanical or electrical means in order to allow particles to pass
through sieves. Equipment is designed in such a way that a set of sieves can be moved in left right mode
or in up-down motion.
(b) Oscillation: Sieves can be set in ascending order and inclined at certain degree. Particles roll on
sieves and pass through it. For such movement in parallel way to the set of sieves, reciprocating
direction is induced by mechanical or electrical means on shaft.
(c) Gyration: Sieves are placed on rubber sheet and connected to flywheel. It gives rotary movement to
sieves in order to allow particles to spin and pass through sieves.

2. Centrifugal force: In vertical cylindrical sieve particles move at high velocity due to high speed of air
which flows from bottom of equipment through air jet. Motor is fixed within equipment to impart
velocity to particles.

3. Brushing: Powder is passed through sieves by application of brushes in different direction i.e. front -
back or back-forth or in circular motion.

4. Sedimentation: Particles are separated on the basis of their weight through sedimentation process.
Larger particles settle more rapidly while small particles will settle very slowly.

5. Suction and pressure: Powder is passed through bags of defined pore size by suction and lastly
pressure is applied to shake bags to collect the powder at bottom.

6. Elutriation: Particles are separated by fluid flow according to their density. In this case some low
density particles will flow in upward direction due to velocity of fluid while, high density particles will
flow downward. Fluid flows opposite to direction of sedimentation. Fluid velocity play an important role
in this technique.

OFFICIAL STANDARDS OF POWDERS AND SIEVES

The Indian Pharmacopoeia and British Pharmacopoeia specify five grades of powder and the number of
the sieve through which all the particles must pass and not more than 40 per cent shall pass through.
The relevant grades of powder and sieve number are shown in the Table 3.1.

 Sieves used for Pharmaceutical Processes are of the wire mesh type.
 Officially, sieves are identified by their number.
 The number of a sieve indicates the number of meshes (openings) included in a length of 2.54
cm (1 inch) in each direction parallel to the wires.
 It should be noted that officially, it is the number of meshes that is specified and not the number
of wires.
  Thus, a No. 100 sieve has 100 meshes per inch in each direction, but if there were 100 wires
there would be 99 meshes only.
 The mesh size is also dependent on the diameter of the wire or the fabric used.
 Therefore, for officially standard sieves, wire gauge (thickness) is always specified. I.P. doesnot
specify the material of construction of wire.
 Commonly used materials are metals such as iron, coated iron, copper, copper alloys (brass and
phosphor-bronze). stainless steel and non-metals such as hair, silk, nylon, terylene, etc.

3.6.1 Official Standards for Sieves according to I.P. and B.P.

1. Number of Sieve: This is the number of meshes in a length of 2.54 cm (1 in.), in each direction,
parallel to the wires.

2. Nominal Size of Aperture (hole): This is the distance between the wires, so that it represents the
length of the side of the square aperture.

3. Nominal Diameter of the Wire: The wire diameter has been selected to give a suitable aperture size,
but also to have sufficient strength to avoid distortion.

4. Approximate Screening Area Per cent: This standard expresses the area of the meshes as a
percentage of the total area of the sieve.

5. Aperture Tolerance Average Per cent: Some variation in the aperture size is unavoidable and this
variation, expressed as a percentage, is known as the aperture tolerance average.

Table 3.2: I.P. specifications for wire and aperture size Number of Sieves

3.6.2 Perforated Plate Sieves

 Sieves may also be made by drilling holes in metal plate

 . This type of sieves will have circular apertures as against the square apertures of the wire mesh
sieve.
 In general, these sieves are used in the larger sizes and can be made with greater accuracy than
wire-mesh sieves.
 Also, they are less susceptible to distortion in use. This type is commonly used as screens in
impact mills.
 Usually, the holes are spaced with their centers arranged at the apices of equilateral triangles,
so that all the apertures are equidistant.
EQUIPMENT USED IN SIZE SEPARATION

Various equipment used in size separation based on different principles and mechanisms are as listed
below: 1. Sieve shaker 2. Cyclone separator [Link] separator [Link] filter 5. Elutriation tank +

Sieve Shaker

 A polydisperse powder is subjected to size separation to obtain the powder of desired size or
size distribution.
 Sieve shaker is the most commonly used instrument for this purpose in pharmaceutical
industry.

