Filtration and clarification

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Definition

 Filtration : It may be define as a process of separation of solids from a fluid by

passing the same through a porous medium that retains the solids but allows the fluid
to pass through.
 Can be achieved by using filter media like Filter paper/leaf
 Clarification: When solid are present in very low concentration, i.e., not
exceeding 1.0% w/v, the process of its separation from liquid is called
clarification.
 Can be achieved by doing Filtration or centrifugation.

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Cont….
 Meta Filter is used for the clarification of syrup and
Elixirs
 Ultra-filtration: Separation of inter-micellar liquid
from solid by the use of pressure on a semi permeable
membrane
 Slurry: The suspension of solid and liquid to be
filtered.
 Filter medium: The porous medium used to retain
the solids
 Filter cake: The accumulation of solids on the filter
medium
 Filtrate: The clear liquid passing through the filter
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Filtration process

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Mechanism of filtration
Methods Mechanism
Straining/sieving Similar to sieving, i.e. particles of larger size can‘t pass through
smaller pore size of filter medium
Impingement/inertial Solids having the momentum, move along the path of streaming flow
impact and strike (impinge) the filter medium. Thus the solids are retained on
the filter medium
Entanglement/Diffusion 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. Very effective to remove small particles.

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

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Applications of filtration
 Production of sterile products:- (HEPA- high efficiency particulate air filter) filters
(or) laminar air bench provide sterile environment during manufacture of sterile
products.
 Bacteria proof filters are used for filtration of thermolabile substances where
heat sterilization is not applicable.
 Production of bulk drugs:- Filtration is an essential step in the removal of
impurities from the products.
 Production of liquid orals:- Filtration is very important in the production of
liquid orals and other for obtaining clear solution.
 E.g. in aromatic water preparations, syrups, elixirs and eye drops, where removal of
foreign impurities is very important

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Filter Media
 Responsible for the collection of solids and provide the support to the filter cake.
Properties of ideal filter medium: It should-
 Be capable of delivering a clear filtrate at a suitable production rate
 Have sufficient mechanical strength.
 Be inert.
 Retain the solids without plugging at the start of filtration.
 Not absorb, dissolve material and contaminant the material (shed very fine particle).
 Sterile filtration imposes a special requirement since the pore size must not exceed the
dimension of bacteria or spores.

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Types of Filtration
Surface/ screen filtration
 It is a screening action by which pores Depth filtration
or holes of medium prevent the passage  In this slurry penetrates to a point where the
of solids. diameter of solid particles is greater than
 Mechanism involved : straining and that of the tortuous void or channel.
impingement  Mechanism : Entanglement

 For this, plates with holes or woven  The solids are retained with a gradient
sieves are used. density structure by physical restriction or
by adsorption properties of medium.
 Efficacy is defined in terms of mean or
maximum pore size.

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 Difference between Surface and Depth Filtration
Surface/ screen filtration Depth filtration/deep bed filtration

The size of particles retained is slightly higher than The size of particles retained is much smaller than the mean
the mean pore size of medium. pore size of medium.

Mechanical strength of filter medium is less, unless it Mechanical strength of filter medium is high
is made of stainless steel.
Mechanism involved : straining and impingement Mechanism : Entanglement
It has low capacity High capacity
Size of particles retained is more predictable The size of particles retained is less predictable
Ex. Cellulose membrane filter, nylon and polyvinyl Fibrous medium: e.g. Cotton Wool fibers, Glass wool ,
chloride Asbestos. Porous medium: It is made up of sintered
glass, metal or porous plastic or porous ceramic.
Mainly used to remove microorganism and very fine
particles from ophthalmic solution and parenteral
products.

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 Surface/ screen filtration

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Theories of Filtration
 The flow of 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
 The rate of filtration may be expressed as volume (liters) per unit time (dv/dt).
 Driving force = pressure upstream – pressure downstream
 Resistance is not constant.
 It increases with an increase in the deposition of solids on the filter medium.
 The rate of flow will be greatest at the beginning of filtration process, since the
resistance is minimum.
 After forming of filter cake, its surface acts as filter medium and solids
continuously deposit adding to thickness of the cake

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 Poiseulle’s Equation  Factors affecting the rate of
V filtration
 Where, V= rate of flow, ie, volume of liquid
flowing in unit time,
 Volume of filtered material (V; m3
 ∆P=pressure difference across the filter Pa,  The area available for filtration (A;
 r=radius of the capillary in the filter bed, m,
m2 ),
 L=thickness of the filter cake (capillary length),
m,
 The pressure difference (P; Pa)
 ɳ= Viscosity of the filtrate, Pas  The viscosity of the fluid passing
 Darcy's Equation through the filter,
 The factors influencing the rate of filtration  The thickness of the filter medium
has been incorporated into an equation by and any deposited cake .
Darcy, which is
V=KA ∆𝑷/ ɳL
where, K=Permeability coefficient of the cake
A= Surface area of porus bed(filter medium)
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Factors influencing filtration

 Properties of liquids
 Density
 Viscosity
 Cohesiveness
 Properties of solid
 Particle shape  Rigidity or compressibility of solid
 Particle size under pressure
 Particle charge  Tendency of particle to flocculate or
 Density adhere together
 Particle size distribution  Properties of solid in slurry

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Filter –aids
 The substances which when added to the liquid to be filtered, reduce the
resistance of the filter cake and increase the filtration.
 The usual concentration is up to 5%
 They increase the porosity of filter cake and prevent the blocking filter medium
 Eg. Talc, Charcoal, Asbestos, Bentonite

How Filter –aids can used

1. Pre-coating technique: by forming a pre-coat over the filter medium by filtering a
suspension of the filter aid.
2. Body- mix technique: A small proportion of the filter aid (0.1-0.5 %) is added to the
slurry to be filtered

