PHR 306: Pharmaceutical Engineering

FILTRATION
 Filtration
• Filtration may be defined as the separation of an insoluble solid
from a fluid by means of a porous medium that retains the solid
but allows the fluid to pass. The term ‘fluid’ includes both liquids
and gases.
 Filtration

• In another way, Filtration is the separation of undissolved,

particulate, suspended solids from a fluid mixture by passage
of most of the fluid through a septum or membrane that
retains the solids on or within itself.
• Expression or Sedimentation is not filtration.
• Thickening of the membrane by undissolved solids helps in
filtration.
 Cont…
• Feed or Slurry : The suspension of solids and liquids to
be filtered is known as feed or slurry.
• Filter medium: The porous medium through which the
slurry is forced to pass is called filter medium.
• Filter cake: The solids collected on the filter medium.
• Filtrate: Clear liquid that passes through the filter.
• Cake filtration: When solids collected on the filter
medium is the desired product then the process is
known as the cake filtration.
 Pharmaceutical Importance of Filtration
Solid/liquid filtration -
• Improves the appearance of solution or a syrup.
• Improves safety of parenteral products like injections or infusions.
• Removes potential irritant, e.g. Eye drop.
• Filtration is frequently the method of choice for sterilization ( to do that
particles as small as 0.2 µ must be removed) of solution that are
chemically or physically unstable under heating condition.
• Sterile filtration of bulk drug solution prior to an aseptic crystallization
process eliminates the possibility of organisms being occluded within
crystals.
• Waste solids must be separated from the waste liquids prior to its disposal
(Waste Water Treatment)
 Pharmaceutical Importance of Filtration
• Certain operations, such as the extraction of vegetable drugs, may yield a
turbid product with a small quantity of fine suspended colloidal matter, this can
be removed by filtration.
Solid/gas filtration -
• Solid gas filtration is used in the removal of suspended solid material from air
in order to supply air of the required standard (by HEPA filter) to the places of
production of antibiotics, biological products and vaccines.
• Solid gas filtration can remove microbes from air of areas where sterile
products are being manufactured.
Fluid-fluid filtration -
• Decreases degree of turbidity from two immiscible liquids.
• Removes suspended oils from aqueous solutions. Such as: aromatic waters,
syrups, elixirs, eye drops etc.
Clarification -
• gives a polishing effect to a liquid.
Classification of Filters
A) By Driving Force :
(i) Gravity (Gravity Filters);

(ii) Superatmospheric pressure applied upstream of the septum

(Pressure Filters);

(iii) Subatmospheric pressure applied downstream of the septum

(Vacuum Filters);

(iv) Centrifugal force across the septum (Centrifuges).

Classification of Filters ……..

B) By Filtration Mechanism :
(i) Filtered solids are stopped at the surface of the medium and pile
upon one another to form a cake of increasing thickness (Cake
Filtration).

(ii) When the solids are trapped within the pores or body of the medium
(Filter-medium Filtration / Surface Filtration / Screen Filtration).

(iii) Trace amounts of solids undergoing a filter-medium filtration

(Clarification).

C) By Functions :
The process goal may be
i. dry solids (the cake is the product of value),
ii.clarified liquid (the filtrate is the product of value), or
iii.both.
Classification of Filters ……..

D) By operating cycle:
(i) Discontinuous / Intermittent / Batch: Filtrate is continuously
removed but the separation of filtered solids requires stopping the operation.
(ii) Continuous: Discharge and filtrate are separated steadily in an
uninterrupted fashion.

E) By nature of solids : Cake filtration may involve an accumulation of solids

that is compessible or incompressible.
Process/Principle of filtration

• Pores of filter medium are smaller than

the size of the particles to be
separated.
• Filter medium is placed on a support
• Slurry is passed over the filter medium
• Fluid flows through the filter medium
due to pressure differential across the
filter.
• Gravity works on liquid column.
• Solids are retained on the membrane.
• After the preliminary layer of particles
is deposited, then the filter medium
serves only as a support.

Process of filtration
 Mechanism of filtration
The mechanism of filtration is based on two operations. These are-
a) The flow of solid is resisted by the filter medium while the liquid
is allowed to pass.
b) As the filtration proceeds the retention of solids on the filter
media goes on increasing which acts as a secondary and
sometimes more efficient filtering medium.