Principle:

 Sieve shaker is based on principle of agitation or vibration.

 Variety of models are available which work on different principle.
 In some cases, agitation or circular vibration or up and down movement of sieves allows
particles to get separated on sieves.

Construction:

 The shaker has a platform for the sieves to rest.

 Sieves are placed on the platform in ascending order of sequence like coarser sieve (sieve no.
10) at the top while fine sieve (sieve no. 80) at the bottom which is connected to a collector pan.
 The other accessories like capping, screws, frame, timer, etc are provided for the smooth
functioning of the shaker.

Working:

 Sample under size separation is placed on topmost region on set of sieves i.e. on coarser sieve
and finally closed with lid.
 The whole set of sieves is placed on shaker and fixed at appropriate position.
 Equipment is turned on and allows the material to get moved on sieves due to vibration or
agitation. Particles will pass through sieves aperture and moves to next sieve untill they get
retained on sieve.
  Particles retained on sieve are called as oversize particles and those passed through sieves are
termed as undersize particles.
 After specified time period (20 minutes), the shaker is turned off. Collect the particles retained
on each sieves

Merits of Sieve Shaker:

 This is a cost effective method of size separation

 The method is most simple and no skilled person is required.
 This is a rapid method of particle size analysis.
 Sieve shaker is able to measure the particles of size upto 50 µm. (Not below 50 µm).

Demerits of Sieve Shaker:

 There are chances of sieves blinding.

 This method is not suitable for size separation of wet material.
 Due to agitation or vibration particles colloids or attacked each other thus chances of size
reduction.
 Not able to measure the particles size below 50 µm.

Applications of Sieve Shaker:

 To achieve size separation of polydisperse powder.

 To carry out particle size analysis.

Cyclone Separator

Principle:

 In cyclone separator the centrifugal force is used to separate particles. The separation depends
on particle size as well as on density of the particles.
 Therefore, cyclone separators may be used to achieve separation on the basis of particle size or
on particle density or both.
 Depending on the fluid velocity, the cyclone can be used to separate all particles or to remove
only coarser particles and allow fine particles to be carried through with the fluid.
Construction:

 It consists of a cylindrical vessel with a conical base.

 The upper part of the vessel is fitted with a tangential inlet and a fluid outlet and at the base it is
fitted with the solid outlet. It uses no moving parts.
 Fluid outlet Upward vortex Downward vortex Solid outlet Tangential inlet suspension

Working:

 The suspension of a solid and gas usually air is introduced tangentially into the separator at a
very high velocity.
 Air gets a rotary movement in the vessel due to the vessel’s shape and its tangential entry.
 A high speed rotating (air) flow is established within a cylindrical or conical container called a
cyclone. The rotatory flow within the cyclone separator causes the particles to be acted on by
centrifugal force.
 The bigger particles are thrown out to the walls, then fall to the conical base and discharged out
through solids outlet.
 The fine particles are carried by the air and passed out through the central outlet at the top.
 A dust bag may be placed at the outlet to collect the fine particles.
 Air passes out of the bag and the fine particles are retained.

Merits of Cyclone Separator:

 It has high efficiency over a broad flow range.

 It requires low capital cost.
 Flow-optimized design is possible.
 It requires relatively small space
 It has high safety during operation under pressure.
 It has ability to operate at high temperatures.
 It has long-term corrosion protection.
 It has low maintenance requirements (no moving parts).
 It can handle liquid mists or dry materials.

Demerits of Cyclone Separator:

 It has high operating costs.