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Classification of the basis of Scale
1. Laboratory scale filtration
 Funnel and Filter paper
 Buchner funnel and filter paper
 Sintered glass filter
 Seitz filter
 Membrane filter
2. Industrial filters
 Plate and frame filter press
 Chamber filter
 Leaf filters
 Rotary drum filter
 Edge filters e.g. Meta filter
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Laboratory scale filtration
 Buchner funnel and filter paper

 Made of porcelain, but glass and plastic funnels are also available.
 For a funnel with a perforated plate, filter medium in the form of filter
paper is placed on the plate, and the filter paper is moistened with a liquid to
prevent initial leakage.
 The liquid to be filtered is poured into the cylinder and drawn through the
perforated plate/fritted glass disc by vacuum suction.
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In large scale:
High Efficiency Particulate Air (HEPA)
 HEPA is a type of highly efficient filtration media that removes
microscopic particles from air which passes through the filter
 The most efficient HEPA filter removes 99.7% of particles with a size of
(0.3µm) that enter the filter.
 Ultra-HEPA filters typically remove at least 99.999% of particles down to 0.1
micrometers (µm) in size

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 Crystallization

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Crystallization
 Formation of solid particles within a homogeneous phase.
 Spontaneous arrangement of the particle into a repetitive order i.e. regular
geometric patterns.
 Crystallization is a chemical solid–liquid separation technique, in which
mass transfer of a solute from the liquid solution to a pure solid.
 In the crystallization from solution, two phase mixture of mother liquor (solution
body) and crystals of all size is termed as magma

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Objectives and applications
1. Purification of Drugs: remove the impurity from pharmaceuticals by re-crystallzation
process.
2. Better processing characteristics: improve the Micrometrics such as compressibility and
wettability.
3. Ease of handling: easy storage and transportation
4. Better chemical stability: e.g. crystalline amitriptyline and crystalline penicillin G is more
stable than respective amorphous form
5. Improved bioavailability: Crystalline penicillin G is least degraded in to as compared to
amorphous form.
6. Sustained release formulation: protamine zinc insulin in crystalline form is slowly
released at site of action than normal form

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Characteristics of crystal
1. Crystal lattice
2. Crystal habit
3. Crystal system or forms
1. Crystal and Crystal Lattice
 Crystal are the solid particle formed by the solidification process under suitable
environment in which structural units are arranged by a fixed geometric pattern or lattice.
 Crystal lattice or space lattice: Regular (an orderly internal) arrangement of constituent
particles in 3 D or Regular arrangement of point in 3D.

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2. Crystal Habit:
 External shape of an individual crystal. Crystal is a polyhedral solid, with a
number of plan surfaces depending upon the faces, crystal habit may be
 Columnar (Prismatic): Rod like. Eg. Fludrocortisone acetate

 Blade: long, thin and flat particle. Eg. Resorcinol

 Plate: flat particle of similar length and width. Eg. Naphthalene

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 Tabular: Flat particle of similar length and width but processing greater thickness
(height). Eg. Tolbutamide

 Equant: Particle of similar length, width and thickness Eg. Sodium chloride

 Acicular: Needle like prism E.g. Nalidixic acid

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3. Crystal forms or crystal system:

 A finite number of symmetrical arrangement are possible for a crystal lattice and
these may termed as crystal system.
 A chemical substance may exists more than one crystalline form is called
polymorphs and these phenomenon is called polymorphism
 Eg. chloramphenicol palmitate (3 forms), cortisone acetate (5 forms, 4 are
somewhat unstable as compared to V one), tetracyclines (Several forms),
sulfathiazole (three form, one 2D and rest of two 3D) and paracetamol (three form).
 It May be
 Enantiotropic: reversibly changes from one form to another by temp & pressure eg
sulphur

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Crystal forms ….

 Monotropic: unstable at all temp & pressure eg. Glyceryl monostearate

 Polymorph differ each other in their physical characters like solubility, MP,
density, hardness, compression characteristics.
 Identified by XRD, DSC.
Depending upon stability polymorph may be
a. Stable polymorphs has lower energy state, higher M.P. and least aqueous
solubility.
b. Metastable polymorphs has higher energy state, lower M.P. and higher
aqueous solubility.

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 Crystal forms ….
 Metastable form are thermodynamically unstable. Upon storage metastable my
converted to stable e.g. Cortisone acetate II(metastable) convert to less soluble form
cortisone acetate V ((stable) resulting caking of solid.
 This change can be preventing by dehydrating the molecular environment or
by adding viscosity building agent like PVP, CMC, pectin, gelatin.
 40 % drugs are polymorphic but barburates show highest 70% and sulphonamides
65 % in polymorphic form
 Amorphous form of drug which has no internal crystal structure represents
higher energy state and greater aqueous solubility than crystalline forms.

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Crystal forms ….
 Thus, the order for dissolution of different solid forms of drug is – amorphous >
metastable > stable
Hydrates/Solvates
 The stoichiometric type of adducts where the solvent molecules are
incorporated in the crystal lattice of the solid are called as the solvates & trapped
solvent is known as solvent of crystallization.
 Solvates can exist in different crystalline from is known as
pseudopolymorphism.
 When the solvent in association with the drug is water, the solvate is known as
hydrate.

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Crystal forms ….
 The organic solvates have greater aqueous solubility than the nonsolvates
 E.g. – Chloroform solvates of Griseofulvin is more water soluble than their
nonsolvated forms.
 Generally anhydrous form are more water soluble than hydrates because
hydrates are already in interaction with water & therefore have less energy for
crystal break up.
 Eg. Anhydrous Theophylline and ampicillin are more soluble than
Theophylline monohydrate and ampicillin trihydrate respectively.
Anhydrous >organic solvates>Non-solvates

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