Mixing

Sana Inam
Assistant Professor
Faculty of pharmaceutical sciences , GCUF
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 Mixing of solids
• In the manufacturing of tablets or granules normally a number of additives
are added. Therefore mixing of powder becomes essential part of the
process.
• Mixing is considered as a critical factor, especially in case of potent drugs
and low dose drugs where high amounts of adjuvants are added.
• The diverse characteristics of particles such as size, shape, volume, surface
area, density, porosity & flow charge contribute to the solid mixing.
• Depending on their flow properties solids are divided into two classes as
cohesive and non cohesive.
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Interparticle interactions & segregation
• forces that operate at particulate level are essentially of two types
• 1.Inertial forces:
• These forces hold neighboring particles in fixed relative position. E.g. Vander Waal
forces, electrostatic forces, surface forces.
• Surface forces: Cohesive forces and frictional forces results in surface-surface
interactions which resist the movement of particles, hence they should be minimal.
• During mixing, the particles develop surface charge which produce particle-particle
repulsions, which make random mixing impossible. These depend on surface area,
surface roughness, polarity & charge.

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Interparticle interactions & segregation
• Segregation:
Poor flow properties
Particle size difference
Differences in particle density and shape.
Transporting stage
Dusting stage
• It may occur even after mixing.
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Interparticle interactions & segregation
• 2. Gravitational forces
• Improve the movement of two adjacent particles or groups of particles
relative to each other
• When particle-particle collisions occur , exchange of momentum is achieved
• continuous exchange or distribution of momentum between translational
and rotational modes is necessary for effective mixing
• Efficiency of momentum transfer depends on
• Elasticity of the collisions Coefficient of friction Surface area of
contact Centrifugal forces
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 Mixing mechanism
• Solid mixing proceeds by a combination of one or more mechanisms
1-Convective mixing
• Analogous to bulk transport of liquids & is characterized by the
random motion of solid particles
• In it groups of particles are rapidly moved from one position to
another due to the action of a rotating agitator , paddles & blades

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 Mixing mechanism
2- shear mixing
• mixing is achieved due to the removal of force of attraction between
the particles.
• shear reduces the scale of segregation by thinning the dissimilar
layers
• Blenders with high speed chopper blades are examples of shear
blending.

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 Mixing mechanism
3-Diffusive mixing
• Mixing of individual particles is referred to as diffusive mixing
• occurs by random movement of particle within a powder bed and causes
them to change their relative position in relation to one another
• When a powder bed is forced to move, it will dilate (The volume occupied
by the bed will increase). This occurs because the powder particles become
less tightly packed and there is an increase in the air spaces or voids between
them. So there is the potential for the powder particles to pass through the
void spaces created under gravitational forces (in tumbling mixer) or by
forced movement (in fluidized bed).
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 Degree of mixing

Perfect mixing Random mixing Segregated mixing

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 Mixing techniques
1. Trituration : This is used both to reduce the particle size and mix
powder. A glass mortar-pastel may be preferred for chemicals.
2. Spatulation: Mixing of powder is done by movement of a spatula
throughout the powders on the sheet of paper.
3. Sifting: The powder is mixed by passing through sifters. This
processes result in a light fluffy product.

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 Mixing techniques
4. Geometric dilution:
• is used when potent substance are to be mixed with a large amount of diluents.
For example: 100 mg potent drug mixed in 900mg of lactose.
• According to geometric dilution: 100mg of potent drug + 100mg of lactose = 200mg
mixture
• 200mg of potent drug + 200mg of lactose = 400mg mixture
• 400mg of potent drug + 400mg of lactose = 800mg mixture
• 800mg of potent drug + remaining of lactose=1000 mg mixture.
5. Tumbling: In this the powder is mixed in a large container rotated by an electric motor

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Classification of equipment

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 1- Tumbling mixer
• movement of whole mixer is responsible for mixing action of solid.
• construction:
• usually consist of metallic vessels which are rotated on their horizontal axis
at optimum speed by means of motor
• The mixing vessel is usually made up of stainless steel and have door for
loading/unloading of material.
• The door is usually lined with rubber which provides a perfect seal after
closure.

