Mixing

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 Objectives

At the end of this sub-topic, the student will be able

to:
 Define mixing
 Describe the applications of mixing
 Discuss the mixing of different dosage forms
 Solid/Fluid/semi-solid mixing

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 What is mixing?
Mixing is one of the most common pharmaceutical
operations.
It is difficult to find a pharmaceutical product in which mixing
is not done at one stage or the other during its manufacturing.
Definition
Mixing may be defined as the process in which two or more
than two components in a separate or roughly mixed condition
are treated in such a way so that each particle of any one
ingredient lies as nearly as possible to the adjacent particles
of other ingredients or components.

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 Mixing...
Applications in pharmaceutical industries :
To make uniform physical mixture of powders or granules in
the production of tablets, capsules and dry powders
In case of emulsions and creams, two immiscible liquids are
mixed where one liquid is dispersed into other.
In suspension and pastes solid particles are dispersed in a
liquid by mixing.
In case of dissolving a solid in a solvent mixing makes the
process rapid.

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 Mixing...
Some of the examples of large scale mixing practiced in
pharmacy are:
Mixing of powders in varying proportions prior to
granulation or tabletting
Dry mixing of the materials for direct compression in
tablets
Dry blending of powders in capsules
Blending of powders in cosmetics in the preparation of
face powders, tooth powders
Mixing of two immiscible liquids for preparation of
emulsions.
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 Types of Mixtures

Mixtures may be classified as follows:

1. Positive mixtures

2. Negative mixtures

3. Neutral mixtures

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 Types of Mixtures...

Positive Mixtures
These types of mixtures are formed when two or more
than two gases or miscible liquids are mixed together
by means of diffusion process.
No energy is required for mixing
These types of materials do not create any problem in
mixing
 there is no probability of demixing

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 Types of Mixtures...
Negative Mixtures
These types of mixtures are formed when insoluble
solids are mixed with a vehicle to form a suspension or
when two immiscible liquids are mixed to form an
emulsion.
These mixtures are more difficult to prepare
Require a higher degree of mixing with external force
as there is tendency of the components of these
mixtures separate out unless they are continuously
stirred.

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 Types of Mixtures...
Neutral Mixtures
Many pharmaceutical products such as pastes,
ointments and mixed powders are the examples of
neutral mixtures.
They are static (Not in physical motion) in their
behavior.
The components of such products do not have any
tendency to mix spontaneously
 but once mixed, they do not separate out easily.

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 Mechanism of powder mixing
In order that powders may be mixed, the powder
particles need to move relative to each other
There are three main mechanisms by which
powder mixing occurs:
Convection
Shear
Diffusion

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 Mechanism of powder mixing…
Convective mixing
Convective mixing arises when there is the
transfer of relatively large groups of particles
from one part of the powder bed to another,
as might occur when a mixer blade or paddle
moves through the mix.
This type of mixing contributes mainly to the
macroscopic mixing of powder.

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 Mechanism of powder mixing…

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 Mechanism of powder mixing…

Mixing does not occur within the group

of particles moving together as a unit, and
so in order to achieve a random mix an
extended mixing time is required.

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 Mechanism of powder mixing…
Shear mixing
Shear mixing occurs when a 'layer' of
material moves/flows over another
'layer'.

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 Mechanism of powder mixing…

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 Mechanism of powder mixing…

Diffusive mixing
During this mixing, the materials are tilted/departed so
that the gravitational forces cause the upper layers to
slip and diffusion of individual particles take place over
newly developed surfaces.
Diffusion is also sometimes referred to as micromixing.

NB: All three mixing mechanisms are likely to occur in

a mixing operation.

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 Mechanism of powder mixing…

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 Factors affecting mixing processes

1. Particle-size effects
A difference in the particle sizes of
components of a formulation is the main cause
of segregation (de-mixing) in powder mixes in
practice
There are three types of segregation
Percolation segregation
Trajectory segregation
Elutriation segregation

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 Factors affecting mixing processes...
Percolation segregation
Smaller particles tend to fall through the voids
between larger ones and so move to the bottom of
the mass

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 Factors affecting mixing processes...
Trajectory segregation
During mixing, larger particles will tend to have
greater kinetic energy imparted to them (owing to
their larger mass) and therefore move greater
distances than smaller particles before they come to
rest.
This may result in the separation of particles of
different size, an effect referred to as trajectory
segregation.

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 Factors affecting mixing processes…
Elutriation segregation
During mixing very small particles ('dust') in a mix may
tend to be 'blown' upwards by turbulent air currents as
the mass tumbles, and remain suspended in the air.
When the mixer is stopped, these particles will sediment
and subsequently form a layer on top of the coarser
particles.
This is called elutriation segregation and is also
referred to as 'dusting out'.

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 Factors affecting mixing processes…

2. Particle-density effects
If components are of different density, the more
dense material will have a tendency to move
downwards even if the particle sizes are similar.
Trajectory segregation may also occur with
particles of the same size but different densities,
owing to their difference in mass.
Segregation will be potentiated if the more dense
particles are also smaller.

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 Factors affecting mixing processes…

3.Particle-shape effects
Spherical particles exhibit the greatest flowability
and are therefore more easily mixed,
 but they also segregate more easily than non-spherical particles

Irregularly or needle-shaped particles may become

interlocked, reducing the tendency to segregate once
mixing has occurred.

