BWU/B.

Pharm/III Semester / Pharmaceutical Engineering

CHAPTER – 8
Mixing

Syllabus:
Mixing: Objectives, applications & factors affecting mixing, Difference between solid and liquid
mixing, mechanism of solid mixing, liquids mixing and semisolids mixing. Principles,
Construction, Working, uses, Merits and Demerits of Double cone blender, twin shell blender,
ribbon blender, Sigma blade mixer, planetary mixers, Propellers, Turbines, Paddles & Silverson
Emulsifier.

Definition
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 unit (particle, molecule etc.) of the components lies as
nearly as possible in contact with a unit of each of the other components.
If this is achieved it produces a theoretical ‘ideal’ situation, i.e. a perfect mix.

Objectives of mixing:
1. To make simple physical mixture
In the production of tablets, capsules, sachets and dry powders two or more powders or granules are
mixed.
In linctuses two or more miscible liquids are mixed completely.
2. Physical change
Mixing may aim at producing a change that is physical, for example the solution of a soluble
substance. In case of dissolving a solid in a solvent mixing will take place by diffusion but the
process will be slow. In this case agitation makes the process rapid.
3. Dispersion
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.
4. Promotion of reaction
Mixing will usually encourage (and control at the same time) a chemical reaction, so ensuring
uniform products.

Application of mixing: Mixing is one of the most common pharmaceutical operations. It is an

intermediate stage in the production of many pharmaceutical dosage forms.
i) Wet mixing is carried out in the production of tablets and capsules.
ii) Dry mixing is done for different excipients used in direct compression of tablet preparation.
iii) Dry blending of powders is done in the preparation of capsules, dry syrup and compound
powders.
iv) For production of pellets for capsules mixing is an important step.

Factors affecting mixing: Flow property of the powders are considered to be one of the important
factors for mixing. However there are many factors that can influence mixing operation, such as-

i) Nature of the surface: Rough surface does not result satisfactory mixing due to the entry of
other substance into the pores present on surface. To overcome this problem, a
substance which can be adsorbed on rough surface can be added. E.g. Strongly
aggregating zinc oxide becomes fine dusting powder when dispensed with aerosil
(colloidal silicon dioxide).
ii) Density of the particles: Demixing occurs when density of smaller particles is higher than
the other substance due to settling tendency of the particles.

1|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

iii) Particle size: Mixing of similar size particles becomes relatively easy. If one sample
particles are relatively smaller then it will have a tendency to settle at the bottom by
passing through the gaps between the bigger particles.
iv) Particle shape: Spherical shape is the ideal shape for mixing. Irregular shape can form
interlock between particles which can result aggregation.
v) Particle charge: The particles exert electrostatic charges can cause either separation or
segregation.
vi) Proportion of materials: When two substance are mixed in equal proportions that gives the
best mixing. If there is a large difference between the proportions of two powders,
mixing should be done in ascending order of their weights.

Solid mixing and liquid mixing:

Liquid Mixing Solid Mixing

Flow currents are responsible for transporting
unmixed material to the mixing zone adjacent to
impeller.
Truly homogenous liquid phase can be
observed.
Small sample size is sufficient to study degree of
mixing.
Mixing requires low power.
Flow currents are not possible
Product often consists of two or more easily
identifiable phases.
Large sample size is required.
Mixing requires high power.

Types of Mixtures
Mixtures may be divided into three types that differ fundamentally in their behavior:

Positive mixtures: Positive mixtures are formed from materials such as gases or miscible liquids,
which mix spontaneously and irreversibly by diffusion and tends to approach a perfect mix. There
is no input of energy required. If enough time is available the mixing is complete. In general, such
materials do not present any problems in mixing.
e.g. Mixing of sodium chloride and sugar in water.

Negative mixtures: In negative mixtures, after mixing, the components will tend to separate out. If
this occurs quickly, then energy must be continuously input to keep the components in dispersed
state. Negative mixtures are more difficult to form and a higher degree of mixing efficiency is
required.
e.g. Calamine lotion.
Neutral mixtures: Neutral mixtures are static in their behavior, the components having no tendency
to mix spontaneously, nor do they segregate when mixed.
e.g. Pastes, ointments and mixed powders.