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 1- Tumbling mixer
• Tumbling mixture are available in variety of shapes and sizes these
include;
1. Y-cone blender
2. Cubical blender
3. Double cone mixer
4. Twin shell / V-shaped mixer ( most popular)

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1- Tumbling mixer

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 1- Tumbling mixer
• Working:
• The material to be mixed is loaded into mixing vessel which is rotated at low speed
by electric motor
• Due to slow speed of rotation the powder is raised along the sides of the vessel until
the angle of repose is exceeded.
• The powder then tumbles down and mixing of compound occurs
• Efficiency of a tumbler mixer highly depends on the speed of rotation. It should be
critical and optimum (30-100 rpm)
• If the speed of rotation is too slow, it will cause sliding only so proper mixing will
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not occur
 1- Tumbling mixer
• If it is rotated at high speed ---the material will adhere to the walls due
to centrifugal force
• Mixing mostly occurs by convective mechanism
• Shear mixing will occur as a velocity gradient is produced, (the top
layer moving with high velocity and the velocity decreasing as the
distance from the surface increases)
• When the bed tumbles it dilates, allowing the particles to move
downward under gravitational force, and so diffusive mixing occurs
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 Twin shell blender or V cone blender
• It is V shaped and made up of stainless steel or transparent plastic.
• Material is loaded through shell hatches and emptying is normally
done through and apex port.
• material is loaded approximately 50-60% of the total volume.
Small models – 20 kg , rotate at 35rpm
Large models – 1 ton, rotate at 15rpm
• As the blender rotates , the material undergoes tumbling motion.
• When V is inverted, the material splits into two portions. This process
of dividing and recombining continuously yields ordered mixing by
mechanical means.
• https://youtu.be/bo3Vi2H7pKk
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 Double cone blender
• It consists of double cone on rotating shaft.
• usually used for small amount of powders
• efficient for mixing powders of different densities.
• Material is loaded and emptying is done through the
same port.
• The rate of rotation should be optimum depending
upon the size, shape of the tumbler and nature of
the material to be mixed
• Mixing occurs due to tumbling motion.
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 1- Tumbling mixer
Advantages: Disadvantages:
• Good for free flowing powders/granules • Less effective for cohesive/poorly
flowing powders
• Mix from approximately 50 g (Laboratory
scale) to over 100 kg (Large scale) • Segregation is likely to occur if there
are significant differences in particle
• Easy to clean, load and unload size
• Can be used to produce ordered mixes
• Used in the blending of lubricants,
glidants or external disintegrants with
granules prior to tableting
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 Agitator Mixers
• Mixers of this type employs a stationary container to hold the
material and mixing is done by means of mixing screws, paddles or
blades
• well known mixers of this type include the following:
1. The ribbon blender/Mixer
2. Planetary mixer
3. Sigma blade mixer

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 2-Ribbon blender
• Principle:
• Mechanism of mixing is shear.
• Shear is transferred by moving blades. High shear rates are effective in
breaking lumps and aggregates.
• Convective mixing also occurs as the powder bed is lifted and allowed
to cascade to the bottom of the container. An equilibrium state of
mixing can be achieved.

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 2-Ribbon blender
• Construction:
• Consists of horizontal cylindrical trough usually open
at the top.
• It is fitted with two helical blades, which are mounted
on the same shaft through the long axis of the trough.
• Blades have both right and left hand twists &
connected to fixed speed drive.
• It can be loaded by top loading and emptying is done
through bottom port or
• inverting them. 23

• https://youtu.be/tpt5VerLSsg
 2-Ribbon blender
• Advantages • Disadvantages
• High shear can be applied by using • It is a poor mixer, because
perforated baffles, which bring movement of particles is two
about a rubbing and breakdown dimensional.
aggregates.
• Shearing action is less than in
• Headroom requires less space. planetary mixer.
• Dead spots are observed in the
mixer, though they are minimum.
• It has fixed speed drive
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 3-Sigma blade mixer
• primarily used for liquid – solid mixing, although it can be used for solid – solid mixing
• Used in the wet granulation process in the manufacture of tablets, pill masses and
ointments
• Principle–shear. Inter meshing of sigma blades creates high shear and kneading action
• Construction
• It consists of double tough shaped stationary bowl.
• Two sigma shaped blades are fitted horizontally in each tough of the bowl.
• These blades are connected to a fixed speed drive.
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 3-Sigma blade mixer
• working:
• Mixer is loaded from top and unloaded by tilting the
entire bowl.
• The blades move at different speeds , one about twice
than the other, which allows movement of powder
from sides to centers
• The material also moves top to downwards and gets
sheared between the blades and the wall of the tough
resulting cascading action.
• Perforated blades can be used to break lumps and
aggregates which creates high shear forces.
• The final stage of mix represents an equilibrium state.
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 3-Sigma blade mixer
• Advantages • Disadvantages
1. Sigma blade mixer creates a 1. works at a fixed speed
minimum dead space during 2. Chances of entrapment of air
mixing. in the mixing od semisolids
2. It has close tolerances between
the blades and the sidewalls as
well as bottom of the mixer
shell.

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 4-Planetary mixer
• Low speeds are used for dry blending and fast for wet granulation
• Principle:
• Mechanism of mixing is shear. Shear is applied between moving blade
and stationary wall. Mixing arm moves around its own axis and
around the central axis so that it reaches every spot of the vessel.
• The plates in the blades are sloped so that powder makes an upward
movement to achieve tumbling action also.