Slurry
Filter cake

Filter medium

Filtration

Filtrate
 Mechanism of filtration
• Straining
• Similar to sieving, i.e., particles of
larger size can’t pass through smaller
pore size of filter medium.

• Impingment
• Solids having the momentum move
along the path of streaming flow and
strike (impinge) the filter medium.
Thus the solids are retained on the
filter medium.
 Mechanism of filtration
• Entanglement
• Particles become entwined
(entangled) in the masses of
fibres (of cloths with fine hairy
surface or porous felt) due to
smaller size of particles than the
pore size. Thus solids are
retained within filter medium.

• Attractive forces
• Solids are retained on the filter
medium as a result of attractive
force between particles and
filter medium, as in case of
electrostatic filtration.
 Theories of filtration
The flow of a liquid through a filter follows the basic rules that
govern the flow of any liquid through the medium offering
resistance.
The rate of flow may be expressed as:
Rate = driving force/resistance
Filtration is not a steady state.
Resistance to movement =( pressure upstream-pressure
downstream)/ length of capillaries

P1 P2

l
 Types of filtration
◼ Surface/ screen filtration ◼ Depth filtration
➢ It is a screening action by which ➢ In this slurry penetrates to a point
pores or holes of medium prevent where the diameter of solid
the passage of solids. particles is greater than that of
➢ Mechanism involved : straining the tortuous void or channel.
and impingement ➢ Mechanism : Entanglement
➢ For this, plates with holes or ➢ The solids are retained with a
woven sieves are used. gradient density structure by
➢ Efficacy is defined in terms of physical restriction or by
mean or maximum pore size. adsorption properties of medium.
Difference between surface and depth
filtration
• Surface filtration Depth filtration
◼ The size of particles retained is ◼ The size of particles retained is
slightly higher than the mean pore much smaller than the mean pore
size of medium. size of medium.
◼ Mechanical strength of filter ◼ Mechanical strength of filter
medium is less, unless it is made medium is high.
of stainless steel. ◼ It has high capacity.
◼ It has low capacity. ◼ The size of particles retained is
◼ The size of particles retained is less predictable.
more predictable. ◼ Equipment is cheaper because
◼ Equipment is expensive because ancillary equipment is not
ancillary equipment such as edge required.
clamps is required. ◼ Ex. Ceramic filters and sintered
◼ Ex. Cellulose membrane filter. filters.
Difference between Filtration and Clarification

Filtration may be defined as the separation of an insoluble

solid from a fluid by means of a porous medium that retains
the solid but allows the fluid to pass.

% of solid in filtration = more than 0.1%

% of solid in clarification = less than 0.01%

When solids are present in very low concentration (≤ 1.0 %

w/v) and is finely subdivided / amorphous / colloidal in
nature, then the process of separating them is known as
Clarification.
Problems associated with Filtration

1. Bleeding:
During filtration, solid particles pass into the filtrate
and as a result, the filtrate becomes cloudy.
Cause:
If the pore size of the filtering media is larger than the
particle size.
Remedy:
✓By decreasing the pore size
✓By providing larger sized particles
Problems associated with Filtration…….

2. Plugging:
When solid particles block the pore hardly.
Remedy:
✓ Changing the filter media
✓ Acid treatment, if there is no interaction between acid and
media
✓ By increasing pore size

3. Wedging:
When solid particles block the pore loosely that can be
removed by water jet at high speed.
Problems associated with Filtration…….

4. Shedding:
Though there is no leakage in cake and no bleeding, solid
particles appear in filtrate. (If the reason is unknown)
Cause:
May be due to collapse of certain portion of bridge of the cake.
As the cake forms, certain portion of the bridge may collapse
due to the gravitational force of the undissolved solids.
Remedy:
✓Removal of some cake after certain time.
✓Collecting the filtrate after a certain time interval rather than
at the end of the process.
✓If the particle size is uniform, shedding will not occur.
Factors Affecting The Rate Of Filtration
• The factors which affect the rate of filtration of any liquid can be
expressed by Darcy’s law which is stated below-

dv/dt – KA ΔP/ηl
Where V=volume of filtrate, t = time of filtration,
K = constant for the filter medium and filter cake,
A = area of filter medium,
ΔP=pressure difference above the filter medium and below the filter
medium,
η = viscosity of the filtrate,
l = thickness of the filter bed i.e. thickness of the filter cake and filter
medium.
 Cont…

