This document discusses mixing and homogenization processes. It defines mixing as combining two or more substances together, and identifies perfect mixing as each particle of one material lying adjacent to a particle of the other material. The objectives of mixing are outlined. There are three types of mixtures discussed: positive, negative, and neutral. The mechanisms and equipment used for mixing powders, liquids, and semi-solids are described. Homogenization is defined as preparing a fine emulsion from a coarse one by converting large globules to small globules. Common homogenization equipment like hand homogenizers, Silverson mixers, and colloidal mills are summarized.

1. Mrs. Ashwini P. Shewale
principal
(PDEA’S College of
Pharmacy,Hadapsar, Pune
Mixing and Homogenization

2. Mixing and Homogenization
Mixing is the most widely used operation
in which two or more than two substances are combined
together.
Perfect mixing is that in which each particle of one material
lies as nearly adjacent as possible to a particle of the
other material.
The main objectives of mixing may be:
1 . Simple physical mixing of materials to form a uniform
mixture.
2. To promote the chemical reaction to get uniform
products.
3. Dispersion of solid in liquid to form suspension or paste.
4. Dispersion of two immiscible liquids to form an
emulsion.

3. TYPES OF MIXTURES
There are three types of mixtures —
1.Positive mixtures,
2. Negative mixtures
3. Neutral mixtures.
Positive mixtures:- When two or more than two miscible liquids
are mixed or soluble solid is dissolved in water, mixtures are
called positive mixtures. These mixtures do not present any
problem in mixing. Moreover the mixture formed is irreversible.
Negative mixtures :-When two immiscible liquids are mixed
insoluble solids are mixed with water it forms negative mixture.
For preparing such types of mixtures a higher degree of mixing
of materials is required. The mixture formed is a reversible
mixture.
Neutral mixtures:- These mixtures are static in their behaviour.
The substances do not have the tendency to mix with each other
immediately, but once mixed they do not separate after mixing.

4. Mixing mechanisms
The solid mixing takes place by a combination of one or
more mechanisms given below:
1. Convective mixing : There is bulk movement of groups
of particles from one part of powder bed to another. It
occurs by an inversion of the powder bed by means of
blades or paddles.
2. Shear mixing : When shear forces occur it reduces the
scale of segregation by thinning of dissimilar layers of a
solid material.
3. Diffusion mixing : It occurs when random motion of
particles within a powder bed causes them to change
position relative to one another. It is produced by any form
of agitation of powder.

5. There are various physical properties which affect the perfect mixing
of powders. These are discussed here under: .
1. Particle size : It is easy to mix two powders having approximate the
same particle sizes. The variation of particle size can lead to separation
also, because the small particles move downward through the spaces
between the bigger particles.
2. Particle shape : The ideal particle is spherical in shape for the purpose
of uniform mixing. The irregular shapes can become interlocked and there
are less chances of separation of particles once these are mixed together.
3. Particle attraction : Some particles exert attractive forces due to
electrostatic charges on them. This can lead to separation.
4. Material density : It is difficult to mix two powders having different
density. This is due to the fact that dense material always moves
downward and settles down at the bottom. Therefore, for uniform mixing
of powders, proper attention should be given to their density.
5. Proportions of materials : The best results can be achieved if two
powders are mixed in equal proportions by weight or by volume. In case
there is a large difference in the proportion of two powders to be mixed
the mixing of powders is always done in the ascending order of their
weights.

6. Equipment Used for Mixing of Powders
In the laboratory, the mixing is done by using pestle and
mortar or with the help of a drug spatula. The method is
commonly known as 'trituration'.
On large scale, the following equipment are used for
mixing of powders:
1.. Tumbler mixer 2. Double cone mixer
3. Agitated powder mixer 4. Air mixer
Equipment Used for Mixing of liquids:
1. Propeller mixer
2. Turbine mixer
3. Paddle mixer
Equipment are used for mixing of semi-solids:
1. Triple roller mill
2. Agitator mixer
3. Planetary mixer

7. Tumbler mixer
It consists of a metallic vessel in which powders are mixed
by slow rotation, either manually or with the help of an
electric motor. Due to rotation the ingredients come over
one another,
For mixing of large bulk of powders, the mixing of powders is
done in a vessel of a suitable design along with baffles
which gives a thorough mixing. The tumbler mixers are
generally made up of stainless steel and are of various
designs, such as cubical, V shaped, Y shaped and
cylindrical etc. These are rotated at a slow speed by using
an electric motor of suitable horse power. The rotation of
the vessel should be slow so that the powder does not
remain stationary against the side of the vessel held by
centrifugal force but lifted by baffles and fall over
continuously.