SOLID-SOLID MIXING

Mechanism of solid-solid mixing

It has been generally accepted that solid mixing proceeds by a combination of one or more of the
following mechanisms:
i. Convective mixing: A relatively large mass of material is moved from one part of the
powder bed to another  this is called convection. Depending on the type of mixer

2|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

employed, convective mixing can occur by an inversion of the powder bed, by means of
blades or paddles, or by means of a revolving screw etc.

ii. Shear mixing: As a result of forces within the particulate mass, slip planes are set up.
Depending on the flow characteristics these can occur singly or in such a way that it give
rise to laminar flow. When shear occurs between regions of different composition and
parallel to their interface, it reduces the scale of segregation by thinning the dissimilar
layers. Shear occur in a direction normal to the interface of such layers is also effective
since it too reduces the scale of segregation.

iii. Diffusive mixing: Mixing by “diffusion” is said to occur when random motion of particles
within a particle bed causes them to change position relative to one another. Such as
exchange of positions by single particles result in reduction of the intensity of segregation.
Diffusive mixing occurs at the interfaces of dissimilar regions that are undergoing shear and
therefore results from shear mixing.

Mixing equipment
 The ideal mixer should produce a complete blend rapidly with as gentle as possible a mixing
action to avoid product damage.
 It should be cleaned and discharged easily,
 be dust-tight and
 require low maintenance and
 low power consumption
 mixers should be earthed to dissipate the static charge on particles.

Tumbling mixers / blenders

Applications: Used for mixing / blending of granules or free-flowing powders.

In tumbling mixers, rotation of the vessel imparts movement to the materials by tilting the powder
until the angle of the surface exceeds the angle of repose when the surface layers of the particles go
into a slide.
A common type of mixer consists of a container of one of several geometrical forms, which is
mounted so that it can be rotated about an axis. The resulting tumbling motion is accentuated by
means of baffles or simply by virtue of the shape of the container.

Rotating -Shell Mixers

The drum type, cubical-shaped, double-cone and twin shell blenders are all examples of this class
of mixers.
Drum-type blenders with their axis of rotation horizontal to the centre of
the drum are used quite commonly.
Disadvantages: This suffers from poor cross flow along the axis.
Remedy:- The addition of baffles or inclining the drum on its axis
increases cross flow and improves the mixing action.

Cubical and polyhedron shaped blenders with the rotating axis set at
various angles also are available.

3|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

Disadvantages:- In the polyhedron type blender, because of their flat surface, the powder is
subjected more to a sliding than a rolling action which is not conducive to the most efficient
mixing.

Double cone blender provides a good cross flow with a rolling rather a
sliding motion. Normally no baffles are required so that cleaning is
simplified.

Twin shell blender combines the efficiency of the inclined drum-type with the intermixing that
occurs when two such mixers combine their flow. The twin-shell blender
takes the form of a cylinder that has been cut in half, at approximately a
450-angle with its long axis, and then rejoined to form a “V”-shape. This is
rotated so that the material is alternatively collected in the bottom of the V
and then split into two portions when the V is inverted.
Mechanism of Action:
This is quite effective because the bulk transport and shear, which occur in tumbling mixers
generally, are accentuated by this design.
A bar containing blades that rotate in a direction opposite to that of the twin shell often is used to
improve agitation of the powder bed, and may be replaced by a hollow tube for the injection of
liquids.
The efficiency of tumbling mixers is highly depended on the speed of rotation.
 If the rotation speed is too slow  does not produce desired tumbling or cascading
motion nor does it generate rapid shear rates.
 If the rotation speed is too high  produce centrifugal force sufficient to hold the powder
to the sides of the mixer and thereby reduce efficiency.
 If the rotation speed is optimum depends on the size, shape, r.p.m. Commonly in the
range of 30 to 100 rpm.

Agitator mixers
Agitator mixer for powders can take a similar form to paddle mixers for liquids, but their efficiency
is low. Planetary motion mixers are effective, but special design are to be preferred.
This type of mixers employs a stationary container to hold the material and brings about mixing by
means of moving screws, paddles or blades.
Use: Since the mixers do not depend entirely on gravity as do the tumblers, it is useful in mixing
wet solids, sticky pastes etc.
The high shear force effectively break up lumps or aggregates.

Ribbon blender

The ribbon blender consists of a relatively long trough-like shell with a hemispherical bottom. The
shell is fitted with a shaft on which are mounted spiral ribbons, paddles or helical screws, alone or
in combination. These mixing blades produce a continuous cutting and shuffling of the powder by
circulating the powder from end to end of the trough as well as rotationally. The shearing action
that develops between the moving blade and the trough serves to break down powder agglomerates.
Disadvantages: They are not precision blenders and they are difficult to clean.

