MIXING AND FILTRATION FOR S.Y pHARMACEUTICS

1. Mixing & Filtration
By :
Varsha Patil and Rupali Bhoje
1

2.  Mixing may be defined as an operation in which,
each particle of any one ingredient, lies as close
as possible to the adjacent particles of the other
ingredient.
OR
 Mixing is defined as a process that tends to result
in a randomization of dissimilar particles within a
system.
APPLICATIONS:
 -Uniformity , composition and dose accuracy.
 -Enhances the rate of chemical reaction, rate
of dissolution

3.  Mixing of liquids
Mixing occurs in two stages:
• Localized mixing which applies sufficient
shear to the particles of the fluid
• A general movement sufficient to take all
parts of the material through the shearing
zone and to ensure a uniform final
product.
3

4. TYPES OF MIXING
-1)According to physical stability of mixture:-
a) Reversible mixing
b) Irreversible mixing
c) Neutral mixing
-2)According to state of matter:-
a) Solid-solid mixing
b) Solid-liquid mixing
c) liquid-liquid mixing

5. LIQUID MIXING
 One or more solids or liquids are mixed with
another liquid to produce pharmaceutical liquids.
Depending upon solubility of solutes, the liquid
mixing is of 2 types:
 1) liquid-liquid mixing:
-soluble/miscible phases to produce monophasic
liquids.
-immiscible liquid phases to produce emulsions.
 2) solid-liquid mixing:
-soluble solid to produce monophasic liquids.
- insoluble solids to produce suspensions.

6. MONOPHASIC LIQUIDS
 Monophasic liquids are prepared by mixing solids
or miscible liquids with another liquid usually
water, to produce a singe phase homogenous
mixture.
 Such mixing occurs by diffusion, and it is termed
as blending. It does not require a high level of
shear.
 Simple shaking or stirring is enough for lab scale
and on large scale, propeller mixers are preferred.

7. MECHANISM OF LIQUID-
LIQUID MIXING
 1) Laminar mixing: During mixing, the fluid
immediately adjacent to the agitator moves in streamlines
parallel to the direction of flow. The viscous drag then
causes mixing of entire content by stretching, cutting and
folding.
 Ex- mixing of viscous liquids by impellers
 2) Turbulent mixing: The paddles and turbines exert
pressure on the liquid adjacent to them. The fluid moves not
only in parallel paths but also in erratic and random paths.
The decrease in pressure behind the blades circulates fluid
from the surrounding area to the agitator. The turbulent
eddies produced around the blades transfers the mass from
one layer to another. It is highly effective mixing.

8.  3) Molecular Diffusion: It involves movement of
molecules from layer of higher concentration to
lower concentration till equilibrium is
maintained.
 4) Bulk Transport: The mixing of liquid by
convection or bulk transport involves movement
of large portion of material from one location to
another. This is observed when 2or more paddles
are assembled in a vessel to move adjacent
volumes of the fluid in different directions.

9. FLOW PATTERNS
 Impeller agitators produce fluid velocity in the
following types of flow patterns:
 A) Tangential: In this pattern the liquid moves
parallel to the direction of the impeller.
 B) Radial: In this the liquid is discharged outwards
from the impeller in a direction perpendicular to
the impeller shaft.
 C) Axial: In this the liquid is discharged
downwards to the bottom of the vessel and the flow
lines spread along the floor of the vessel, sweeping
the elements off the bottom and directing them
upwards. Therefore this flow is desirable for
preparation of biphasic liquids.

10. Axial & Radial Flow
Axial Flow Radial Flow
10

11.  Impellers-An impeller is a part of a pump or compressor that
rotates at a high speed and acts as a propeller to increase a fluid's
pressure and flow rate.
 2 types
 1. Generate currents parallel with the axis of
impeller shaft Axial-flow impeller
 2. Generate currents in a radial or tangential
direction Radial flow impellers
 Axial flow impellers impose basically bulk
motion, and are used in homogenous liquids.
 Radial flow impellers impose shear
stress to the fluid, and are used to mix immiscible
liquids 11

12. 12

13.  High Efficiency Impellers
 High efficiency impellers are designed to produce
 more uniform axial flow and better mixing
 It Reduces power requirements
 In high efficiency impellers, blades are sometimes
folded to decrease the blade angle near tip
 It is used to mix low to moderate viscosity liquids but
not for very viscous liquids or dispersing gases.
13

14.  Impellers for highly viscous liquids
 Helical ribbon impeller
 Having diameter almost equal to inside diameter of
 tank
 Promotes liquid motion all the way to the tank
 wall with very viscous liquids
 Anchor Impeller
 Creates no vertical motion
 Less effective than helical
 Promotes better heat transfer
 May have scrapers to remove liquid from tank
wall
14