From the Darcy’s law it is clear that the rate of filtration

depends upon a no of factors and not only the liquid which is
undergo for filtration.
The factors which governs the rate of filtration are-

1.Area of filter surface,

2.Particle size of the solids to be removed,
3.Pore size of the filter media,
4.The resistance of the filter cake and filter media,
5.Viscosity of the liquid to be filtered,
6.Temperature,
7. Pressure difference across the filter.
 Factors influencing Filtration
1. Effect of Pressure (↑): Usually compressible cakes have a critical
pressure above which flow rate decreases. Incompressible ones increase
flow rate with increase in pressure.
However in the early stages of filtration, there should be
less pressure differential otherwise it will clog the pores of
the filter medium.
Increasing pressure to augment the rate of filtration is a
common practice for Industries as most of their equipments are
made of SS, that can withstand high pressure.

2. Effect of Vacuum (↑): Reducing the pressure underneath the filter

media increases the rate of filtration.
This is a common procedure in the laboratories as most of the
equipments are made of glass. So, there is no chance of
explosion.
 Factors influencing Filtration…….

3. Cake Thickness (↓): Flow rate is inversely proportional to the amount of

cake deposited.

4. Effect of Viscosity (↓): Flow rate is inversely proportional to the

filtrate viscosity. High viscosity can be decreased by diluting it
with a low viscosity solvent.

5. Effect of Temperature (↑): Viscosity decreases markedly with increase

in temperature. Higher temperatures thus permit higher filtration rates.

6. Effect of Particle Size (↑): Decreased particle size results in lower flow
rate.
 Factors influencing Filtration…….
7. Effect of Particle Shape : Due to less inter particular space, spherical
particles give slow filtration than irregular one.

8. Effect of Type of Filter Medium : Open weave reduces plugging, again

tight weave reduces bleeding. Thus a balance is necessary. After a small
thickness of cake is formed, bleeding stops and fine particles are caught in
the cake.

9. Effect of Solid Content (↓): Rate of filtrate flow is inversely

proportional to the ratio of solids to filtrate.
But the rate of cake deposition is directly proportional to this ratio.

10. Area of filter media (↑): Rate of filtration is directly proportional to

area of filter media.
Filter Media
In most filtrations the medium does not do the actual filtering but
merely acts as a support for the cake of solids.
Filter medium should be selected primarily for its ability to retain the
solids without plugging and without bleeding at the start of filtration.
The surface or medium upon which solids are retained in the process
of filtration is known as filter media.
An ideal filter media should have the following properties:
a) It should be chemically inert.
b) It should have high retention power for the solids but
should allow the maximum passage of the liquids.
c) It should have sufficient mechanical strength to
withstand filtration pressure.
d) It should absorb negligible amounts of dissolved
material.
e) It should be resistant to corrosive action of the liquid.
f) Smooth surface for easy discharge of cake.
 Filter Media Examples:
1) Woven materials made form Cotton, Wool, Linen, Jute, Silk. Synthetics are
more chemically resistant. Cotton has a low cost, available in a wide variety of
weaves, attacked by all mineral acids and many organic acids, also attacked by
strong alkalis. Cotton's operating temperature should be kept below 200ºF.
2) Perforated metal sheet such stainless steel plates with pores (Edge Filter)
3) Bed of granular solid built up on a supporting medium. Examples include
Sand, Gravel, asbestos etc.
4) Prefabricated porous solid unit: Prefabrication of porous solid units into a
single unit are becoming popular now-a-days due to convenience of use.
Examples include Sintered glass, sintered metal, porous plastics are
commonly used for fabrication.
5) Membrane filter media: They can be either surface cartridges or depth
type cartridges.
Types of filter media
Surface area of filter medium
Rate of filtration:
• Inversely proportional to specific surface of filter bed
(According to K-C equation).
• Directly proportional to surface area of filter medium
(According to Darcy’s equation)
• Rate can be increased either using large filter or
connecting a number of small units in parallel.
• Filter press works on principle of connecting units in
parallel.
Filter Aids
◼ The objective of filter aid is to prevent the medium from becoming
blocked and to form an open, porous cake, hence, reducing the
resistance to flow of the filtrate.
◼ Filter aid forms a surface deposit which screens out the solids and also
prevents the plugging of supporting filter medium.
Characteristics of filter aids:
◼ Chemically inert and free from impurities.
◼ Low specific gravity, so remain suspended in liquids.
◼ Porous rather than dense, so that pervious cake can be formed.
◼ Recoverable.
Disadvantages:
◼ Remove the coloured substances by absorbing them.
◼ Sometimes active principles such as alkaloids are absorbed on filter aid.
◼ Rarely, filters are source of contamination such as soluble iron salts,
which can provoke degradation of sensitive ingredient
 Selection of Filtration Equipment
There are a number of product related factors that should
be considered when selecting a filter for a particular
process. These include:

