Filtration and clarification

Filtration: The separation of solid from a fluid by means of a porous medium that retains the
solid but allows the fluid to pass.
Clarification: This term is applied when solid do not exceed 1.0%
Cake Filtration: If recovery of solid is desired, the process is called cake filtration or When the
solid concentration in the suspension is sufficiently high, solids will bridge over the entrance of
filter medium pores.
Filtrate: The clear liquid passing through the filter is the filtrate.
Straining: When the object of filtration is to remove large visible particles by using coarse
filtering medium such as muslin and cotton wool, This process is called Straining.
Theory of Filtration: The flow of solid is resisted by the filter medium while the liquid is
allow to pass. As the filtration proceeds the retention of the solid on the filter media goes on
increasing which acts as a secondary and some times more efficient filtering media.
However, it can also act as a resistance medium. An expression of this changing resistance
involves a material balance as well as factors expressing permeability or coefficient of
resistance of the continuous expending cake.
The rate is defined as Poiseuille’s eq

Where V = volume of filtrate, T = time, A = filter area, P = total pressure drop through cake
and filter medium, μ = filtrate viscosity, α = average specific cake resistance, W = weight of
dry cake solids, R = resistance of filter medium and filter.
The rate of filtration can be expressed as
Filter Media: The surface upon which solids are deposited in a filter is called the Filter
medium. They should be
• Chemically inert.
• High retention power.
• Sufficient mechanical strength.
• Absorbs negligible amount of material.
• Resistant to the corrosive action of liquid.
Selection of filter media depends on followings: Size of particle to be filtered. Amount of
liquid to be filtered. Nature of product to be filtered.
Filter paper: Filter paper is a common filter medium since it offers controlled porosity,
limited absorption characteristic, and low cost. It has different grades and qualities, different
pore size such as coarse medium and fine.
Disadvantages: They shed very fine particle to the filtrate. Absorb small quantity of liquid.
Woven Material: Cotton silk, wool, nylon. It is used as backing for paper or felts in plate and
frame filter. Nylon cloth is superior to the cotton cloth since it is not affected by molds, fungus and
bacteria and provide smooth surface for cake. It has negligible absorption properties. It is extremely
strong as compared to cotton cloth. Both of these can be sterilized so can be used for aseptic
filtration.
Woven wire cloth: Made from stainless steel. Resistant to plugging and easily cleaned. Long
lasting. Resistant to the chemicals. Usually used with filter aids. Mostly used in filling line to avoid
the foreign material.
Nonwoven filter media includes felts, bonded fabrics and kraft papers.
Felts: is fibrous mass of mechanically interlocked fibers to yield specific pore size. High flow rate
with low pressure drop is a primary characteristic. Good for gelatinous and fine particulate matter.
Kraft papers: is a pharmaceutical standard, use in plate and frame filters and horizontal plate filters.
Controlled porosity, limited absorption characteristic and low cost making it disposable. Support of
cloth or wire mesh is imp to give strength.
Cotton Wool: Commonly used. Small tough of cotton wool placed in the neck of funnel.
Glass wool: Use for filtering highly corrosive chemicals. May contaminate the filtrate with glass
fiber.
Asbestos: Also used for filtering the corrosive liquid. Used in gravimetric analysis for collecting
fine precipitates.
Membrane Filter: These are very common among the ultrafiltration methods. Mostly for sterile
solutions. Made up of cellulose, Polyvinylchloride, Nylon and other cellulose derivatives. They are
very fine having a very vide range of pore size from 8µ down to 0.22µ. Uniform pore size, forty
times faster than other media, often prefiltration is required.
Cartridge units: economical, convenient, range
100 microns to less than 0.2 micron. May be
surface or depth filter with plastic or metal
structural hardware. Can have synthetic or
natural fibres, cellulose ester and fibre glass,
Teflon, nylon or ceramics for disposable
cartridges.