 It has low efficiencies particularly for particle sizes below their cut-off diameter when operated
under low solids-loading conditions.
 It has usually higher pressure loss than other separator types including bag filters and low
pressure drop scrubbers.
 It is subjected to erosive wear and fouling if solids being processed are abrasive or sticky.
Applications of Cyclone Separator:

 Cyclone separator is used to separate the suspensions of a solid in a gas or air. It can be used
with the liquid suspensions of solids.
 General applications in pharmaceutical industries for separation of coarse and fine particles.
 Cyclone separators are used in spray dryer.

3.7.3 Air Separator

air separator is also known as mechanical air classifier or dispersion separator. Air classifiers can only be
used for dry processing. They are normally employed when the particle size that is needed to separate is
too fine to screen.

Principle:

The principle of air separator involves balancing of the centrifugal force, drag force, collision and gravity
to generate a high-precision method of classifying particles according to size and density. The action of
an air current of a certain velocity upon a mass-particle is proportional to the surface presented by this
particle to the air current whereas, the action of the force of gravity upon a mass-particle is proportional
to the volume. Thus, the effect of the force of gravity increases faster than that of an air current of
constant velocity. If these two forces are acting simultaneously, i. e. when particles being in a state of
free fall are exposed to an ascending air current, the force of gravity will dominate over the effect of the
air current as particle dimensions increase. On the other hand, a properly adjusted air current will
oppose the force of gravity and lift up the finest mass-particles. For dry materials of 100-mesh, lighter
and smaller particles are removed by the airflow, while heavier and larger particles are not entrained in
the airflow.

Construction:

 It consists of a cylindrical vessel with a conical base.

 In the upper part of the separator the vessel is fitted with feed inlet, and at the base there are
two outlets, one for line particles and other for heavy particles.

 The rotating disc and rotating blades are attached to the central shaft, to produce air
movement
 Working:

 The sample powder is passed through the feed inlet, which falls on the rotating disc.

 The rotating blades are attached to the same shaft.

 These produce a current of air by the arrows.

 The fine particles are picked up and are carried into space, where air velocity is sufficiently
reduced.

 The fine particles are dropped and ultimately collected at an outlet meant for fine particles.

 The heavy particles (coarse particles) which fall downward are removed at an outlet meant for
heavy particles(coarse particles)

Applications:

 Reducing the fine load on a water flotation system for extracting precious metals from many
types of minerals, including iron, gold, phosphate, etc.
 Upgrading the fineness of milled limestone, silica, fused glass, alumina, lithium carbonate,
copper oxide and others.
 To remove undesirable contaminants from kaolin, hydrated lime, diatomaceous earth and mica.
 Increasing the protein content in wheat flour, chick-pea flour, poultry meal, animal feed and
others. 5. Air separator are used when the separation curve or cutpoint is too fine for screens
(200-400 mesh or finer), when the capacity is too large for screens (up to 800 ton/h) and when
easy adjustability is required to meet various product specifications.
 It is operated in closed circuit combination with pulverizer like ball or tube mills and increases
the efficiency of pulveriser.

Merits:

 It is excellent for de-dusting purpose.

 It produces materials with high uniform fineness.
 It eliminates the blinding and breakage issues associated with screens.
 It has high accuracy.
 It is a dry process.
 With the addition of protective liners, air classifiers can be used to economically process,
abrasive powders, such as silica, flyash and ceramics.
 Air classifier rarely fractures or degrades particles of fragile powders because they do not
operate at pulverizer speeds and most of the feed never makes contact with the rotating parts.
 It can be operated in open or closed circuit.
 This equipment when used in closed-circuit with mills, it maximizes the capacity of the mill and
reduces the mill’s energy consumption.
 It is superior to screens for fine separations.

Demerits: Air classifiers can only be used for dry processing.