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 4-Planetary mixer
• Construction:
• Consists of vertical cylinder shell which can be removed.
• The blade is mounted from the top of the bowl. Mixing
shaft is driven by planetary gear and is normally built
with variable speed drive.
• Working:
• The ingredients to be mixed are placed into the vessel and
the blade is allowed to rotate.
• As the motion of the blade is planetary, it reaches to each
and every part of the vessel and mixing is achieved due to
the shear development between the blade and the vessel
wall.
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 4-Planetary mixer
• Advantages: • Disadvantages:
1. Speed of rotation can be varied 1. Mechanical heat is buildup
at will. within the powder mix.
2. Avoid dead zones and vortex 2. It requires high power.
formation 3. It has limited size and is useful
3. More useful for wet granulation for batch work only
process

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 5- Fluidized bed mixer
• Most widely used for mixing granules and powders. Also used in wet granulation process
• Principle:
• Mixing is achieved due to high pressure air stream which produces tumbling action, as a
result of which particles undergoes spiral movements. Air is introduced from the bottom
due to which particles undergoes a fluidized state i.e., the state in which the particles
remains in the air.
• Working:
• The material is placed in fluidized chamber through the feed inlet. The air flows from the
bottom to the top with a high velocity as a result the particles get suspended in the air
stream and fluidization is attained.
• Each particle is surrounded by air, due to which effective drying is achieved.
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 6-Barrel type mixer
• Principle and working
• Mixing is achieved mainly by tumbling action.
• Baffles present, facilitates vigorous mixing by subjecting the movement of
powder towards opposite direction.
• The cylinder is allowed to rotate with the help of motor, following by slow
introduction of powder ingredients through the inlet
• Due to continuous movement of cylinder, tumbling action is created which
facilitates the movement of powder towards the discharge end

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 6-Barrel type mixer
• The baffle present at the discharge end directs the mixture to the
outlet.
• Here the feed introduction and product collection can be done without
stopping the cylinder. Hence, this process is mostly suitable for
continuous operation

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 7-Zig- zag type mixer
• Principle and working
• Mixing is achieved mainly by tumbling action. The ingredients to be
mixed are placed into the zig zag channel as a result of tumbling
action, the ingredients are mixed.
• This movement is caused because of the rotation of mixer vessel as in
the case of a zig zag continuous mixer. This is achieved through
controlled movement of material from the feeding point to the
discharge point.

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 Mixing of semisolids
• Semi solids dosage forms include ointments, pastes, creams, jellies, etc.,
while mixing such dosage forms , the material must be brought to the
agitator or the agitator must move the material throughout the mixer.
• The mixing action include combination of low speed shear, smearing,
wiping, folding, stretching and compressing.
• A large amount of mechanical energy is applied to the material by moving
parts. Sometimes a part of the supplied energy appears as heat.
• The forces required for efficient mixing are high and consumption of power
is also high. Hence the equipment must be rugged constructed to tolerate
these forces.
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 Mixing of semisolids
• Some semisolids exhibit dilatant property i.e., viscosity increases with
increase in shear rates. Therefore, mixing must be done at lower
speeds.
• The speed must be changed accordingly to thixotropic, plastic and
pseudo plastic materials.

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 Mixing equipment
1. Agitator mixers:
Sigma mixers
Planetary mixer
2. Shear mixers:
Triple roller mill
Colloidal mill

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 Mixing equipment
• Selection of mixing equipment
I. Physical properties of the materials – density viscosity and
miscibility
II. Economic considerations regarding processing – time required for
mixing and power consumption
III.The cost of equipment and its maintenance.

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 Triple roller mill
• Principle:- High shear , which causes crushing of aggregates, particles and
also distributes the drug uniformly throughout the semi solid base.
• Construction and working
• It consists of 3 parallel rollers of equal diameters made up of stainless steel.
These are mounted on rigid frame work horizontally.
• The gap between the first 2 rollers is more than that of the gap between the
last two.
• A hopper is placed in between the first two rollers.
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 Triple roller mill

• A scrapper is attached to the last roller.

• First roller rotates at lower speed
compared to the 2nd similarly 2nd
roller speed is less than the 3rd roller.
• https://youtu.be/e14pOIxsx4w

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 Triple roller mill
Advantages 4. Avoid contamination - Through the
selection of materials for the rollers and
1. From the small to the large scraper knives, which are available in a
2. Excellent temperature control broad spectrum of chrome-plated steel,
aluminium oxide, zirconium oxide, and
Three roll mills enable excellent silicon carbide, it is possible to avoid
control of the product temperature, since product contamination due to metal
the product is processed as a thin film on abrasion
the roller. This way, the product can be
warmed or cooled off depending on your 5. Extremely uniform dispersion is
requirements. obtained
3. low material loss

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