4|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

RIBBON BLENDER

Sigma blade and planetary mixers

Sigma blade and planetary mixers are also used at a step prior Motor
Rotating
to addition of liquid (e.g just before wet massing in tablet wet- arm
granulation). Fig. See semisolid mixers for sigma blenders
and

Conical orbital screw mixer (Nautamixer)

Conical orbital screw mixer consists of a conical vessel fitted Helical
conveyor
at the base with a rotating screw, which is fastened to the end
of a rotating arm at the upper end. Discharge
Working:
The mixer screw rotates at its own axis and simultaneously
moves in the orbit at the periphery of the conical container. It Fig. Conical orbital mixer (Nautamixer)
produces three mixing currents:
(i) The mixer screw rotates to lift the material to the top of the cone.
(ii) The rotating arm guides the whole screw in a circular path along with the periphery of the
conical container so the material is conveyed in a horizontal manner.
(iii)The material drops off the screw to the opposite side of the cone, and is lifted up repeatedly.
The mixer thus combines convective mixing (as the material is raised by the helical conveyor) and
shear and diffusive mixing (as the material cascades downwards).

Advantages: Nautamixer can be jacketed and may be done under vacuum. Nautamixer is used in
mixing powder, wet granulation. It may be used to mix plant products containing mucilage.

LIQUID-LIQUID MIXING
Mechanisms of mixing
The mechanism of mixing of liquids can be studied under four classes. They are:
1. Bulk transport
2. Turbulent mixing
3. Laminar mixing
4. Molecular diffusion
Bulk transport is defined as the movement of a large portion of a liquid from one location to
another location.
Turbulent mixing is defined as mixing due to turbulent flow, which results in random fluctuation of
the fluid velocity at any given point within the system.
Laminar flow is the mixing of two dissimilar liquid through laminar flow, i.e. the applied shear
stretches the interface between them.
Molecular diffusion is the mixing at molecular level in which molecules diffuse due to
thermodynamic motion.

MIXERS:
Liquid mixing is usually performed with a
(i) mixing element, commonly a rotational device, which provides the necessary shear force and
flow,
(ii) a tank either jacketed or not jacketed in which the mixing element will be fitted.

5|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

Mechanism of mixing:
The movement of the liquid at any point in the vessel will have three velocity components and the
complete flow pattern will depend upon variations in these three components in different parts of
the vessel.
The three velocity components are:
(i) Radial component, acting in a direction vertical to the impeller shaft.
(ii) Longitudinal component, acting in a direction parallel to the impeller shaft.
(iii)A tangential component, acting in a direction that is a tangent to the circle of
rotation round the impeller shaft. Radial
A satisfactory flow pattern will depend on the balance of these three
components.
Examples: Assuming that the impeller is placed vertically in a mixing tank.
 Excessive radial movement, especially if solids are present, will take
materials to the container wall, when they fall to the bottom and may rotate
as a mass beneath the impeller. Longitudinal
 If the tangential component is dominant, a vortex forms and may deepen
until it reaches the impeller, when aeration occurs.
 If the longitudinal component is inadequate, liquids and solids may rotate in
layers without mixing, even when rotation is rapid and in the presence of
vortexing. Tangential

Factors affecting the flow pattern of liquids:

(i) Form of impeller and its position; e.g. whether it is high or low in the vessel, whether mounted
centrally or to one side, or whether the shaft is vertical or inclined.
(ii) Container shape.
(iii)Presence of baffles.
(iv) Liquid properties  It has been found that the optimum speed of rotation (v) of the mixing
element and the ratio of the diameter of the container (D), to the diameter of the mixing element
(d) are both inversely proportional to the apparent viscosity () of the liquid.
i.e. v  1/
D/d  1/
 Hence, a liquid of low viscosity will use an impeller with a D/d ratio of the order of 20 and
rotating at high speed.
 A liquid of high viscosity, such as paste, will need a D/d ratio of 1 and low speed of rotation.
i.e., blades of the impellers are used so that they more slowly and scrape the side of the vessel.

MIXING EQUIPMENT FOR LIQUID

PROPELLER MIXERS
 The propellers are small impellers that produce a longitudinal movement of liquids.
 Generally they are small in relation to the container i.e. container diameter to propeller diameter
ratio (D/d)  20.
 They generally operates at high speeds: up to 8000 rpm.
 Propeller mixer is not normally effective with liquids of viscosity greater than about 5 Ns/m 2;
which is some what greater than glycerin or castor oil.

