This document discusses mixing and homogenization in pharmaceutical manufacturing. It defines mixing as treating components in an unmixed or partially mixed state so that each particle is in contact with others. Mixing is used to make simple mixtures, promote reactions, and ensure uniformity. It describes positive, negative, and neutral mixtures. It also discusses different types of mixing like convection, diffusive, and shear mixing. Finally, it summarizes various equipments used for liquid, powder, semi-solid, and homogenization mixing in pharmaceutical production.

1. PRESENTED BY :
Ms. Harshada Bafna.
M. Pharmacy (QA)
Mixing and Homogenization

2.  Mixing may be defined as a unit operation in which two or more
components, in an unmixed or partially mixed state, are treated so
that each particle, molecule etc. of the components lies as nearly as
possible in contact with a unit of each of the other components.
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3.  To make simple physical mixture
 Physical change
 Dispersion
 Promotion of reaction
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4.  To ensure uniformity
 To initiate or to enhance the physical or chemical reactions
e.g. diffusion, dissolution etc.
 To make the following products:
o Tablets
o Suspensions
o Emulsions
o Pastes
o Creams
o Ointments
o Solutions
o Syrups
o Tablet coatings
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5. When two or more
than two miscible
liquids are mixed or
soluble solid is
dissolved in water,
the mixture are
called positive
mixture.
 In this case no
energy is required
and no problem is
formed.
when two immiscible
liquids are mixed or
insoluble solids are
mixed with water it
forms a negative
mixture.
A higher degree of
mixing energy is
required and these
mixtures are very
difficult to prepare.
The substances do not
have the tendency to
mix with each other
immediately, but once
mixed, they do not
separate out easily.
They are static in
behavior.
Examples-Pastes,
ointments etc.
Positive
Mixture
Negative
Mixture
Neutral
Mixture
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6. o Transfer of groups
of particles in bulk
take place from one
part of powder bed
to another.
o It occurs when
random motion of
particles within a
powder bed causes
them to change
position relative to
one another.
o Shear forces are
created within the
mass of the
materials by using
agitator.
Convection
Mixing
Diffusive
mixing Shear
mixing
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7. High density
Greater difficulty in mixing, because
heavier material moves downward
through the lighter materials.
Different particle size
Difficulty in mixing because the smaller
particles can move downward through
the spaces between the larger particles.
Spherical shape of particles/
Irregular shape of particles
Ideal for mixing.
Small particles
Greater electrostatic charge
Aggregation of particles.
Equal amount of materials
Easy to mix.
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8.  Run at 8000rpm.
 Provides longitudinal movement of
liquid.
 It is used for low viscosity liquids.
 Disadvantage: little shear is not
suitable for emulsification.
 4, 6 or 8 blades…(axial turbine or
radial turbine).
 Diameter is 30-50%of vessel.
 Rotates at lower speed 50-
200rpm.
 More shear force suitable for
viscous liquids.
Propeller mixer Turbine mixer
Equipments for liquid Mixing
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9.  2 or 4 blade paddles are common.
 They have large surface area.
 Rotate at 100rpm.
 Useful for viscous and semisolid
preparations.
Paddles mixer
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10. Equipments for powder Mixing
On the large scale , the following equipment are used-
1. Tumbler mixer -
 It consist of a metallic vessel in which powders are mixed
by slow rotation, either manually or with the help of an
electric motor.
 These are generally made up off stainless steel and are
various designs, such as cubical V shaped shaped and
cylindrical etc.
 The rotation of the vessel should be slow so that the
powder dose not remain stationary against the side of the
vessel held by centrifugal force but lifted by baffles and fall
over continuously.
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11. 2. Double cone blender-
Developed to overcome the shortcoming of rotating mixer.
Mixing of powder is done by tumbling and shearing action with
blade.
Made up off stainless steel and available in different capacity
ranging from 5kg to 200kg or more.
The efficiency of the blender mainly depends on the speed of
rotation.
Rate of rotation should be optimum which depends on the size
and shape of tumbler as well as nature of material to be mixed.
30-100r.p.m.
Uses-
1. used for mixing powders of different densities.
2. used mainly for small quantity of powders.
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12. 3. Agitated powder mixer-
 It consist of stationary vessel or a trough in which an arm
rotates and transmits shearing action to the particle.
Uses-
1. Used for mixing free flowing powdered materials having
uniform particle size and density.
4. 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.
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13.  The mixing of semi-solid is done for preparing ointments ,
creams, pill masses and wet mass for making granules.
 Apparatus used:
• Planetary mixers
• Agitator mixers used as sigma blade mixers.
• Triple roller mills.
Equipments for semi-solid Mixing
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14.  Principle –
In a planetary mixer, the blade tears the mass apart and
shear is applied between a moving blade and 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 a 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 the blade above the vessel. The
mixing blade is mounted from the top of the vessel. The mixing
shaft is driven by planetary gear connected to an electric motor.
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16.  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 wall of the
vessel.
 uses-
1) It is used for its kneading action required in wet
granulation.