10. Double cone blender
It is developed in an attempt to overcome some of the
shortcomings of rotating mixers. The mixing of powder in
double cone blender is due to tumbling and shearing action
with blade, Double cone blender is made of stainless steel
and is available in different capacity ranging from 5 Kg to
200 Kg or even more. The of rotation. The rate of rotation
should be optimum which depends on the size and shape of
tumbler as well as nature of material to be mixed. The
common range is 30-100 r.p.m. The material to be blended is
loaded approximately 50 to 60% of the total capacity of the
blender. As the blender rotates the material undergoes
tumbling motion and mixes the material thoroughly. Agitate
blade can also be fixed in order to produce shearing action.
The double cone blender is an efficient design for mixing
powders different densities and is used mainly for small
quantity of powders.

14.  Agitated powder mixer It consists of a stationary vessel
or a trough in which an arm rotates and transmits shearing
action to the particles. The" end-to-end movement is
required for general mining which can be achieved by
fitting helical blades to the agitator, the
 mixer is commonly used for mixing free flowing powdered
materials having uniform particle size and
density.

15. Air mixer
The air movement can be used for mixing of powders. The
powders to be mixed are taken in a vertical cylindrical
vessel and air is admitted at its base at an angle after short
interval blasts. This gives a spiral movement to the powder.
The air should be admitted at short intervals and not
continuously. A typical method is to use eight air blasts of
two seconds duration with one second interval. Thus 24
seconds are required for proper mixing.

16. MIXING OF LIQUIDS
Mixing of liquids is done to prepare true solution or
emulsions.
Mixing is required to dissolve one miscible liquid into another
miscible liquid to form true solution. For making emulsion,
the mixing of two
immiscible liquids are done by using shear force.
Equipment Used for Mixing of Liquids
In the laboratory the emulsion is prepared by using pestle
and mortar and afterward it is passed through a
homogeniser to get fine emulsion. On large scale, the
following equipment are used for mixing the liquids:
1. Propeller mixer
2. Turbine mixer
3. Paddle mixer

17. Mechanism of Mixing for Liquid :
1. Bulk Mixing 2. Turbulent Mixing 3. Laminar Mixing
4. Molecular diffusion.
1) Bulk Mixing: The movement of relatively large portion of
material being mixed from one location to another
location in the system. This is mainly accomplished by
paddles revolving blades or other devices which moves
volume of fluid in different direction.
2) Turbulent Mixing : The phenomenon of turbulent Mixing
is a turbulence flow a fluid which can be characterized by
random fluctuation of fluid velocity at any point within the
system. In the turbulent flow are eddies of various sizes
are developed. [Eddies : An eddy is define as a portion of
fluid moving as a unit in the direction i.e. opposite to that
of the general flow of fluid].It is very effective mixing
mechanism.

18. 3. Laminar Mixing :
Stream line or laminar mixing means a flow is frequently
encountered when highly viscous liquid being process.
When two liquids are mixied through laminar flow the
interface between the liquid get streched and thinned.
4. Molecular diffusion :
The molecular diffusion result from thermal motion of
molecules, when it occurs in conjuction (in combination)
with laminar flow, this molecular diffusion tends to
reduced sharp discontinuities at the interfaces between
the fluid layers and result in complete mixing.

19.  Propeller mixer
It consists of a vessel and a propeller. The propeller usually
operates at high speed which is upto 8000 r.p.m. which
gives a satisfactory flow pattern to the liquids. During
mixing of liquids, air gets entrapped in liquids or there is
formation of vortex. This can be avoided by making the
following changes in the position of the propeller shaft.
 The propeller mixers are not suitable when considerable
shear force is needed e.g. in the preparation of emulsion.

22. Turbine mixer
It consists of a vessel and a circular disc impeller. A number
of short, straight or curved blades are attached to it. The
turbine impeller is usually rotated at somewhat lower
speed than the propeller. The turbine mixer is used for
mixing of more viscous liquids e.g. syrups, liquid paraffin,
glycerine etc.

23. Paddle mixer
In a paddle mixer, the flat blades are attached to vertical
shaft which rotates at a low speed of 100 r.p.m. For mixing
to low viscosity liquids simple flat paddles are used. But
for mixing of viscosity liquids, the big paddles, often
shaped to fit closely to the surface of the vessel, are used.
The paddles of different sizes and shapes are used in the
pharmaceutical industry according to the character of
viscosity of the product.