15. Types of Mixers
 Propeller mixer- A propeller is a type of fan that
transmits power by converting rotational motion into thrust.
The three-blade marine type propeller is most suitable
for low energy mixing such as mixing of soluble
substance.
Suitable for mixing low viscosity fluids rotated at
1750-2000 rpm.
Fluids with high viscosity(200cps) rotate at lower
speed of 400-450 rpm.
Major problems are-
• Vortex formation
• Air entrapment
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16. 16
Vortex formation and its disadvantages
If solid particles are present, they will be
thrown at the outside by centrifugal force;
and move downward and to the centre of
the tank at bottom
Instead of mixing; (reverse) concentration
occurs
Relative velocity b/w blades and liquid is
reduced
Hence power that can be absorbed by the
liquid is limited

17.  REASON-Due to the high speed of the propellers vortexing
and finally aeration may occur; i.e. air may get entrapped
which may be difficult to remove from the product and the air
may encourage oxidation in some cases.
 To avoid vortexing the following strategies can be worked
out:
 (i) The propeller should be deep into the liquid and
 (ii) Symmetry should be avoided:
 (a) propeller shaft may be off-set from the center.
 (b) propeller shaft may be mounted at an angle to the vertical
wall of the container.
 (c) the shaft may enter side of the vessel
 (d) or, a vessel other than cylindrical may be used,
 (N.B. although this is liable to give rise to ‘dead spots’ in
corners)
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18. 18
(iii) A push-pull type of propeller may be used
in which two propellers of opposite pitch are
mounted on the same shaft so that the rotating
effects are in opposite directions and cancel
each other.
(iv) One or more baffles may be used which are
usually vertical strips attached to the wall of the
vessel.
Use:
(i) Propellers are suitable when strong vertical
currents are required e.g. in suspensions of
solids in liquids.
(ii) They are not suitable when considerable
shear is required, as in emulsification.

19. Propeller positions
At angle
Push-
pull
At centre Variable
19

20. Types of Mixers
 Turbine mixer
Impellers with short blades that may be flat,
curved or pitched.
They usually rotate at slow speed of up to 300 rpm
& are suitable for liquids having viscosity up to
100000 cps.
The flat blade turbines produce high shear force &
radial flow. They are more suitable for mixing &
milling of immiscible liquids.
The pitched blades produce axial flow & need less
power. More suitable for suspension mixing.
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21.  Disk Turbine- like straight blade turbine
creates zones of high shear rate
ex- Dispersing a gas in a liquid
 Pitched blade- turbine is used when
good overall circulation is important
21

22.  Straight blade force liquid radially and
tangentially with no vertical movement.
 Current moves outward to vessel wall and then either
upward or downward
 Also called paddles
22

23. Types of Mixers
 Paddle mixer
Impellers with one or more horizontal blades.
They rotate at slow speed of 50 - 100 rpm.
They produce tangential or radial flow with low
shear force.
They are more suitable for mixing of highly
viscous liquids & sticky materials.
Less air entrapment & no generation of heat.
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24. Turbine & Paddle mixers
Pitched blade impeller
Paddle blades
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25. Liquid tank design
25

26. Definitions
 Filtration:
Process of separation of solids from liquids or
gases by means of a porous medium that
retains only the solids.
 Clarification:
It is the technique employed to achieve clarity
of a solution by separating any matter that
interferes with its transparency.
 Ultrafiltration:
Separation of colloidal particles below
1000m.
26

27. Some Common Terms
Slurry of solids in liquid is passed through
the porous filter medium.
The solids are retained in the form of filter
cake.
The liquid that passes through is called
filtrate.
The porosity of the filter cake can be
increased with help of filter aids.
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28. Filtration rate
 Given by Darcy’s Law
dV/dt = KA dP/ñL
 dV/dt: Rate of filtration
K: permeability constant of filter medium &
filter cake
dP: Pressure difference across the filter
medium & filter cake
L: thickness of filter cake
ñ: viscosity of the fluid
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29. Factors affecting filtration
 Permeability constant (K)
It is constant for a particular set of filtration. Clean
filter with open pores has higher permeability. As
the cake forms, the pores are blocked & higher
pressure is required to maintain the rate of filtration.
 Viscosity of fluid
Low viscosity is preferred. This can be achieved by
hot filtration if there are no thermo-labile or volatile
components. Dilution of liquid can be useful if the
total time required is reasonable.
 Morphology of filter cake
Hard & non – porous cake reduces the rate of
filtration.
The coarse particles of filter aid create channels in
the cake & prevent clogging. They may get blocked
by the fine particles & hence agglomeration of finer
particles before filtration is advisable. 29

