Mixing and Homogenization
Syllabus:
Theory of mixing, solid-solid, solid-liquid and
liquid-liquid mixing equipments, homogenizers.
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.
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 solids mixing proceeds by a combination of one or more of the following
mechanisms:
1. 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 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.
2. 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.
3. 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.
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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.
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Cubical and polyhedron shaped blenders with the
rotating axis set at various angles also are available.
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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.
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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.
MOA
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 Þ does not produce desired tumbling or
cascading motion nor does
it generate rapid shear rates.
·
If the rotation speed is too high Þ produce centrifugal force sufficient to hold
the powder to the sides
of the mixer and thereby reduce efficiency.
·
If the rotation speed is optimumÞ 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.
RIBBON BLENDER
Sigma blade and planetary mixers
Sigma blade and
planetary mixers are also used at a step prior to addition of liquid (e.g
just before wet massing in tablet wet-granulation). Fig. See semisolid mixers
for sigma blenders and
Conical orbital screw mixer (Nautamixer)
Conical orbital screw mixer consists of a conical vessel fitted at
the base with a rotating screw, which is fastened to the end of a rotating arm
at the upper end.
Working:
The mixer screw rotates at its
own axis and simultaneously moves in the orbit at the periphery of the conical
container. It 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.
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.
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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.
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.
·
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.
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 (h) of
the liquid.
i.e. v µ 1/h
D/d µ 1/h
·
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: upto
8000 rpm.
·
Propeller mixer is not normally effective with
liquids of viscosity greater than about 5 Ns/m2 ; which is some what
greater than glycerin or castor oil.
Vortexing
and its remedies:
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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)]
(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. 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 attached to the wall of the vessel. [fig (f)]
Use:
(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:
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(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 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.
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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 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 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 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 same time
the planet is rotating around the sun. The design of the blade is as shown in
the figure. There is very little clearance between the blade and the wall of the
container.
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.
(ii) Sigma Blender:
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Construction:
It uses two mixer blades, the
shape of which resembles the Greek letter “sigma” (S).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 material and divisions into two troughs, while the
blade shape and difference in speed causes end-to-end movement.
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. Roller mills consists of one or more rollers. Of
these three roll type is preferred for semisolid preparations. The rollers
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 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.
HOMOGENIZERS
The principle of homogenizers is
that large globules in a coarse emulsion are broken down into smaller globules
by passage under pressure througha narrow orifice.
Working principle:
The coarse emulsion (basic
product) enters the valve seat at high pressure (1000 to 5000 psi), flows
through the region between the valve and the seat at high velocity with a rapid
pressure drop, causing cavitation; subsequently the mixture hits the impact
ring causing further disruption and then is discharged as a homogenized
product. It is postulated that circulation and turbulence are responsible
mainly for the homogenization that takes place.
Sometimes a single homogenization
may produce an emulsion, which although its particle size is small, has a
tendency to clump of form clusters. Emulsions of this type exhibit increased
creaming tendencies. This is corrected by passing the emulsion through the
first stage of homogenization at a high pressure (e.g. 3000 to 5000 psi) and
then through the second stage at a greatly reduced pressure (e.g. 1000 psi).
This breaks down any clusters formed in the first step (it is a two stage
homogenizer).
Applications:
Homogenizers may be used in one
of two ways:
(i) The
ingredients in the emulsion are mixed and then passed through the homogenizer
to produce the final product.
(ii) A
coarse emulsion is prepared in some other way and then passed through a
homogenizer for the purpose of decreasing the particle size and obtaining a
greater degree of uniformity and stability.
COLLOID MILL
The principle of
operation of the colloid mill is the passage of the mixed phases of an emulsion
formula between a stator and a high speed rotor revolving at speeds of 2000 to
18,000 rpm.
The clearance between the rotor
and the stator is adjustable, usually from 0.001 inch upward. The emulsion
mixture, while passing between the rotor and the 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.