3.7.4 Bag Filter

 A bag filter or a bag house or fabric filter is an air pollution control device that removes
particulates (dust) out of air or gas released from pharmaceutical and Manufacturing of
pharmaceutical products such as drugs, vitamins, minerals or herbs involves a broad range of
processes with the potential to generate harmful dust.
 Some of the processes include: drying, mixing, blending, screening, tableting, encapsulating,
coating, milling/sizing, weighing, conveying and packing of dry finished products, etc.
 The pharmaceutical dust can present unique challenges due to the potential health hazards to
the workers, chemical hazards in the industry and air pollution.
 In addition to protect workers, dust recovery and cross-contamination are important safety
considerations.

Principle:

 The use of filter bags for dust collection is based on the principle of filtration, which is a reliable,
efficient and economic methods to remove particulate matter from the gases.
 The dust layer adheres to and is deposited on the surface of the filter bag and the interior of the
filter cloth (the primary dust layer) filters and collects the dust contained in the processed gas.
 The high efficiency of these collectors is due to the dust cake formed on the surfaces of the
bags.
 The fabric primarily provides a surface on which dust particulates collect through the following
four mechanisms:

1. Inertial Collection: Dust particles strike the fibers placed perpendicular to the gas flow direction
instead of changing direction with the gas stream.

2. Interception: Particles that do not cross the fluid streamlines come in contact with fibers because of
the fiber size.

3. Electrostatic Forces: The presence of an electrostatic charge on the particles and the filter can
increase dust capture.

4 Brownian Movement: Submicron particles are diffused, increasing the probability of contact between
the particles and collecting surfaces.
combination of these mechanisms results in formation of the dust cake on the filter, which eventually
increases the resistance to gas flow.
Construction:

 The inside of a bag house is divided into several compartments.

 Each compartment contains several filter bags in which filter cloth sewn into cylindrical shapes is
installed.
 The filter bags are up to 40 cm in diameter and 2 to 10 m long.
 They are suspended with their open ends attached to a manifold.
 The number of bags can vary from a few hundreds to a thousand or more depending upon the
size of the bag house.
 A hopper is provided in the bottom of the compartment to collect the dust removed from the
filter bags. Bag houses are constructed as single or compartmental units.
 In both cases, the bags are housed in a shell made of rigid metal material. The filter bags are
made from: 1. Woven fabric: Interlaced yarn type. 2. Felted fabric: Randomly oriented fibers. 3.
Membranes: PTFE laminated to a woven fabric or felt. 4. Sintered metal fibers: Small metal
fibers randomly oriented on a cylinder. 5. Ceramic cartridges: Fabricated on honeycomb or
cylinder
 It is important to select the filter material of a filter bag to suit the gas temperature, humidity,
gas composition, and dust characteristics.
 The life of a filter bag is several years, but varies greatly depending on the gas and dust
characteristics.
Working:

 The gas entering the inlet pipe strikes a baffle plate, which causes larger particles to fall into a
hopper due to gravity.
 The carrier gas then flows upward into the tubes and outward through the fabric leaving the
particulate matter as a “cake” on the insides of the bags.
 The filter must be cleaned periodically.
 Depending on filter cleaning mechanism, the bag house is classified as:

1. Mechanical shakers:

a. In mechanical shaker bag house, tubular filter bags are fixed onto a cell plate at the bottom of
the bag house and suspended from horizontal beams at the top.
b. Polluted gas enters the bottom of the bag house and passes through the filter, and the dust
collects on the inside surface of the bags.
c. Cleaning of a mechanical shaker bag house is done by shaking the top horizontal bar from which
the bags are suspended.
d. A motor-driven shaft and cam create vibration produced by waves in the bags to shake off the
dust cake.

2. Reverse air:

a. In reverse airbag house, the bags are fixed onto a cell plate at the bottom and suspended from
an adjustable hanger frame at the top.
b. Polluted gas flow normally enters the bag house and passes through the bag from the inside,
and the dust collects on the inside of the bags.
c. These are compartmentalized to allow continuous operation. Before beginning a cleaning cycle,
filtration is stopped in the compartment to be cleaned.
d. Bags are cleaned by injecting clean air into the dust collector in a reverse direction, which
pressurizes the compartment.
e. The pressure makes the bags collapse partially, causing the dust cake to crack and fall into the
hopper below. At the end of the cleaning cycle, reverse airflow is stopped, and the
compartment is ready to work efficiently.