30. Factors affecting filtration
 Area of filter bed
Direct relationship with effective available
area. Can be increased by using multiple
small units e.g. pleated filter paper or fluted
funnel. Constant removal of the cake also
helps to increase the area.
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31. Factors affecting filtration
 Pressure difference:
Application of positive pressure on the liquid or
vacuum beneath the filter increases the rate of
filtration. This can be achieved by-
• Gravity- Maintaining head of slurry above the filter
medium.
• Positive pressure- Application of positive pressure on
the liquid after initial low pressure.
• Vacuum – Also reduces the risk of explosion but
reduction in pressure also reduces the boiling point of
solvents & they may boil inside the receiver.
• Centrifugal force- for concentration & collection of
insoluble matter from in filterable slurry.
 Thickness of filter cake:
Formation of thick cake reduces the rate of filtration.
Constant removal of the cake or decantation helps
to increase the rate of filtration. 31

32. Components of filter
 Filter medium:
Porous surface that retains the solid particles
& supports the filter cake.
Ideal Properties:
• Mechanically strong.
• Remain porous & not get clogged or shrink
during the process.
• Physicochemical properties unaffected by the
liquid.
• Not absorb or retain the soluble ingredients.
• Easy to wash.
32

33. Types of Filter Media
Filter paper:
• Pore size of the paper can be selected on basis
of the size of particles to be removed-
Coarse 3.4-5.0
Medium 2.1-2.8
Fine 0.4-1.1
• Has some absorption capacity, tendency to shed
fibers & has less strength.
• High quality papers like Whatman papers have
good efficiency.
Cotton wool:
• Used as a wet plug for coarse filtration.
• Also has tendency to shed fibers. 33

34. Types of Filter Media
Filter cloth:
• Available in various porosity, strength & surface
area as weaving can be varied.
• Synthetic cloth has less absorption than cotton
cloth & so nylon cloth is used in large filer
press.
• Wear & tear increases processing cost.
• Fine muslin cloth is used for coarse filtration
(pre- filtration).
Glass wool:
• Used for filtration of corrosive liquids,
strong acids & alkalis and oxidizing
agents.
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35. Types of Filter Media
Asbestos :
• Granular particles of asbestos, sand &
kieselguhr are built on support material to
produce material of definite porosity.
• Used for filtration of corrosive liquids.
Membrane filters:
• Special polymers such as nylon, cellulose
acetate & cellulose nitrate are used.
• Can be used for sterilization of liquids
• High flow rates, mechanical strength, no
retention or contamination of the filtrate
• May not be suitable for organic solvents.
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36. Types of Filter Media
Sintered glass filters :
• Glass filter discs of various porosity are
prepared using glass granules of high
resistance.
• Useful alternative for filter paper in case of
reactivity problems.
• Also used for parenteral solutions.
• Need vacuum for faster filtration.
Selection of the medium depends
upon the type of liquid, its viscosity, quantity,
solid content, proportion of fine & coarse
particles & purpose of filtration.
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37. Filter Aids
 They are porous, rigid, irregular shaped
solid materials added to the filter cake to
improve the rate of filtration. They form a
porous cake of low resistance to flow.
 Ideal properties of filter aids:
Form & maintain a porous structure
Formation of thin layer
Effective at low concentration
Light & insoluble in the filtrate
Non- shedding, inert & free from impurities
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38. Filter Aids
Types of filter aids:
• Kieselguhr- Effective even at conc. of 0.1%
• Can increase filtration rate 5 times
• cellulose- Inert, pure but expensive. Caking
tendency.
• Asbestos- Good aid but sheds fibers. Soluble in
acids & alkalis.
• Diatomaceous earth (silica)- Inert, insoluble,
available in various pore sizes & range. Suitable
for fine filtration. Soluble in dilute acids &
alkalis.
• Perilte (Alu silicate)- Also available in various
pore sizes & range but forms a compressible
cake.
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39. How to Use Filter Aids
Two techniques:
• Pre-coat method:
A slurry of the filter aid is filtered
before the liquid to form a porous
cake at the surface of the medium.
• Dispersion method:
The aid is dispersed in the slurry.
39

40. Lab scale Filtration
The apparatus consists of the filter medium
(muslin, cotton or paper) & a frame or funnel
to hold the medium.
The medium has to be washed before
filtration to remove any loose fibers.
For the same reason, first few ml of filtrate
have to be discarded. This also helps in
rinsing.
After filtration, some amount of vehicle is
passed to rinse the filter & the same can be
used to make up the volume.
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41. Industrial Scale Filtration
Various types of filters are used depending
upon the requirement-
• Filter press
• Filter leaf
• Filter candles
• Meta filters
• Sintered filters
• Membrane filters
41