6|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

Vortexing and its remedies:

Due to the high speed of the propellers vortexing and finally aeration
may occur; i.e. air may get entrapped which may be difficult to
remove from the product and the air may encourage oxidation in
some cases.
To avoid vortexing the following strategies can be worked out:
(i) The propeller should be deep into the liquid and [fig (a)] fig (a) fig (b)
(ii) Symmetry should be avoided:
(a) propeller shaft may be off-set from the center. [fig (b]
(b) propeller shaft may be mounted at an angle to the vertical
wall of the container. [fig (c)]
(c) the shaft may enter side of the vessel [fig (d)]
(d) or, a vessel other than cylindrical may be used, (N.B. fig (c) fig (d)
although this is liable to give rise to ‘dead spots’ in corners)
(iii) A push-pull type of propeller may be used in which two
propellers of opposite pitch are mounted on the same shaft so that the
rotating effects are in opposite directions and cancel each other. [fig
(e)]
(iv) One or more baffles may be used which are usually vertical strips fig (e)
attached to the wall of the vessel. [fig (f)]
Use: fig (f)
(i) Propellers are suitable when strong vertical currents are required
e.g. in suspensions of solids in liquids.
(ii) They are not suitable when considerable shear is required, as in emulsification.

TURBINE MIXERS
A turbine mixer uses a circular disc impeller, to which are attached a number of vertical blades,
which may be straight or curved.
Characteristics:
(i) They are usually rotated at a somewhat lower speed than the propeller type.
(ii) D/d ratio is lower than that of propeller type.
(iii)The blades are usually flat, hence, very little axial or tangential flow, the
liquid moves rapidly in a radial direction.
(iv) They give rise to greater shear forces than propeller type and these shear
forces can be increased further by fitting a diffusing ring. This is a stationary
perforated or slotted ring which surrounds the impeller, so that the
discharged liquid must pass through the apertures. The diffuser reduces
rotational swirling and vortexing , but is most useful in increasing shear Turbine type
forces.
(v) They can deal with more viscous liquids than the propeller mixer, having a range upto
100Ns/m2 approximately the consistency of liquid glucose.

7|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

Use:
(i) Suitable for viscous liquids.
(ii) Not suitable for suspensions, because no vertical flow is there.
(iii)The higher shear forces and the greater viscosity range give it a special
application in the mixing of liquids that may stratify with a propeller and,
particularly, in the preparation of emulsions of immiscible liquids.

Paddle mixers Paddle type

Paddle mixers use an agitator consisting usually of flat blades attached to a
vertical shaft and rotating at low speed (100 rpm).
Characteristics:
(i) For liquids of low viscosity simple flat paddles are used and the emphasis is
on radial and tangential movements.
(ii) Paddles for more viscous liquids generally have a number of blades, often Planetary Mixer
shaped to fit closely to the surface of the vessel, avoiding ‘dead spot’ and
deposited solids.
(iii)An alternative design for the more viscous range of liquids is the planetary motion mixer, which
has a smaller paddle that rotates on its own axis, but travels also, in circular path round the
mixing vessel. The agitator is fixed at the side of the vessel, to eliminate ‘dead spots’.
(iv) The width of the agitator is not more than 1/2 to 2/3rd of the diameter of the vessel, which
requires less power than that needed for a full width central agitator, improves the circulation in
the vessel, and increases mixing efficiency.

SOLID-LIQUID MIXING
During tablet granulation binder solution is added to dry powder mass, and a damp mass is formed
which is very difficult to mix with ordinary mixers. So planetary and sigma blenders are used.
Agitator mixers
(i) Planetary motion mixers:

Construction: It consists of a circular base. Inside the Blade

container a blade rotates around its own axis. The axis of
the blade again rotates along a shaft. Thus the motion of
the blade is similar to the motion of a planet around the
sun. The planet is rotating along its own axis and at the
Shaft
same time the planet is rotating around the sun. The
design of the blade is as shown in the figure. There is Container
very little clearance between the blade and the wall of the
container. Fig. Planetary mixer

Working: This design allows the revolving blade to handle (mix) a small amount of mass at a time.
Again the blade is moving, carrying the mass to other places. The blade is scraping the materials
those are sticking to the wall of the container.
Application:
1. This sturdy (strong) mixer is used to mix semisolid ointments.
2. To prepare tablets the powder is mixed with binder solutions. During this wet massing step
planetary mixer is used.