◘ Chemical nature of the product:

Interactions with the filter medium may lead to leaching of the
filter components, degradation or swelling of the filter medium
or adsorption of components of the filtered product on the filter.
All of these may influence the efficiency of the filtration process
or the quality of the filtered product.

◘ Volume to be filtered and filtration rate required:

These indicate the size and type of equipment and the amount
of time needed for the filtration process.
 Selection of Filtration Equipment……
◘ Operating pressure needed:
This is important in governing the filtration rate and influences
whether a vacuum filter is appropriate. High operating
pressures require that the equipment be of sufficient strength
and that appropriate safe operating procedures be adopted.

◘ Amount of material to be removed:

This will influence the choice of filter, as a large 'load' may
require a filter where the cake can be continuously removed.
 Selection of Filtration Equipment……
◘ Degree of filtration required:
This indicates the pore size of membrane filters or the filter
grade to be used. If absence of microbes is required then
the equipment should itself be capable of being sterilized,
and must ensure that contamination does not occur after the
product has passed the filter .

◘ Product viscosity and filtration temperature:

A high product viscosity may require elevated pressures to
be used. The incoming formulation can be heated, or steam-
heated jackets be fitted to the equipment. Care should be
taken to ensure the equipment seals etc. can operate at
elevated temperatures.
Sand Filter

• It is the oldest type of large-scale

filter. It is a Gravity Filter.

• Water passes first through about 36

inches of sand, then through a layer
of gravel, before entering the
discharge drain.

• The sand removes particles from the

water through adsorption and
straining.

• It is a very slow filter though very

economic and easy to construct.

• Another disadvantage of this filter is

chances of microbial contaminations
that may come from the sand. To
remove this problem, the sand may
be boiled before using.
 Plate and Frame Press

It is a pressure filter. Super atmospheric pressure is used to run this

machine.
1. This press is made up of two basic units – (a) Plate and (b) Frame.
2. Filter cloth is used as filter medium between the two units. The
frame is opened with an inlet.
3. Plate and frame presses may be of considerable size, with up to 60
chambers.
4. The plate has also an outlet for the filtrate.
5. The slurry enters the frame (marked by two dots).
6. The filtrate passes through the filter medium onto the surface of
the plate (marked by one dot).
7. The solids form a filter cake in the frame. The thickness of the
cake is half of the frame thickness as filtration occur on each side
the frame. Two cakes are formed in the same frame and they meet
eventually in the centre of the frame.
 Plate and Frame Press……….

8) The filtrate then drains down the surface of the plate and escapes
from the outlet. So, Filtrate is collected on the plates.
9) Filtration is continued until the frame is filled with filter cake.
10) When the process is stopped, the frame emptied and the cycle re-
started.
Diagram
Assembly of plate and frame filter
Working of Plate and frame filter press,
◼ Working can be divided into two
steps-
1. Filtration operation
2. Washing of cake (if desirable)

◼ Filtration operation

Frame- marked by 2 dots

Plate – marked by 1 dot
Washing operation
◼ When washing of cake is also required modified plate and frame
filter is used.
◼ For this purpose an additional channel is included called as
washing plate and are identified by 3 dots.
◼ In the half of the washing plate, there is a connection from wash
water cannel to the surface of plate.
◼ The sequence of arrangement of plates and frames can be
represented by dots as 1.2.3.2.1.2.3.2.1 so on (between 1 and 1,
2.3.2 must be arranged.
Diagrammatic procedure
Plate and Frame Press……….
Plate and frames may be made of various-
a) Metals (resistance to corrosion): usually made of
aluminium alloy. Sometime they are made sterilizable.
b) Non-metals ( e.g. reinforced plastics)

The mechanism of filtration of this type of filter is Surface

Filtration. That is why when cake fills the frame completely, it is
necessary to stop the operation and remove those cakes.