24. MIXING OF SEMI-SOLIDS
The mixing of semi-solids is done for preparing
ointments, creams,pill masses and wet mass for making
granules etc.
Equipment Used for Mixing of Semi-solids In case the
quantity is large, the following equipment are used for
mixing of semi-solids:
1. Triple roller mill
2. Agitator mixer
3. Planetary mixer

25. TRIPLE ROLLER MILL
Construction The mill consists of three rollers which are made of
a hard abrasion-resistant material. These rollers are arranged in
such a way that they come very close to each other. These
rollers are rotated at different rates of speed. The material
coming between the rollers is crushed depending on the gap
between them and the difference in rates of movement of the
two surfaces.
Working As shown in Fig. 7-5, the material after passing through
hopper, comes between roller 1 and 2 and is reduced in size in
the process. The gap between roller 2 and 3 is usually less than
that between 1 and 2, further crushes and smoothes the
mixture which adheres to roller 2. A scraper is arranged in such
a way, that it can remove the mixed material from the roller no.
3 and does not allow the material which has not passed
between both sets of the rollers to reach the scraper.
Uses The triple roller mill is very useful for the purpose of mixing
of solid powder in ointment base.

27. AGITATOR MIXER
The semisolid mixing can be carried out in the agitator mixers
meant for mixing liquids and powders. However, the mixers for
semisolids are usually of heavier Construction. Sigma arm mixer
is the commonly used agitator mixer for the purpose of mixing of
semisolids. The mixer has two blades, the shape of which
resembles the Greek letter "Sigma". The two blades move at
different speeds and towards each other. The blades operate in a
mixing vessel which has a double trough shape, each blade fitted
into a trough. The two blades rotate at different speeds, one
usually about twice the speed of the other which causes the
lateral pulling of the material and is divided into two troughs. The
difference in speed and shape of blades causes end-to-end
movement. Air is usually entrapped during the mixing of
semisolids. This can be avoided by enclosing the sigma arm
mixer and perating it under pressure. The sigma arm mixer is
commonly used for mixing of dough ingredients in the baking
industry. It is used in wet granulation process in the manufacture
of tablets. It is also used for mixing powdered drug with an
ointment base.

28. PLANETARY MIXER
Principle In a planetary mixer, the blade tears the mass
apart and shear is applied between a moving blade and a
stationary wall. The mixing arm moves around its own axis
and also around the central axis in order to reach every
spot of the vessel. The plates in the blade are sloped, so
that the powder makes an upward movement to produce
tumbling motion.
Construction It consists of a stationary vessel which is
made up of stainless steel. The vessel can be removed
either by lowering it beneath the blade or raising blade
above the vessel. The mixing blade mounted from the top
of the vessel. The mixing shaft is driven planetary gear
connected to an electric motor.

30.  Working The blade is moved slowly at the initial stage for
premixing of the material and finally at increased speed for
active mixing.
 In this way high shear can be applied for thorough mixing.
The blade and the stationary vessel provide a kneading action
and shear. This is due to narrow clearance between the blade
and the wall of the vessel.
 Uses The planetary mixer is used for its kneading action
required in wet granulation. It is also used for mixing of
powdered drug with an ointment base.

31. HOMOGENISATION
Homogenization is the process of preparing fine emulsion
from a coarse emulsion by converting the large globules to
small globules.Homogenisation is done in an apparatus
called 'Homogeniser'.
Principle The homogenizers are based on the principle that
the large globules in a coarse emulsion are broken into
smaller globules by passing them under pressure through
a narrow orifice.
The commonly used homogenisers are:
1. Hand homogeniser
2. Silverson mixer homogeniser
3. Colloidal mill

32. Hand Homogeniser.
Principle : It based on the principle that the large globules in a coarse
emulsion are broken into small globules by passing them under pressure
through narrow orifice.
Construction :
1. It consist of a hopper, small orifice, handle and a heavy Base.
2.' Hand Homogeniser consist of a small stainless steel vessel mounted on a
stand.
3. Bottom of the vessel has opening to fit nozzle.
4. A freely moving piston is operation in the cylinder.
Working :
1. The emulsion prepared in mortar and pestle is placed in the hopper of
emulsifier.
2. The piston is operated. The liquid to be homogenized is passed through
the nozzle under pressure which causes atomization and hence
homogenisation can be done.