2) It is also used for mixing of powdered drug with an ointment
base.
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17.  It is an example of agitator mixers.
 Its shape resemble the Greek letter sigma.
 It uses 2 mixer blades.
 The two blades rotate towards each other and operate in a
mixing vessel which has a double trough shape, each blade
fitting into a trough.
 The two blades rotate at different speeds, one usually about
twice the speed of the other, resulting in a lateral pulling of
the material and divisions into two troughs, while the blade
shape and difference in speed causes end-to-end movement
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18.  uses-
1) It is commonly used for mixing of dough ingredients in the
baking industry.
2) Used in wet granulation process in the manufacture of
tablets.
3) It is also used for mixing powdered drug with an ointment
base.
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19. construction
o It is fitted with three rollers, made up of hard abrasion- resistant
materials.
o Rollers are fitted in such a way that they come in close contact with
each other and rotate at different speeds.
o A scraper is used to remove the final ointment of smooth and uniform
texture.
o The feed enters through a hopper.
working
o The material passes through hopper A, in between rollers B and C
where size reduction occurs.
o Then the ointment is passed between the rollers C and D, where it is
further reduced in size and a smooth mixture is obtained.
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20. Uses-
It is very useful for the purpose of mixing of solid powder
in ointment base.
oThe gap between rollers C and D is usually less than the gap
between B and C
oThe smoothened material is continuously removed from roller
D by means of scraper E, from where it is collected in a
receiver.
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21. Definition - It is process of preparing fine emulsion from a
coarse emulsion by converting the large globules to small
globules.
It is done in an apparatus called Homogeniser.
Principle – the homogenisers are based on the principle that
the large globules in a coarse emulsion are broken into
smaller globules by passing them under pressure a narrow
orifice.
The commonly used homogenisers are-
1. Hand homogeniser.
2. Sliver son mixer homogeniser
3. Colloidal mill.
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22.  Most commonly used hand homogenizer on laboratory.
 Consists of a hopper, small orifice, handle and a heavy base.
Process:
 The preformed emulsion is placed in the
hopper of the emulsifier
 The emulsion is then forced to pass
through a narrow orifice by up and
downward movement of the handle which
reduces the size of the oil globules
 This reduction in size increases with the
speed of pumping.
Hand homogeniser
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23.  Consist of an emulsifying head to which
blades are attached, surrounded by a fine
mesh sieve made up of stainless steel.
 The emulsifying head is emerged into
liquids to be emulsified.
 The head is rotated by means of a small
motor which rotate the blades at high
speed.
 Mixing capacity 9 liters to 9000 liters.
Silver son Mixer- homogeniser
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24.  Principle –
The size reduction is affected due to shearing, when the
material is passed between the narrow gap of milling surface of
rotor and stator.
 Construction –
It consists of a rotor and stator. The rotor rotates at speed
of 3,000 to 20,000 r.p.m. the stator have conical milling surface
between there is an adjustable clearance between 0.002 to 0.003.
Colloid Mills
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25. Working –
the material e.g. emulsion and suspension is
placed into the hopper of the mill. It is then
passed through the narrow gap between the rotor
and stator and thus reduced the fine particle size.
Uses-
 Use for producing the particles in micron
size.
 Used to prepare the pharmaceutical
suspension and emulsion having particle size
less than one micron.
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26. Viscosity
Viscosity is a property of liquids that is closely related to the
resistance to flow.
Liquids of high viscosity do not flow readily due to their high
internal fraction resistance.
Viscosity of liquids decreases with rise in temperature , while
increases with fall in temperature.
Measurement of viscosity –
The viscosity is measured in both C.G.S. and S.I. system.
1. C.G.S.-
 Measured in dyne second per square centimeter/ poise.
2. S.I. –
 Measured in Newton second per square meter.
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27.  The viscosity of water is one centipoise.
 Instrument used for measurement of viscosity –
1. Ostwald viscometer.
2. Falling sphere viscometer.
3. Redwood viscometer.
4. Cone and plate viscometer.
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28. Construction -
The apparatus consists of a glass U-tube
viscometer made of clear borosilicate glass
and constructed in accordance with the
dimensions given in official books.
Ostwald viscometer.
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29. Working -
• Fill the viscometer with the liquid being examined through tube L
to slightly above the mark G, using a long pipette to minimize
wetting the tube above the mark.
• Place the tube vertically in a water bath and when it has attained
the specified temperature, adjust the volume of the liquid so that
the bottom of the meniscus settles at the mark G.
• Adjust the liquid to a point about 5 mm above the mark E.
• After releasing pressure or suction, measure the time taken for the
bottom of the meniscus to fall from the top edge of mark E to the
top edge of mark F.
• The viscosity of the unknown liquid can be determine by –
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30.  Stability of emulsion and suspension.
 Ophthalmic preparation.
 Paints.
 Fat , waxes and other viscous substances are filtered at higher
temperature. Due to that at higher temperature, there is
decreases in viscosity.
 Improve pourablity.
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