CLARIFICATION

processes that involve the removal or separation of a solid from a fluid, or fluid from a
fluid
fluid liquids or gases
reasons: 1) to remove unwanted solid particles
2) to collect the solid as the product itself

Filtration
Types of Filtration
1) Solid/fluid filtration
separation of an insoluble solid from a fluid
means of a porous medium that retains the solid but allows fluids to pass
most common type
1.1) Solid/liquid filtration
improvement
of
appearance
of
recovery of desired solid form a
solutions
suspension or slurry
give a sparkle or brightness
extraction of vegetable products
clarifying a product
sterilization processes involving heat
removal of potential irritants
are not appropriate
eye drop preparations
detection of microorganisms present in
solutions applied to mucous
liquids
membranes
assess
the
efficiency
of
production of water of appropriate
preservatives
quality
1.2) Solid/gas filtration
removal of suspended solid material from air to supply air of the required standard
processing equipment: fluidized-bed processors, film-coating machinery, bottlecleaning equipment
manufacturing areas: area for sterile products
to prevent material being vented to the atmosphere
filtering exhaust air
2)

Fluid/fluid filtration
filter turbidity from spirits + aqueous-based formulations
filter compressed air for pharmaceutical processes to ensure removal of oil or water
droplets

Mechanism of filtration
Straining/sieving
pores in the filter medium: smaller than material to be removed
membrane filters filtration occurs at the surface of thin filter (100m)
straining mechanism for small volumes to be filtered or low contaminant level
formulations
bacteria & fibre removal from parenteral preparations
Impingement

depth filters sufficiently thick filter media

material not trapped by first fibre will be removed by a subsequent one

streamline flow of fluid through filter

turbulent flow will carry particles past the fibres

mainly used for removing material from gases
Attractive forces
electrostatic forces exert hold on particles
electrostatic precipitator free air from dust particles
Autofiltration
filter cake (filtered material) acts as its own filter medium
used by metafilter

Factors Affecting the Rate of Filtration

Darcys equation
Methods to increase filtration rate
increase available area for filtration
directly proportional to volume of filtrate flowing
increase pressure difference across the filter cake
decrease filtrate viscosity
governed by Poiseulles Law
decrease thickness of filter cake
increase permeability of cake
filter aids are included in the formulation to be filtered
more open, porous nature cake
filter aids: 1) diatomite (form of diatomaceous earth)
for filtration of penicillin &
2) perlite (type of volcanic glass)
streptomycin
Filtration Equipment
1) Gravity filters rely solely on gravity
generate low operating pressures
limited use on a large scale basis
simple & cheap; for laboratory filtration
2) Vacuum filters
Rotary vacuum filter
two concentric cylinders divided into septa by radial partitions
outer cylinder: perforated, covered with filter cloth
cake compression rollers: to improve washing & draining efficiency
string discharge filter: to filter fermentation liquor in manufacturing of antibiotics
for slurry with 15-30% content of solids
adv: 1) automatic & continuous in operation; very low labour costs
2) large capacity filter
3) rotational speed variation enables control of cake thickness
disadv: 1) very expensive
2) cake tends to crack due to inefficient washing & drying
3) limited pressure difference
4) suitable only for straightforward slurries
pharmaceutical application:
1) collection of CaCO3, MgCO3, starch
2) separation of the mycelia from fermentation liquor in the manufacture of
antibiotics
3) Pressure filters
Metafilter
grooved drainage rod packed with stainless steel metal rings
for separating coarse particles
need of a filter aid to separate finer particles

small surface area clarify liquids with low contaminant level

suitable for viscous liquids
adv: 1) use of high pressures without danger of bursting the filter medium
2) no filter medium; very economical
3) excellent resistance to corrosion; avoid product contamination
4) possible to remove very fine particles; possible to sterilize a liquid
disadv: 1) very expensive
2) cake tends to crack due to inefficient washing & drying
3) limited pressure difference
4) suitable only for straightforward slurries
pharmaceutical application:
1) clarification of syrups, injection solutions, intermediate products like
insulin liquors
Cartridge filters
possess very large filtration area
easy & relatively cheap to operate
cylindrical cartridge containing highly pleated material (PTEE or nylon) or stringwound
filter cartridges are disposable
Cross-flow microfiltration
form membrane filters within hollow fibres
membrane: consist of polysulphone, acrylonitrile, or ployamide
lumen of each fibre is small (1-2m)
permeate ( or filtrate) flows radially
adv: minimal blocking of membranes due to high fluid velocity & turbulence
pharmaceutical application:
1) fractionation of biological products (i.e. prepare concentrated purified
albumin by removing water & alcohol form blood plasma)
2) recovery of antibiotics from fermentation media

Centrifugation
Centrifugal force provide the driving force for filtration process
replace gravitational force in sedimentation process

Centrifuges separate solid from a liquid

solid forms a plug at the bottom
Principle: more efficient to increase the centrifuge speed to increase the centrifugal
effect
Industrial Centrifuges
1) Perforated-basket centrifuges

or centrifugal filters

stainless steel basket lined with a filter cloth; rotates at a speed of <25s -1

product enters centrally then thrown out radially by centrifugal force

filtrate is held against & forced through the filter cloth

filtrate removed via the liquid outlet

for separating crystalline materials from the preparation liquor

for removing precipitated proteins from insulin

adv: compact & sufficient; cheaper to run

product has a low moisture content (2% w/w)

2) High-speed mixer/granulators
cylindrical bowl
product enters at the bottom
to separate immiscible liquids

good for separating difficult solids

uses:
liquid/liquid separation (for antibiotic manufacturing & purification of oils from
natural source)
remove very small particles
remove compressible solids or slimy solids
separate blood plasma from whole blood
separate different particle size fractions
examine stability of emulsions
adv: compact; high separating efficiency
disadv: limited capacity; complicated to construct to achieve required speed & minimize
vibration