34. Silverson Homogeniser
Principle : It works on the principle of combination of
mixing and homogenisation.
Construction :
1. It consist of Emulsifying head.
2. To which number of blades are attached.
3. It is surrounded by a fine mesh sieve made up of
stainless steel.
4. The head is rotated by means of small motar which
rotates the blades at very high speed.

35. 1. The emulsifying head is immersed in the liquid to be
emulsified.
2. The liquid to be mixed are sucked through the fine mesh and
oil is reduced into fine globule in this process.
3. The process of mixing occurs the high speed rotation of
blades.
4. The mixed materials is then pelled out with a great force and
thus the process of and homogenisation occurs
Simultaneously.
Application :
The mixer is used to obtain fine emulsion an suspension
and other biphasic liquid preparation.

38. Colloidal Mill :
Principle : works on the principle of shearing. The size reduction
is affected due to shearing.
Construction :
1. Colloidal Mill consist of rotar and stator.
2. The milling surfaces are conical and the gap between rotor and
stator ranges from 0.002 to 0.003 inches,
3. The rotor revolves at speeds of about 3000 to 20000rpm.
4. The material to be size reduced is pre milled.
5. Feeding the material through a hopper into the mill.
Working: |
1. The material and suspension is placed into the hopper of the
mill,
2. The material is thrown outwards, due to the centrifugal action of
rotor.

39. 3.Particle size reduction is effected when the material is
passes between the milling surfaces.
4.The product obtained from mill has a very fine particle size.
Application :
Colloidal Mill are frequently used for the preparation of
pharmaceutical suspension and emulsions, with a particle
size of less than a micron.

40. Colloidal Mill

41. VISCOSITY
Every liquid has itsown flow rate. Liquids like water, alcohol,chloroform and
acetone move fast, whereas syrup, honey and glycerine flow slowly This
rate of flow of liquid depends on the internal resistance involved when one
layer moves over another layer. In other words, the property of a liquid
which gives its resistance to flow is called viscosity.
Liquids of high viscosity do not flow readily due to their high internal fractional
resistance. The more the resistance to flow the more will be the viscosity of
the liquid.
Viscosity of liquid decreases with rise in temperature, while it increases with
fall in temperature.
In C.G.S. system the viscosity of a liquid is measured in dyne-second per
square centimeter. It is also known as "Poise". Each poise is further
divided into 100 centipoise.
In S.I. system, the viscosity is measured in Newton-second per square
metre. The viscosity of water is one centipoise. The viscosities of liquids
are normally expressed as relative to water.

42. The viscosity of the liquid is measured by comparison with a
liquid of known viscosity. There are a number of instruments
which are used asurement of viscosity of liquids. Some of
these are:
1. Ostwald viscometer 2. Falling sphere viscometer
3. Redwood viscometer 4. Cone and plate viscometer
OSTWALD VISCOMETER
Construction It consists of "U" tube having two bulbs X and Y.
A capillary tube CD of a suitable bore is fitted to one arm of
U tube. The viscometer is placed vertically in a
thermostatically controlled bath.
 Working A liquid whose viscosity is to be determined is
placed in arm Y to fill the tube to mark E. It is then sucked or
blown up to a point 1 cm above A. The time (t) for the liquid
to fall from mark A to mark B is measured.
 The density of liquid (d) is determined.

43. The whole procedure is repeated with a liquid of known
viscosity and time (t2) is noted for the fall of liquid from
mark A to B.

44. Applications of viscosity in pharmacy
1. Viscosity plays an important role in the stability of
emulsion and suspensions..
2. Ophthalmic preparations are made viscous to prolong
the-contact time of the drugs e.g. methyl cellulose is used
for this purpose.
3. Paints are made more viscous so that they may remain in
contact with skin for long time e.g. glycerine is included in
paint formulation to increase the viscosity.
4. Fats, waxes and other viscous substances are filtered at
higher temperature. It is due to the fact that at higher
temperature, there is decrease in viscosity and hence rate
of filtration can be increased,

45. 5. Certain pharmaceutical formulations are standardized on
the
basis of its viscosity e.g. liquid extract of liquorice.
6. The viscosity of certain liquid preparations is increased in
order
to improve pourabiiity or to make the preparation more
palatable.
SURFACE TENSION
 The molecules of the interior of a liquid attract one another
equally in alt directions. At the surface of the liquid, the
attraction is only in downward and sideward direction and
this causes the surface layer to exist in a state of tension,
which is called surface tension. Due to this

51. Mixer blade
Planetary gear
Direction of drive
Direction of rotation
of planetary gear
Stationary
ring gear
Top view

58. 58