MIXING

Definition:

Mixing is defined as a process that tends to result in a randomization of

dissimilar particles within a system.

The term mix means to put together in one mass or assemblage

with more or less thorough diffusion of the constituent elements among
one another.

The term blending means to mix smoothly and inseparably

together.
 OBJECTIVES

1. To produce single physical mixture:

• This may be simply the production of a blend of two or more miscible
liquids or two or more uniformly divided solids.

2. To produce physical change:

• Mixing can be performed to produce physical as well as chemical change,
for example, solution of a soluble substance.
• In such cases a lower efficiency of mixing is often acceptable because
mixing merely accelerates a dissolution and diffusion process that could
occur by simply agitation.
3. To produce dispersion:
• Mixing is also aimed to include dispersion of two immiscible liquids
to form an emulsion OR dispersion of a solid in liquid to give a
suspension or paste.
• Usually good mixing is required to ensure stability and effectiveness.

4. To promote chemical reaction:

• Mixing encourage and at the same time control a chemical reaction.
 APPLICATIONS
Mixing is involved in the preparation of many types of formulations.
Mixing is also an intermediate stage in the production of several dosage forms.

1. Wet mixing in the granulation step in the production of tablets and

capsules.

2. Dry mixing of several ingredients ready for direct compression as in

tablets.

3. Dry blending of powders in capsules, dry syrups and compound powders

(insufflations).
 In the manufacture of tablets

normally a number of additives are added

Therefore mixing of powders becomes an essential part of the process

When the dose of the active substance is high (for eg: paracetamol tablets)

mixing is not a problem

But in case of potent drugs and low dose drugs,

high amounts of adjuvants (for example lactose) are added.

Therefore, mixing is considered as a critical factor. Otherwise, content uniformity of
 FACTORS AFFECTING MIXING
1. Nature of the surface:
Rough surface of one of the components does not induce satisfactory mixing

This can be due to the entry of active substance into the pores of the other
ingredients

Adding a substance, which will be adsorbed on its surface

can decrease aggregation

Eg: addition of aerosil (colloidal silicon dioxide) to zinc oxide.

Thus, a strongly aggregating zinc oxide becomes a fine dusting powder.
which can be mixed easily.
2. Density of particles:
Demixing is accelerated when

the density of the smaller particle is higher

This is due to the fact - that dense material always moves downward and settles at
the bottom
3. Particle size:
It is easy to mix two powders having approximately the same particle size
The variation of the particle size can lead to separation

because the small particles move downward through the spaces between the bigger
particles.
The powders with mean particle size of less than 100 µm are free flowing, which
facilitates mixing.
4. Particle Shape: The ideal particle is spherical in shape for the purpose of
uniform mixing.

5. Particle Charge: Some particles exert attractive forces due to electrostatic

charges on them. This can lead to separation or segregation.

6. Proportion of materials: The best results can be obtained if two powders

are mixed in equal proportion by weight and by volume.
If there is a large difference in the proportion of two powders

mixing is always done in the ascending order of their weights.

 LIQUID MIXING SOLID MIXING
Flow currents are responsible for Flow currents are not possible.
transporting unmixed material to the
mixing zone adjacent to impeller.

Truly homogeneous liquid phase can be Product often consists of two or more
observed easily identifiable phases

Small sample size is sufficient to study Large sample size is required

degree of mixing

Requires low power Requires high power

MECHANISM OF SOLID-SOLID MIXING

The principal mechanisms in solid-solid mixing are:

1. CONVECTIVE MIXING

2. SHEAR MIXING

3. DIFFUSIVE MIXING
1. CONVECTIVE MIXING:

• Achieved by the inversion of the powder by using blades or paddles or

screw element.

• A large mass of material moves from one part to another.

• Convective mixing is referred to as Macromixing.

2. SHEAR MIXING

• The forces of attraction are broken down so that each particle moves on
its own between regions of different composition and parallel to their
surface.

• In a particulate mass, the forces of attraction are predominating which

make the layer slip over one another.

• Such types of attraction forces are predominant among same type of

particles.

• Shear force reduces these attraction reduce the scale of segregation.

3. DIFFUSIVE MIXING

• It involves the random motion of particles within the powder bed,

thereby particles change their positions relative to one another.

• Diffusive mixing occurs at the interfaces of dissimilar regions.

• Diffusion is sometimes referred to as micro-mixing.

In the solid-solid mixing operations, four steps are involves.