8|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

(ii) Sigma Blender:

Construction:
It uses two mixer blades, the shape of which resembles the Greek letter “sigma” ().The two blades
rotates 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 CROSS-SECTION
material and divisions into two troughs, TOP VIEW
VIEW
while the blade shape and difference in
speed causes end-to-end movement. SIGMA BLENDER
Use:
 This types of mixers are of sturdy construction and high power, hence, they can handle even the
heaviest plastic materials and products like tablet granule, and ointments are mixed readily.
 To reduce the entrainment of air in ointment masses the sigma mixer can be enclosed and
operated under reduced pressure, which is an excellent method for avoiding entrainment of air
and may assist in minimizing decomposition of oxidizable materials, but it must be used with
caution if mixer contains volatile ingredients.
 As with many other mixers, the vessel is jacket for heating or cooling and, in this case, the
blades can be hollow for the same purpose. This can be very useful in practice, since some
semi-solids may be reduced in viscosity by heating, while with other materials it may be
necessary to dissipate the heat resulting from the energy put into the mixing process.

SEMISOLID MIXING
For semisolid mixing planetary and sigma blenders are used to mix the ointment base ingredients,
solids and liquids. Three roll mill is used in mixing solid particles with ointment base.
Three Roll Mill
Mulling mixers are efficient in deaggregation of solids. e.g. A
Roller mills consists of one or more rollers. Of these three
roll type is preferred for semisolid preparations. The rollers Scrapper
B C D
rotate at different speed. The material is placed in the
hopper which then passes through roller B and C. Materials
coming into the rollers are crushed, depending on the gap Cross-section of three roll mill
between the rollers. The gap between C and D (lesser than
the previous one) reduces the particles further and smoothes the mixture. A scrapper continuously
removes the materials from the roller D. Roller C moves to-and-fro along its axis to give a
kneading action. GRINDING
SURFACES

FEED
COLLOID MILL ROTOR
The principle of operation of the colloid
mill is the passage of the mixed phases of
an emulsion formula between a stator and STATOR
a high speed rotor revolving at speeds of
COOLANT
2000 to 18,000 rpm. OUTLET
COOLANT
The clearance between the rotor and the COOLANT
INLET
stator is adjustable, usually from 0.001
inch upward. The emulsion mixture,
while passing between the rotor and the OUTLET

9|P age
BWU/B. Pharm/III Semester / Pharmaceutical Engineering

stator, is subjected to a tremendous shearing action, which effects a fine dispersion of uniform size.
The shearing forces applied in the colloid mill usually raises the temperature within the emulsion.
Hence, a coolant is used to absorb the excess heat.
Advantage
(i) Very high shearing force can be generated.
(ii) Very fine particles can be prepared.
(iii)Particularly useful in preparing suspensions containing poorly wetted solids.
(iv) Useful for the preparation of relatively viscous emulsions.

Silverson emulsifier:
Principle: Silverson emulsifier produces high shear force and turbulence with the help of high
speed rotors. Due to the turbulence, the liquid pass through the fine interstices formed by closely
placed perforated metal sheets. The circulation of the material ensures the rapid breakdown of the
dispersed liquid into smaller globules.

Construction: It consists of long supporting columns connected to a motor providing support to

the head. The shaft is centrally placed with the motor connected in one end and the emulsifying
head in the other. The head contains turbine blades. The blades are surrounded by a mesh which is
further enclosed by a cover having perforations.
Working: The emulsifier head is dipped completely in a vessel containing immiscible liquids.
When the motor starts to rotate, the turbine blades fitted with central shaft also rotates at a high
speed. As a result of pressure difference, the liquids are sucked into the head from the center of the
base and subjected to intense mixing. Centrifugal force expel the content out of the head with a
great force through the mesh and onto the cover. This result the formation of a fine emulsion. The
circulation pattern ensures the breakdown of bigger globules into smaller globules.
Uses: It is used for the preparation of the emulsions and creams of fine particle size.
Advantages:
i) It is available in different sizes ranging from few millilitres to several thousand litres.
ii) It can be used for batch operations as well as continuous operation.

Disadvantages: There is a chance of clogging of the pores present in the mesh.

10 | P a g e