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 Factors affecting mixing processes…
4.Cohesivity
Cohesive powder is a situation in which the
adhesive forces (mechanical, electrostatic, Van der
Waals ) b/n particles is higher.
Highly cohesive powders are more difficult to blend
than free-flowing materials.
Cohesive powders often requires the application of
external stress to achieve uniformity

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 Factors affecting mixing processes…

5.Humidity and temperature

High level of moisture can accelerate the
formation of agglomerates.
Heating can cause softening of particles, which
can in turn increase cohesion and result in the
formation of agglomerates.

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 Factors affecting mixing processes…

Solution to segregation problem

• Changing the particle size distribution
Increase the cohesive strength of the material
 Too free flowing powders experience segregation problem;
that is the blends have little or no cohesive strength.
 Moderately cohesive materials are preferred
Changing the process and equipment
 Minimize the number of material transfer steps
 With each transfer steps and movement, the tendency for
segregation increases.

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 Type of mixers

1. Mixer for powders

 Tumbling mixers
Agitator mixers
a)Tumbling mixers/blenders
Tumbling mixers are commonly used for
the mixing/blending of granules or free-
flowing powders.

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 Type of mixers...

There are many different designs

Double-cone mixers
Twin-shell mixers
Cube mixer
Y-cone mixers

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 Type of mixers...

Mixing containers are generally mounted so that they

can be rotated about an axis

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 Type of mixers...

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 Type of mixers...

Double-cone mixers

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 Type of mixers...

Cube mixers

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 Type of mixers...

Twin-shell mixers

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 Type of mixers...

Features of tumbling mixers

Minimal attrition when blending fragile granules.
Large-capacity equipment available.
It is easier to clean and unload the blender
Minimal maintenance is required
Available in various capacities from 25 L to 1000 L

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 Type of mixers...

b) Agitator mixers
This type of mixer depends on the motion
of a blade or paddle through the product
E.g. Ribbon mixer
Mixing is achieved by the rotation of
helical blades.

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 Type of mixers...

Advantages of Ribbon Blender

can be designed to operate in both batch and continuous
modes
It is best suited for free flowing and cohesive products.

Disadvantages of Ribbon Blenders

It is not used for fragile materials
It is not suitable for sticky materials
Grinding of material may occur

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 Type of mixers...
2. Mixers for liquids
Mixing mechanisms for fluids fall into four categories;
Bulk transport, turbulent flow, laminar flow and molecular
diffusion
Bulk transport:
 movement of relatively large portion of the material being
mixed from one location in the system to another.
 Eg. Accomplished by means of paddles, revolving blades
or other devices within the mixer arranged to move
adjacent volumes of the fluid in d/t directions

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 Type of mixers...

Turbulent mixing:
 random fluctuation of the fluid velocity at any given
point with in the system produces randomization of fluid
particles
 Highly effective mechanism for mixing
Laminar mixing/streamline:
 frequently encountered when highly viscous fluids are
being processed or if stirring is gentle
 velocity component at any point in the system remains
constant

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 Type of mixers...

Molecular diffusion:
 the diffusion resulting from thermal motion of the
molecules result in mixing
 Diffusion occurs, for example, at the interface between
dissimilar fluids which has been generated by laminar
flow
 May require considerable time to become homogeneous

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 Type of mixers...

Mixers for liquids

Miscible liquids are most commonly mixed by
impellers rotating in tanks.
based on shape and pitch, impellers are mainly
classified as
Paddles
Propellers
Turbines

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 Type of mixers...

a) Paddle Mixers
Their blades have large surface area
Pass close to the thank walls, hence effectively mix viscous
liquids or semisolids
There are various designs for different applications

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 Type of mixers...

Suitable for mixing miscible liquids of low

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viscosity
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 Type of mixers...

Suitable for mixing liquids of higher viscosity

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 Type of mixers...

It is useful for working across a heat transfer

surface
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 Type of mixers...

b) Propeller Mixers
Propellers are commonly used for mixing
miscible and immiscible liquids of low
viscosity.

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 Type of mixers...

A vortex forms when the centrifugal force

imparted to the liquid by the propeller blades
causes it to back up around the sides of the
vessel and create a depression at the shaft.
As the speed of rotation is increased air may be
sucked into the fluid by the formation of a
vortex;
 this can cause possible oxidation

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 Type of mixers...

To avoid vortex formation

Off-set/counterbalance the propeller shaft
from the center
The shaft may enter from the side of the
vessel
fit vertical baffles/A flat plate that controls
or directs the flow of fluid into the vessel

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 Type of mixers...
c) Turbine mixers:
 The blades do not have a constant pitch throughout their
length
 Turbines with tilted blades produce axial flow similar to
propellers
 Due to their rugged design, they are effective for mixing
viscous liquids

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 Type of mixers...
3. Mixers for semisolids
The problems that arise during the mixing of
semisolids (ointments and pastes) stem from the
fact that, unlike powders and liquids, semisolids
will not flow easily.
For this reason, suitable mixers must have
rotating elements with narrow clearances
between themselves and the mixing vessel wall
and they must produce a high degree of shear
mixing
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 Type of mixers...
a) Sigma-blade mixer
Sigma mixer contains mixing element (Blades) of
Sigma type which contra rotates inward to achieve end
to end circulation and thorough and uniform mixing at
close or specified clearance with the container

Sigma-blade mixer

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 Type of mixers...

b) Planatory Mixer

Different blade attachment available for

Planatory Mixer planetary mixer

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 Thank you…….

Q?

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