Sintered Glass: Made form borosilicate glass. Glass is powdered and sifted to produce
uniform particles. Heated and fitted in to glass funnel of suitable size and shape. Used for
filtering parenteral preparations. Useful for filtering the corrosive liquid and oxidizing
agent. Advantages Don’t shed particles. Don’t absorbs any liquid. Can be easily washed.
Surface type and depth type cartridges:
Filter aids: The substances which when added to the liquid to be filtered, reduce the
resistance of the filter cake and increase the filtration.
Properties of Filter Aids:
• Chemically inert
• Insoluble in liquids
• Form a porous cake
• Free from impurities
• Able to remain suspended in liquids
• Free from moisture
Application of filter media
Precoat: Precoat to generate a thin layer of solids on top of the filter media.
Achieved by mixing the filter aid into clear liquid or mother filtrate. Optimum conc. 0.3 – 0.6wt%
for diatomite filter aids. The precoat thickness should be thick enough to ensure that the entire
media surface is coated but thin enough so that it does not provide significant resistance to
filtration. Optimum feed flow rate of 1 GPM/ft2. Typical precoat thicknesses are in the 1- 3mm
range for polishing filtration.
There are several advantages to using precoat in a clarification processes. Use of a precoat helps
prevent the filter media from becoming clogged by the slurry fines, thus extending filter media life.
especially when filtering amorphous or slimy solids.
Precoating helps provide immediate filtrate clarity. The precoat layer acts as a depth filtration bed
which will help trap fine particles that would typically pass through the filter media. Precoat helps
filter cake solids discharge from the filter media at the end of a filtration cycle by providing a
cleavage plane from the filter media.
Body Feed: In body feed filtration applications, the filter aid is blended with the slurry
feed. The filter aid solids and the native solids continuously build a filter cake until the
maximum cake height is reached or the maximum operating pressure is reached. By adding
filter aid into the slurry feed, the resulting filter cake is more porous, allowing higher and
longer sustained flow rates. The body feed can function physically, mechanically or
chemically.
• Body feed also helps to restrict solids movement which improves filtrate clarity. The goal
of the optimal body feed concentration is to maximize the flow rate of a filtration cycle
while avoiding feeding too much filter aid solids. Using too much body feed will cause
the filter to reach the maximum filter cake height faster than necessary.
• When using a body feed without precoat, there can be an initial turbid filtrate while the
cake begins to build on the filter media. This initial turbid bypass will generally be much
shorter than what would be observed filtering the raw slurry. It is possible to recycle this
turbid filtrate back to the slurry feed tank to verify no solids bypass occurs.
Selection of filter aid by trial and error.
For pharmaceutical applications –inertness of the aid and media.
Selection of optimum temp.
Selection of filter medium: check the chemical compatibility. Filter type, cellulose,
polytetrafluoroethylene (PTFE), fiber, metal, polyvinylidene difluoride, nylon, or polysulfones
may be selected based on the chemical resistance to the most aggressive ingredient in the
liquid. For vent filters or gaseous filtration, a hydrophobic filter medium should be chosen.
The filter aid quantity can be expressed as a percentage of cake solids, a percentage of filter
aid in body mix, or the weight applied as a precoat per unit of filter area.
Filtration surface area is calculated after the filter media, pore size, required flow rate, and
pressure differentials are established. For a liquid having a viscosity significantly different
from that of water (1 cp), the clean water flow rate is divided by the viscosity of the liquid in
centipoises to obtain the approximate initial flow rate for the liquid in question.
For gaseous filtration at elevated temperature and exit pressures, the standard flow rate (20°C, 1
atmosphere) must be corrected by equation (6), the gaseous filtration flow rate formula:

where: F = corrected flow rate, F0 = standard flow rate from chart (20°C, 1 atmosphere) t =
temperature of air or gas ( 0°C), P = exit pressure (psia), ΔP = pressure drop through the system
(psi). If the pressures are expressed in kg/cm2, the term 14.7 in equation becomes 1.03.
The optimum system often requires use of a series of filters in a single multilayered filter
containing layers of various pore sizes or a prefilter followed by a final filter.