3. Pulse jet:

a. In pulse jetbag house, individual bags are supported by a metal cage (filter cage), which is
fastened onto a cell plate at the top of the bag house.
b. Polluted gas enters from the bottom of the bag house and flows inside the bags. The metal cage
prevents collapse of the bag.
c. Bags are cleaned by a short burst of compressed air injected through a common manifold over a
row of bags.
d. The compressed air is accelerated by a venturi nozzle mounted at the bag house top of the bag.
e. Since the duration of the compressed-air burst is short (0.1s), it acts as a rapidly moving air
bubble, traveling through the entire length of the bag and causing the bag surfaces to flex.
f. This flexing of the bags breaks the dust cake, and the dislodged dust falls into a storage hopper
below.
Applications:

 In pharmaceutical industries: A major concern for pharmaceutical facilities is the safe, efficient
collection of fine dust generated at various manufacturing stages. This is most important for
very fine sub-micron dusts and powders which pose a health threat to employees as well as
cross contamination issues for high purity products.
 Other industries where bag filters find extensive applications are: (a) Metallurgical industry (b)
Foundries (c) Cement industry (d) Chalk and lime plants (e) Ceramic industry (f) Flour mills
 Bag houses may be specifically designed to meet the needs of certain industries or applications.
Some applications and media types include:
(a) Abrasives: Bag house fabrics are designed to withstand and capture abrasive particles.
(b) Acid gases: Bag house fabrics are coated with powdered lime or similar substance to absorb
acid gas.
(c) Coolant and oil mists: Unit is capable of filtering coolant smoke and mist from metal
finishing and forming processes, and machining oil mists.
(d) Explosive media: Unit is capable of filtering explosive dusts, mists, and/or fumes.
(e) Fine powders: Unit is capable of filtering fine powders such as carbon black, talc, pigments,
oxides, and plastic compounding dusts.
(f) Mercury: Bag house fabrics are coated with powdered activated carbon to absorb mercury or
other difficult to capture air pollutants.
(g) Toxic media: Unit is capable of filtering toxic materials such as dust, mist, fume, or smoke
from the air.
h) Welding fumes: Unit is designed specifically for the collection of welding fumes or dust; these
may include flux recovery systems

. Merits

 Key Benefits of bag filters for Pharmaceutical processing are: (a) Worker health protection. (b)
Minimized potential long term liability. (c) Improved product quality. (d) Reduced
housekeeping..
 It has high collection efficiencies for all particle sizes (above 99%), especially for particles smaller
than 10 micron in diameter..
 It has simple construction and operation.
 It has nominal power consumption.
 Dry disposal of collected material.
 It can collect flammable dust also.
 Use of special fibers or filter aids enables sub-micron removal of smoke and fumes.
 It is cost effective when properly designed and maintained.
 Modular design for convenient assembly.
 It can collect other pollutants with certain fabric coating additions.
Demerits:

 It has operating limits due to high carrier gas temperatures, high humidity and other
parameters.
 It has high maintenance and fabric replacement costs.
 Its fabric life may be substantially shortened in the presence of high acid or alkaline
atmospheres, especially at elevated temperatures.
 It is a large size equipment.
 There are problems in handling dusts which may abrade, corrode, or blind the cloth.
 Collection of hygroscopic materials or condensation of moisture can lead to fabric plugging, loss
of cleaning efficiency, large pressure losses.
 Certain dusts may require special fabric treatments to help in reducing leakage or to assist in
cake removal.
 Fabric bags tend to burn or melt readily at higher temperature.
 It requires a lot of maintenance.
 It requires large space.