Several feed and discharge systems are possible:

✔Bottom feed and Top discharge
✔Top feed and Bottom discharge
✔Double feed and Double discharge
• Special provisions:
• Any possible contamination can be observed by passing the
filtrate through a glass tube or sight glass from the outlet on
each plate.
• This permits the inspection of quality of filtrate. The filtrate
goes through the control valves to an outlet channel.
• The filtration process from each plate can be seen.
• In the event of broken cloth, the faulty plate can be isolated,
and filtration can be continued with one plate less.
• Uses:
• Sterile filtrate can by obtain by using asbestos and cellulose
filter sheet (for this, whole filter press and filter medium have
been sterilized previously).
• Filtration of viscous liquid can also be done by incorporating
heating/cooling coils in the press
.
Advantages
1. Cast iron – for handling common substances.
2. Bronze - for smaller units.
3. Stainless steel – contamination can be avoided.
4. Hard rubber and plastic- used where metals must be avoided.
5. Wood- for lightness though it must be kept wet.
6. Provide large filtration area in relatively small floor space.
The capacity being variable according to thickness of frames
and number used.
7. Sturdy construction permits the use of considerable pressure
difference. (2000 Kilopascals normally used)
8. Efficient washing of cake is possible.
9. Operation and maintenance is easy.
10. It produce dry cake in form of slab.
Disadvantages
1. It is a batch filter, so it is a time consuming.
2. The filter press is an expensive filter, the emptying time,
the labour involved, and the wear and tear on the cloths
resulting in high costs.
3. Operation is critical, as the frames should be full,
otherwise washing is inefficient and the cake is difficult to
remove.
4. The filter press is used for slurries containing less about 5
% solids
5. In view of the high labour costs , it is most suitable for
expensive materials e.g. the removal of precipitated
proteins from insulin liquors.
Filter leaf
Principle:
◼ It is an apparatus consisting of a longitudinal
drainage screen covered with a filter cloth.
◼ The mechanism is surface filtration and acts as sieve
or strainer.
◼ Vacuum or pressure can be
applied to increase therate of filtration.

Use:
◼ Use for the filtration of slurry which do not contain
high solid content, about 5%, i.e. dilute suspensions.
Diagram
Working:
1. The filter leaf is immersed in the slurry
2. Vacuum system is connected to the outlet
3. The slurry passes through the filter cloth
4. Finally filtrate enters the drainage canal and
goes through the outlet into receiver
5. Air is passed to flow in reverse direction which
facilitates removal of cake
Advantages

1. Simplest form of filter used for batch process.

2. Several units can be connected in parallel to increase the
surface area of filtration.
3. Pressure difference can be obtained either with vacuum or
using pressure up to the order of 800 kilopascals.
4. Labour costs for operating the filter leaf are fairly
moderate.
5. The efficiency of washing is high.
6. The slurry can be filtered from any vessel.
7. The cake can be washed simply by immersing the filter in
a vessel of Water.
Sweetland filter (variant of filter leaf)
◼ An alternative method is to enclose the filter leaf in a
special vessel into which the slurry is pumped under
pressure.
◼ A number of leaves are connected to a common outlet,
to provide a large area for filtration.
Metafilter

• Principle:
◼ Mechanism is surface filtration.
◼ In this, metal rings contain semicircular projections,
which are arranged as a nest to form channels on
the edges.
◼ This channel offers resistance
(strainer) to the flow of solids (coarse
particles).
◼ The clear liquid is collected into receiver from the
top.
Diagram
Working
1. Filters are placed in a vessel
2. Slurry is pumped under pressure or occasionally by
applying reduced pressure to the outlet side
3. Slurry passes through the channels formed on the edges
between the rings
4. The clear liquid rises up and collected from the outlet
into receiver
5. For separation of fine particles, a
bed of suitable materials such kieselguhr is
first built up.
7. The pack of rings serves essentially as a base on which
the true filter medium is supported.
Uses