Flow rate should be determined for each case at constant pressure and after a uniform time
interval.
Nonsterile Operations: Most pharmaceutical filtrations aim for removal of particles of 3 to 5
microns or less. A nephelometer, an instrument that measures the degree of light scattering
(Tyndall effect) in dilute suspensions, is an excellent tool for assessing effectiveness in this
range. The nephelometer gives a quantitative value to the formulator's quality specification of
"sparkling clear."
The question of time for a filtration cycle is resolved by
determining total volume vs time during a test run at
pressures approximating normal operating conditions.
Plotting log total volume per unit area vs log time usually
gives a straight line suitable for limited extrapolation. If the
filter area of production equipment is fixed, the time to filter
a given batch size may be estimated. Alternately, the filter
area required to complete the process within an allotted time
period may be established.
In semicontinuous operations, decisions must be made on
length of the cycle prior to shutdown for replacement of
media. During productive time T, the filter discharges a
clear filtrate at a steadily decreasing rate. Nonproductive
time T' is required to clean the filter and replace media.
Sterile Operation: porcelain candles and asbestos pad, which requires extensive cleaning.
Membrane filters: absorption effects are negligible, no pretreatment required, can be
autoclaved or gas sterilized after assembly.
Membranes with porosity ratings of 0.2 or 0.45 microns are usually specified for sterile
filtrations. Required prefiltration. The FDA allows the use of 0.45-micron filters in cases of
colloidal solutions in which 0.2-micron filters have been shown to clog very rapidly.
Oil and viscous aqueous menstruums are heat-sterilized whenever possible. These solutions
are usually clarified through coarser, non-sterilizing membranes, preferably prior to heat
sterilization.
Air filtration: Vent filtration, Compressed air used in sterilizers, Air or nitrogen used for
product and in-process solution transfers and at filling lines. Air or nitrogen used in
fermentation
The basic elements of any sterile operation must be followed. All apparatus should be cleaned
and sterilized as a unit. Filtration should be the last step in processing, and the filter should be
placed as close as possible to the point of use of final packaging, filtration should be done at
atm pressure.
Integrity testing: Prior to filtration, the integrity test detects a damaged membrane, ineffective
seals, or a system leak.
Bubble point test: Membrane filters can be
regarded as fine, uniform capillaries. The bubble
point test is based on the fact that when these
capillaries are full of liquid, the liquid is held by
surface tension. The minimum pressure required to
force the liquid out of the capillary must be
sufficient to overcome surface tension.
Although each membrane has a specific bubble
point, which is dependent on the liquid wetting the
membrane, a test at a pressure of 20 pounds per
square inch (psi) is usually sufficient to detect
leaks.
Diffusion Test: At differential gas pressures below the bubble point, gas
molecules migrate through the water-filled pores of a wetted membrane
following Fick's Law of Diffusion. At a pressure approximately 80% of
the minimum bubble point, the gas which diffuses through the
membrane is measured to determine a filter's integrity. The flow of gas is
very low in small area filters, but it is significant in large area filters.
• Thoroughly wet the filter with appropriate test fluid.
• Slowly increase pressure on the upstream side of the filter to the
recommended test pressure provided by the manufacturer, typically at
least 80% of the minimum bubble point specification.
• Allow the system to equilibrate.
• Measure the gas flow at the outlet with an inverted graduated cylinder
or a flow meter.
A diffusional flow reading higher than the specification indicates either
• wrong pore size
• temperature other than ambient
• incompletely wetted membrane
• non-integral membrane or seal
• liquid/gas combination different than the recommended fluids
• inadequate stabilization time
Pressure hold test: The Pressure Hold Test, also known as pressure decay or pressure drop
test, is a variation of the diffusion test. In this test, a highly accurate gauge is used to monitor
upstream pressure changes due to gas diffusion through the filter. Because there is no need to
measure gas flow downstream of the filter, any risk to downstream sterility is eliminated.