These are:
1. Expansion of the bed of solids

2. Application of 3-dimensional shear forces to the powder bed.

3. Mix long enough to permit true randomization of particles.

4. Maintain randomization.
The law of mixing appears to follow first order,

𝑴 = 𝑨 (𝟏 − 𝒆 −𝒌𝒕)
Where,
M = degree of mixing after time t,
T = time
A and k = constants

A and k depends on the - Mixer geometry

Physical characteristics of the powders and
Proportion of the material being mixed
 DEGREE OF MIXING

1. IDEAL MIXING (PERFECT MIXING)

2. ACCEPTABLE MIXING
a) Random mixing
b) Ordered mixing – Mechanical means of ordered mixing
Adhesion means of ordered mixing
Coating means of ordered mixing
 STATISTICAL PARAMETERS
1. Arithmetic mean:
Size distribution is calculated.

2. Standard deviation:
Used to know the spread of dispersion.
 MIXING INDICES

Involves the comparison of SD of sample of a mixture under study with

the estimated standard deviation of a completely random mixture.
It can be expressed -
 CLASSIFICATION OF EQUIPMENT FOR SOLID MIXING

A. Based on flow properties:

1. Free flowing solids: e.g.: V cone blend , Double cone blender
2. Cohesive solids: e.g.: Sigma blender, Planetary mixer

B. Based on scale of mixing:

1. Batch type (small scale): e.g.: Mortar and pestle, V cone blender, Double
cone blender, Ribbon blender, Sigma blender, Planetary paddle, Fluidized
mixer
2. Continuous type (large scale): e.g.: barrel type, zigzag type
Sr. Nature of mixer Examples Mechanism of
no mixing
1 Batch type (small scale) Mortar pestle Trituration

2 Tumbling mixers without mixing Double cone blender Tumbling action

blade and V cone blender
without baffles
3 Tumbling mixer with a mixing blade Double cone blender Tumbling action as
and V cone blender well as shearing with
with mixing blades blade

4 Static mixers Ribbon blender Sigma Stationary shell and

blender Planetary rotating blade
paddle
5 Air mixers or fluidized mixers Fluidized mixer Air supported
blending
6 Continuous type Barrel type Zigzag Rotating shell with
type rotating blade
 V CONE BLENDER (TWIN SHELL BLENDER)
Mechanism of mixing: Tumbling action
Construction:

1. Made of either stainless steel or transparent plastic.

2. Smaller models - take a charge of 20 kg and rotate at 35 rpm (revolutions

per minute)
3. Larger models - takes a charge of about 1 tonne and rotate at 15rpm.

4. The material is loaded through either of the shell hatches.

5. Emptying of the blend is normally done through an apex port.

Working:

The material (to be blended),is loaded approximately 50 to 60 % of its

total volume

As the blender rotates, the material undergoes tumbling motion

When the V is inverted the material splits into two portions

This process of dividing and recombining continuously yields ordered

mixing by mechanical means.
 Blender speed is the key for mixing efficiency

At high speeds more dusting or seggregation of fines is possible

At low speeds not enough shear may be applied

Advantages:

1. If fragile granules are to be blended twin shell blender is suitable

because of minimum attrition.

2. They handle large capacities.

3. Easy to clean load and unload.

4. Requires minimum maintenance.

Disadvantages:

1. Twin shell blender needs high headspace for installation.

2. Serial dilution is required for the addition of low dose active

ingredients.
 DOUBLE CONE BLENDER
• It is usually charged and discharged through the same port.

• It is an efficient design for mixing powders of different densities.

• These are used mostly for small amounts of powders.

•
• The rate of rotation should be optimum depending on the size and shape of the tumbler
nature of material to be mixed.

• Commonly the range is 30 to 100 revolutions per minute.

(Working, Advantages and Disadvantages - remains same as that of the V-cone

blender)
 RIBBON BLENDER
Mechanism of mixing: SHEAR

Shear is transferred to the powder bed by moving blades(ribbon

shaped) in a fixed (non- movable) shell

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

Note: Shear is caused by one force pushing part of a mixture while another force
pushes a different part of mixture in opposite direction.
Construction:
1. It consists of a non-movable horizontal cylindrical trough (shell) usually
open at the top.