3.7.5 Elutriation Tank

 Elutriation tank is an installation of multi-stage elutriators in a separation tank.

 Elutriation and Elutriators: Elutriation tank works on the principle of elutriation.
 Elutriation is the process of separation of fine particles from coarse particles. It is the
process in which the particles of the fluid move in a direction opposite to that of the
sedimentation. (Downward movement)”.
 Elutriators are the apparatus used for elutriation process.

Principle:
 Elutriation is a process of particle separation using an upward current of fluid, usually air
or water.
 Insoluble particles in a liquid settle down due to gravity.
 The process is reverse of gravity sedimentation and hence Stoke’s law applies.
 In gravitational elutriation the fluid particles move downward due to sedimentathrn
(force of gravity) while the lighter particles remain upward.
 In centrifugal elutriation, the fluid stream is rotated under high centrifugal force to
suspend the particles.
 These particles which are too large to rotate with direction of flow of fluid, separates
out on the wall of the elutriator.
 However the fine particles move easily with the stream of fluid.
.
Construction:

 An elutriator consists simply of a vertical column (sorting column) with an inlet near the bottom
for the suspension, an outlet at the base for coarse particles, and an overflow near the top for
fluid and fine particles.
 Elutriators containing more than one vertical column of increasing area of cross-section
connected in series are used to achieve better particle size separation.

Working

 All elutriators consist of one or more “sorting columns” in which the fluid is rising at a constant
velocity.
 One column will give a single separation into two fractions.
 If more than one fraction is required, a number of tubes of increasing area of cross-section can
be connected in series (Fig 3.8).
  With the same overall flow-rate, the velocity will decrease in succeeding tubes as the area of
cross-section increases, giving a number of fractions.
 In gravitational sedimentation the particles will move vertically downward while the fluid travels
vertically upward.
 If the velocity of the fluid is less than the settling velocity of the particles, then the particles will
move downward against the stream of fluid and if the velocity of the fluid is more than the
settling velocity of the particles, then the particles will move upward.
 In other words small size particles will move upward while the large size particles will move
downward. Particles in the suspension, introduced into the sorting column will be separated
into two fractions, according to their settling velocities, calculated from Stokes’ law.
 Elutriation is continued until there are no visible signs of further separation taking place or the
rate of change in weights of the products is negligible. In case of a multistage elutriator, the
overflow of preceding column acts as a feed for the next.
 The different relative velocities exist in the sorting columns. The different relative velocities are
obtained due to columns of different diameters.
 The velocity of the stream in the first column is highest and in last column it is lowest.
 Thus, the coarser and denser solids are separated at the first column and the fine product is
obtained at the last.(Particle size and density 1> 2 > 3
 Air elutriation is used to avoid flocculation problem caused by water in the elutriator.
 Air elutriation gives more rapid separation and the separation tends to be sharper than in the
liquids due to the lower resistance of air to particle fall.

Applications:

 Usually, elutriators are used following a size reduction process, with the object of
separating oversize particles, which may be returned for further grinding.
 Elutriation with liquids; the technique is applicable to insoluble solids, such as kaolin or
chalk, which are often subjected to wet grinding followed by elutriation with water.
 Elutriation with gases: the technique is applicable to finer solids that would separate too
slowly in liquids, or where dry processing is required.
 Heavy and light Kaolin can be separated by this process, because the particles of heavy
Kaolin move downward and those of the light Kaolin move upward.

Merits:

 The process is continuous.

 The separation is quicker than with sedimentation
 Elutriation appears more attractive than decantation
 The volume changes need no operator attention.

Demerits:

 The suspension has to be diluted; which may sometimes be undesirable.

 The fluid velocity is not constant across the sorting column, being a minimum at the walls of the
column, and a maximum at the centre.
 The separation size is calculated from the mean volume flow, so that some coarse particles are
misplaced in the overflow, and some fines are misplaced into the coarse overflow.