Filtration Equipment and Systems: Based on type of driving force
Gravity filters:
Sand filters: The filtering medium may consist of sand or cake beds or for special purposes, a
composition containing asbestos, cellulose fibers, activated charcoal, diatomaceous earth, or
other filter aids. Small scale may use porous ceramics.
Tray and frame filters are best adapted for slow, difficult filtrations and for exceptionally soft-
or fine-grained precipitates, which clog under the slightest pressure or pass through the
openings of a cloth. Gravity bag filters also are applied to concentration of magmas, such as
milk of magnesia. More efficient methods, however, particularly with respect to space
requirements, are available. The gravity nutzch is a false-bottom tank or vessel with a support
plate for filter media. Porcelain nutzches may be used for collecting sterile crystals.
Vacuum filters are employed on a large scale, but are rarely used for the collection of
crystalline precipitates or sterile filtration system, vacuum is applied to the drum, and the fluid
flows through the continuous belt. Solids are collected at the end of the belt.
The plate and frame filter press is the simplest of all pressure filters and is the most widely
used. Filter presses are used for a high degree of clarification of the fluid and for the
harvesting of the cake. When clarity is the main objective, a "batch" mode operation is
applied.
It consists of hollow frames and solid plates. The frame is open and is used as an inlet for
the material to be filtered. Plates have grooved surface to support the filter cloth. Filter cloth
is fitted on each side of the plate. Plates and frames are placed alternatively and fitted in the
outer frame of the press. Each plate has an outlet for filtrate. Each plate acts as a single
filtration unit. The outlet of each plate is connected to a common outlet pipe.
The filtering liquid enters the frame under pressure from the feed channel. The filtrate
passes through the filter medium onto the surface of the plate. The filtrate is collected
through common outlet pipe and the cake is deposited in the frames. The process of
filtration is continued until the frame is filled with filter cake. When the process is stopped,
the frame is emptied and the cycle is restarted.
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Advantages: 1. Filtering media can be used repeatedly.
2. Filter cloth can be easily replaced.
3. Operation and maintenance is easy.
4. It requires less space .
5. Provides a large surface area for filtration
6. Efficient washing of cake is possible.
Disadvantages: 1. It is not a continuous process.
2. The process becomes costlier because a lot of labor is
required for washing and replacement of the filter cloth.
3. Leakage between the plates may take place.
4. Suitable when the slurry contain less than 5% solids.
Disc filter: The disc filter overcomes some deficiencies of the filter press, Compactness,
portability, and cleanliness are obvious advantages for pharmaceutical batch operations. The
term disc filter is applied to assemblies of felt or paper discs sealed into a pressure case. The
discs may be preassembled into a self-supporting unit, or each disc may rest on an
individual screen or plate.
With filter aids, disposal of cake and cleaning becomes time-consuming. The precoat
pressure filter is designed to overcome this objection. It consists of one or more leaves,
plates, or tubes upon which a coat of filter aid is deposited to form the filtering surface. The
filter area is usually enclosed within a horizontal or vertical tank, and special arrangements
permit discharge of spent cake by backflush, air displacement, vibration, or centrifugal
action.
This type of filter is desirable for high-volume processes.
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Cartridge Filters and Systems: Cartridge filters have an integral cylindric configuration
made with disposable or cleanable filter media and utilize either plastic or metal structural
hardware. With the discovery of strong pleatable membranes such as cellulose nitrate,
polyamide, polyvinylidene chloride, PTFE, and nylon, cartridge filters have revolutionized
the filtration industry. Cartridge filters provide maximum filtration area in the smallest
possible package, allow quick changeout of the media, and save time and money.
• Cartridge filters of different shapes, structures, forms, and sizes for. different applications
in the pharmaceutical applications. The housings for cartridge filters come in a wide
variety of configurations for both micron and submicron filtration.
• Filter media can be formed into cartridge form by either tubular-wound, string-wound, or
pleated formation. Alternate layers of filter media and separator material are rolled into a
spiral configuration, and by potting the ends of the cartridge, form the "dead-ended" or
"crossflow“ type of flow channels.