2. It is fitted with two helical blades, which are mounted on the same shaft
through the long axis of the trough.

3. The blades have both right and left hand twists.

4. The blades are connected to a fixed speed drive.

5. Ribbon blender is top loading with a bottom discharge port.

6. The trough can be closed with a lid.

Working:
Powders are introduced from the top of the trough

Through the fixed speed drive ribbons are allowed to rotate

One blade moves the solids slowly in one direction and

the other moves them quickly in opposite direction

The body is covered because

considerable dust may be evolved during dry blending and granulating

solution may evaporate during wet granulation
The powders are lifted by a centrally located vertical screw and allowed
to cascade to the bottom of the container (tumbling action)

The counteracting blades set up high shear and are effective in breaking
up lumps or aggregates

Helical blades move the powders from one end to another

The final stage of mix represents an equilibrium state

The blend is discharged from the bottom opening

Applications:

1. Used to mix finely divided solids, wet solids mass, sticky and plastic
liquids.

2. For liquid-solid and solid-solid mixing.

Advantages:
1. High shear break down aggregates.

Disadvantages:
1. It is a poor mixer because movement of particles is two-dimensional.

2. Dead spot (areas that remain unmixed) are observed.

3. Works at a fixed speed.

 SIGMA BLADE MIXER

Mechanism of mixing: SHEAR

The inter-meshing of sigma shaped blades

creates high shear and kneading actions

Convective mixing is achieved by cascading the material.

Construction:
1. It consists of a trough shaped stationary bowl.

2. Two sigma (indicating the shape of the Greek letter) shaped blades
are fitted horizontally in each trough of the bowl.

3. These are connected to a fixed speed drive.

4. The mixer is loaded from the top and unloaded by tilting the entire
bowl by means of a rack-and-pinion drive.
Working:
Powders are introduced from the top of the trough

The body is covered because dust may be evolved during dry blending
and granulating solution may evaporation during wet granulation

Through the fixed speed drive the sigma blades are allowed to rotate

The blades rotate at different speeds

One usually about twice the speed of other

Resulting in lateral pulling of the material

Blades turn towards each other so that the powders move from the sides to the
centre of the bowl

The material further moves from the top to downwards over the point and then
sheared between the blades and the wall of the trough

Thus cascading action (convective) as well as shear action can be achieved

By means of a rack-and-pinion drive the bowl is tilted to empty the blend

Applications:

1. It is used in wet granulation process in the manufacture of tablets,

pill masses and ointments.

2. Primarily used for liquid-solid mixing.

Advantages:

1. Creates a minimum dead space during mixing.

Disadvantages:

1. Works at a fixed speed.

 PLANETARY MIXER
Principle:
The blade tears the mass apart and shear is applied between a moving
blade and a stationary wall

The mixing arm moves in two ways around its own axis and around the
central axis so that it reaches every spot of the vessel

The plates in the blade are sloped so that the powder makes an upward
movement

Therefore, tumbling (convective) motion is also obtained

Construction:
1. It consists of a vertical cylindrical shell, which can be removed
either by lowering it beneath the blade or raising the blade above the
bowl.

2. The mixing blade is mounted upon the top of the bowl.

3. The mixing shaft is driven by a planatery gear.

4. It rotates around the ring gear, which further rotates round the mixer
blade.
Working:
Agitator has a planetary motion

It rotates on its own and around the central axis so that it reaches all
parts of the vessel

Beater is shaped to pass over the side and bottom of the mixing bowl

Therefore, there are no dead spaces in the mixing bowl

The blade tears the mass apart and shear is applied between the moving
blade and the stationary wall

The plates in the blade are sloped so that the powder makes an upward
movement

Therefore, tumbling (convective) motion is also obtained

Emptying the bowl may be done by hands (scooping) or by dumping

mechanism.
Applications:

1. Low speeds are used for dry blending and faster speeds for wet
granulation.

2. Steam jacketed bowls are used in the manufacture of sustained

release products and ointments.
Advantages:
1. Speed of the rotation can be varied.
2. No dead space.

Disadvantages:
1. Mechanical heat is built up within the powder mix.
2. Requires high power.
3. For batch process only.
 MECHANISM OF LIQUID-LIQUID MIXING
1. Bulk transport:
Movement of large portion of a material from one location to another
location in a give system.
Rotating blades and paddles are used.

2. Turbulent mixing:
Highly effective, mixing is due to turbulent flow which results in
random fluctuation of the fluid velocity at any given point within the
system.
Fluid velocity at a given point changes in 3 directions (X, Y and Z).
3. Laminar mixing:
Mixing of two dissimilar liquids through laminar flow, i.e., applied
shear stretches the interface between them.
Suitable for liquids which require moderate mixing.