42. Filter press
 Construction:
It has three basic units-
• Grooved plate, frame & filter cloth.
The grooved plate has an outlet for the filtrate
& acts as support for the filter cloth.
The frame is open at both ends & is used as
inlet for the slurry.
The filter cloth is fitted on each side of the
plate & the frame & plate are placed
alternately. Each plate acts as a filtration unit.
The entire unit is placed in an outer jacket.
42

43. Filter press
 Construction:
Outlet of each unit is connected to a common outlet.
Usually the plate & frame are made from stainless
steel or silver plated steel.
Molded polyester or other plastic materials may be
used as they are lightweight or for inertness.
43

44. Filter Press
44

45. Filter press
 Working :
The slurry enters the chamber under pressure
between two plates & passes through the filter
cloth to the surface of the plate.
The filter cake is retained & the filtrate is
collected in the plates & passed out from the
common outlet. This process continues till the
frame is filled with filter cake.
The frame is emptied, washed & reassembled
before continuing the process.
Modified filter presses are available with
online washing arrangement.
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46. Filter press
 Advantages :
Simple construction, easy to assemble, clean &
maintain.
Provides large surface area for filtration.
Available in different capacity ranges.
The filter cake can be washed easily & effectively.
 Disadvantages :
Batch wise filtration.
Costly as labor cost in frequent cleaning &
assembling and wear & tear of filter pads is more.
Useful for slurries with <5% solids.
Washing is difficult if the cake is insufficient.
46

47. FILTER LEAF
 Construction-It consists of metal frame enclosing a
wire screen or a grooved plate. The screen is covered
by filter-cloth, which is fitted in a frame, to grip the
cloth. The frame may be square,rectangle,or circular
in shape and the outlet is connected to vacuum.
 Working- The filter leaf is placed in a vessel
containing slurry. When vacuum is applied, the
liquid flows inside the filter through the filter cloth,
leaving behind the cake on surface of cloth. The cake
can be simply washed by immersing it in a vessel
containing water or by reverse flow of air.
47

48. 48

49. FILTER CANDLES
 These are hollow cylinders of sintered porcelain or
kieselguhr,one end of which are closed. Hence called
filter candles. Open end is connected to a vacuum
pump. The candles are placed in a solution to be
filtered and negative pressure is created inside. The
deposited cake is removed by washing water,
scratching the surface with soft brush or by passing
water in reverse direction.
 DISADVANTAGE-of kieselguhr candles are les
robust, absorb more solution, and difficult to clean.
49

50. 50

51. META FILTERS
 Construction-also called as edge filter where edge of
filter media is the site of filtration. It is different from
other filters as it provides a surface of filter media
for filtration.Meta filter consists of stainless steel
rings with semicircular projections on one surface.
When these rings are packed together on rod, they
form a tapering channel. The central rod has grooves
on the surface, which provides a channel for
discharge of the filtrate.
 Working-It is mounted in the vessel containing
slurry. Under vacuum liquid flows outside to inside
and enters discharge channel formed by the central
rod. For fine filtration filter aids such as
kieselguhr can be used upon a pack of rings. 51

52.  Advantages-
 It can withstand high pressure, so used for filtration
of viscous liquids such as syrups.
 No problem of wear and tear.
 Cake removal is simple by reverse flow of water.
52

53. SINTERED FILTERS
 Are prepared from fine particles of ground glass or
ceramics, which are heated to sintering point so that
they form a disc. Sintered glass is made from finest
particles of high grade borosilicate glass.
 Advantages-No contamination of filters
 No absorption
 Easy to clean
 Can be used for filtration under pressure /vacuum.
 Filter with pore size below 2 mm used to remove
bacteria.
 Disadvantage- Porcelain filters are robust but get
blocked easily.
53

54. 54

55. MEMBRANE FILTERS
 These filters are made up of various membranes such as
cellulose acetate, cellulose nitrate,
polycarbonate,polysulfone and nylon.
 Available in various pore sizes-0.2-0.45mm used for
sterilization and 0.8-1.2mm used to filter air borne
particles.
 Widely used for high flow rate.
 No contamination of filtrate and retention of solution.
 Can be used with prefilters to remove larger particles.
 Disadvantages-Gets easily blocked
 Dissolution of membrane in organic solvents such as
ketone, esters.
55

56. REFERENCES
 Lachman Leon,Liberman Herbert
A, Kaing Joseph L., ‘’The Theory
and Practice of Industrial
Pharmacy, Varghese Publishing
House ,Mumbai.
 Atmaram Pawar, ‘ Introduction to
Pharmaceutics’, CAREER
Publications,Nashik. 56