Cartridge Filters
• String-wound cartridges are the most commonly used and
inexpensive filters available. Pleated cartridges are modified
tubular configurations with a large filtration area. A single
knife-edge flat gasket may be a satisfactory seal for
cartridge filters with 1.0-micron or larger pore size. For
submicron filtration, the most satisfactory seal is an O-ring.
• The metallic edge filters, particularly those with self-
cleaning devices are excellent security filters for
suspensions that may plug or blind conventional Wire mesh.
The cartridges with Multiple-element configurations have
become the unit of choice for high-volume, sterile filtrations
and are ideal for in-line, final polish prior to bottling of bulk
parenterals.
• https://www.youtube.com/watch?v=VFw8bDzAmRI
Membrane Filters and Housings Membrane filter holders accept membranes from 13 to
293 mm in diameter. A useful rule of thumb for membrane media and holder sizes for
various volumes of low-viscosity liquid is shown in Table. Although 90- or 142-mm units
are suitable for moderate volumes, the 293-mm membrane holder is the usual production
choice for small-batch sizes. Stainless steel holders for the sterilizing filter have sanitary
connections, and the support screens are faced with Teflon to permit autoclaving with the
membrane in place. Special compatibility problems may require polyvinylchloride holders
with stainless steel supports, or units that have only Teflon and polypropylene contact parts.
Cake Filtration: “plate and frame press” and “precoat pressure filters”, batch operation
Drum filteration: For large-scale operations, continuous vacuum filters are most widely used. The
rotarydrum vacuum filter is divided into sections, each connected to a discharge head. The slurry is
fed to a tank in which solids are held in suspension by an agitator. As the drum rotates, each section
passes through the slurry, and vacuum draws filtrate through a filter medium at the drum surface.
The suspended solids deposit on the filter drum as a cake, and as rotation continues, vacuum holds
the cake at the drum surface. The cake is washed and dried as it moves toward the discharge point. It
may be scraped from the drum or it may be supported by strings until it breaks free under
gravitational forces. Many variants of the basic design are needed to accommodate differences in
cake formation, drying rates, and discharge properties.

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Filtering centrifuges: This type of filtration is
particularly advantageous when very fine particles are
involved. This device is fitted with a perforated basket,
which supports the filter media. The basket revolves
inside the casing. Slurry is sprayed into the basket, in
which centrifugal action forces the filtrate through the
media on which the cake deposits. Continuous discharge
of solids is possible, but batch units that require shutdown
for removal of solids are also common. Whenever solids
recovery is the primary goal, centrifuges must be
considered as an alternative to filtration.
Ultrafiltration: Ultrafiltration membrane retains most macromolecules while allowing smaller
molecules and the solvent to pass through the membrane, even though the membrane is not rated
as absolute. The difference between microfiltration and ultrafiltration is significant. The former
removes particulates and bacteria; the latter separates molecules. Application of hydraulic
pressure reverses the normal process of osmosis, so that the membrane acts as a molecular screen
through which only those molecules below a certain size are allowed to pass.
Ultrafiltration is similar in process to reverse osmosis; both filter on the basis of molecular size.
Ultrafiltration is different from reverse osmosis in the sense that it does not separate on the basis
of ionic rejection. Dialysis and ultrafiltration are similar in the sense that both process separate
molecule, but ultrafiltration is different in that it does involve the application of pressure.
The selectivity and retentivity of a membrane are characterized by its molecular weight cutoff.
configuration and shape of the molecule and its electrical charge plays important role.
Applications in the pharmaceutical industry are predominantly in the concentration of heat labile
products, such as vaccines, virus preparations, and immunoglobulins. Ultrafiltration also has been
use to recover antibiotics, hormones, or vitamins from fermentation broths, to separate cells from
fermentation broth, to clarify solutions, and to remove low-molecular-weight contaminants prior
to using conventional recovery techniques. The most important application of ultrafiltration is the
removal of pyrogens.