4. Molecular diffusion: Mixing at molecular level in which molecules

diffuse due to thermal motion.
General Equipment For Liquid Liquid Mixing
 Mixing Device - IMPELLERS

Based on shape and pitch, they are classified into 3 types,

1. PROPELLERS

2. TURBINES

3. PADDLES
 PROPELLERS

• A three bladed design is the most common for liquids.

• Propellers may be either right or left handed, depending on the direction
of slant of their blades.
For deep tank - Two are more propellers are used.

These work in opposite directions to create a zone of high turbulence.

For low viscous liquids - Size of propeller is smaller.

Small size propellers can rotate up to 8000rpm and produce longitudinal
movement.

For large tanks - propeller size increased upto 0.5 metres maximum.
Advantages of propellers:
1. Used when high mixing capacity is required.
2. Effective for liquids which have maximum viscosity of 2.0 pascals.sec
or slurry up to 10% solids of fine mesh size.

Disadvantages of propellers:
1. Propellers are not normally effective with liquids of viscosity greater
than 5pascal.second such as glycerin castor oil.
 TURBINES
• A turbine consists of a circular disc to which a number of short blades are
attached.

• Blades may be straight or curved.

• The diameter of the turbine ranges from 30-50% of the diameter of the vessel.

• Turbines rotates at a lower speed than the propellers (50-200rpm).

• Flat blade turbines - produce radial and tangential flow but as the speed
increases radial flow dominates.
• Pitched blade - turbine produces axial flow.
 Shear produced by turbines can be further enhanced by

using a diffuser ring (stationary perforated ring which surrounds the

turbine)

Diffuser ring increase the shear forces as liquid passes through the
perforations
Advantages of turbines:
1. Suitable for emulsification.

2. Effective for high viscous solutions with a wide range of viscosities

up to 7.0 Pascal. Second

3. They can handle slurries with 60% solids.

 PADDLES
• A paddle consists of a central hub with long flat blades attached to it
vertically.

• Two blades or four blades are common sometimes the blades are pitched
and may be hemispherical in shape.

• Paddles rotates at a low speed of 100rpm.

• They push the liquid radially and tangentially with almost no axial
action unless blades are pitched.
Advantages of paddles:
1. Paddles are used in the manufacture of antacid suspensions, agar and
pectin related purgatives, antidiarrheal mixtures such as bismuthkaolin.

2. Vortex formation is not possible because of low speed mixing.

possible with paddle.

Disadvantages of paddles:
1. Mixing of the suspension is poor (therefore baffled tanks are
required)
 MIXING OF IMMISCIBLE LIQUID
1. SILVERSON EMULSIFIER

2. COLLOIDAL MILL

3. RAPISONIC HOMOGENIZER

• Mixing of immiscible liquids is carried 'in pharmacy ' mainly in the manufacturing of
emulsions.
• The equipment used for the preparation of an emulsion is known as emulsifier
• Fine emulsion can be obtained and therefore, equipment is known as homogenizer
 SILVERSON EMULSIFIER
Principle:
It produces intense shearing forces and turbulence

by use of high speed rotors.

Circulation of material takes place through the head by the suction

produced in the inlet at the bottom of the head.

Circulation of the material ensures rapid breakdown of the dispersed

liquid into smaller globules.
Construction:
1. It consists of long supporting columns connected to a motor which
give support to the head.

2. The central portion contains a shaft one end of which is connected to

the motor and the other end is connected to the head.

3. The head carries turbine blades.

4. The blades are surrounded by a mesh, which is further enclosed by a

cover having openings.
Working:
The emulsifier head is placed in the vessel containing immiscible
liquids (or coarse emulsion) in such a way that it should get completely
dipped in the liquid

When the motor is started the central rotating shaft rotates the head

which in turn rotates turbine blades at a very high speed

This creates a pressure difference

As a result, liquids are sucked into the head from the center of the base
and subjected to intense mixing action.
 Centrifugal forces expel the contents of the head with great force
through the mesh and onto the cover

As a result a fine emulsion emerges through the openings of the outer

cover

The intake and expulsion of the mixture

set up a pattern of circulation to ensure rapid breakdown of the bigger

globules into smaller globules.
Uses:
1. Used for the preparation of emulsions and creams of fine particle size.

Advantages:
1. Silver son mixer is available in different sizes to handle the liquids
ranging from a few milli liters to several thousand liters.
2. Can be used for batch operations as well as for continuous operations by
incorporating into a pipeline, through which the immiscible liquids flow.

Disadvantages:
1. Occasionally, there is a chance is clogging of pores of the mesh.