◼ Metafilters can be used for-

1. Clarification of syrups
2. Filtration of injection solutions
3. Clarification of insulin liquors
4. Filtrationof viscous liquids can be
achieved by applying pressure.
Advantages
◼ Can be used under high pressures, without any danger of
bursting the filter medium.
◼ Running cost are low, as separate filter medium is not used.
◼ Can be constructed from a material that can provide excellent
resistance to corrosion and avoid contamination of sensitive
products.
◼ It is extremely versatile filter because fine as well as large both
type of particles can be separated.
◼ Removal of cake can be carried out by simply back-
flushing
with water.
◼ Change over from one batch to another or one product to
another is easy.
◼ Sterile products can be handled.
Cartridge filter
Principle:
◼ It is a thin porous membrane in which pre filter and membrane
filter are combined in a single unit.
◼ The filtration action is mainly sieve like and particles are retained
on the surface.
Working and uses of Cartridge filter

Working:
1. Slurry is pumped into cartridge holder
2. It passes through cartridge filter unit by
straining
3. The clear liquid passes through the center
4. Moves up to collect through outlet

Uses:
◼ Particularly useful for preparation of particulate free
solutions for parenterals and ophthalmic uses.
◼ This filter holder will process 1000 – 15000
litres of sterile solution per hour.
Cartridge filter
Advantages:
◼ Autoclaving can be done for sterile operations due to stainless
steel construction.
◼ Cartridge with self cleaning devices are advantageous.
◼ Rapid disassembling as well as reusing of filter medium is
possible.
◼ Cartridge are not brittle, when they are dry.
◼ Used as in-line continuous filtration, which reduces handling of
solutions. It minimize chances of contaminations.
Disadvantages:
◼ A number of manufactures provide the components, which are
generally not interchangeable between suppliers.
◼ Cost of disposable elements offsets the labour saving in terms
of assembly and cleaning of cartridge clarifiers.
Rotary drum filter
• Principle:
◼ Slurry filtered through sieve like
mechanism on the rotation drum surface, under the
condition of vacuum.
◼ In addition compression, drying (using hot air), and
removing the filter cake (using knife) are possible.
◼ Uses:
1. The rotary filter for continuous operation on large
quantities of slurry.
2. Suitable for slurry contains considerable amounts of
solids in the range 15-30%.
3. Examples of pharmaceutical application include
4. the collection of calcium carbonate, magnesium
carbonate, and starch.
5. The separation of the mycelium from the fermentation
liquor in the manufacture of antibiotics.
Diagram
 Working
1. The drum is dipped into the slurry and vacuum applied
to the outlet, which is connected to the filtrate receiver.
2. When the cake has formed, the cake drained or
partially dried by vacuum.
3. The drum is sprayed with water to wash the cake.
4. Retaining the vacuum connection drains the cake and
produces partial dryness then, removed by a doctor
knife.
5. When the solids of the slurry are too much that the
filter cloth becomes blocked with the particles, a
pre-coat filter may be used.
6. A pre-coat of filter aid is deposited on the drum
prior to the filtration process.
Advantages

1. The rotary filter is automatic and is continuous in

operation, so that the labour costs are very low.
2. The filter has a large capacity , so it is suitable for
the filtration of highly concentrated solutions.
3. Variation of the speed of rotation enables the cake
thickness to be controlled.
4. Pre-coat of filter aid could used to accelerate the
filtration rate.
5. Filter has large surface area.
Disadvantages
1. The rotary filter is a complex piece of equipment , with
many moving parts and is very expensive,.
2. In addition to the filter itself, some accessories are
connected e.g., a vacuum pump, vacuum receivers,
slurry pumps and agitators are required .
3. The cake tends to crack due to the air drawn through by
the vacuum system, so that washing, and drying are not
efficient.
4. Being a vacuum filter, the pressure difference is limited to 1
bar and hot filtrates may boil.
5. It is suitable only for straight- forward slurries