MIXIN
G
MIXIN
G
• Mixing may be definedas a unit operationthat tends
to
result in a randomization of dissimilar
particles within a system.
2
TYPES OF MIXTURES
• Positive mixtures - Positive mixtures are formed
from materials such as gases or miscible liquids
which mix spontaneously and irreversibly by
diffusion, and tend to approach a perfect mix.
• Negative mixtures- With negative mixtures
the components will tend to separate out. If this
occurs quickly, then energy must be continuously
input to keep the components adequately
dispersed, e.g. with a suspension formulation,
such as calamine lotion.
• Neutral mixtures - Neutral mixtures are said to be
static in behavior, i.e. the components have no
tendency to mix spontaneously or segregate
spontaneously once work has been input to mix
them. Examples of this type of mixture include
mixed powders, pastes and ointments
3
Application of
mixing
• Mixing is one of the most common pharmaceutical
operations. It is involved in preparation of many types of
formulations.
• Mixing of powders is done prior to filling in capsules,
sachets
and as dry powder inhalers.
• Blending of powders is required in the preparation of
talcum, tooth powders etc.
• Dry mixing of materials is required for direct
compression into
tablets.
• Mixing of miscible liquids is done to prepare linctuses
• Mixing of immiscible liquids is done to prepare
emulsions.
• Mixing is needed to prepare semi-solid dosage forms
such as
4
OBJECTIVES OF MIXING
• Simple physical Mixture: This may be simply
the production of a blend of two or more miscible
liquids or two or more uniformly divided solids.
• Physical Change: Mixing may aim at producing a
change that is physical as distinct from chemical, for
example the solution of a soluble substance.
• Dispersion: This includes the dispersion of two
immiscible liquids to form an emulsion or the
dispersion of a solid in a liquid to give a suspension or
paste.
• Promotion of Reaction: Mixing will usually
encourage (and control at the same time) a
chemical reaction, so ensuring uniform products.
5
Diff. between liquid and solid
mixing
Liquid Mixing Solid Mixing
Flow currents are responsible for
transporting unmixed material to
the mixing zone adjacent to
impeller
Flow currents are not possible
Truly homogenous liquid phase can
be observed
Product often consists of 2 or
more easily identifiable phases
Small sample size is sufficient to
study degree of mixing
Large sample size is required
Mixing requires low power Mixing requires high power
6
Types of
mixing
1. Solid-solid mixing
2. Liquid-liquid mixing
3. mixing of immiscible
liquids
4. Solid-liquid mixing
5. Semi solid mixing
7
Solid-solid
mixing
• This is the process in which two or more than two
solid substance are mixed in a mixer by continuous
movement of the particle.
• MECHANISM OF MIXING IN SOLIDS:
• convective mixing (macro mixing): In the case of
convective mixing material in the mixer is transported
from one location to another. Usually this type of
mixing is applied for free- flowing and coarse materials
• Shear mixing: Force of attraction are broken down so
that each particles moves on its own between region of
different composition.
• Diffusive mixing (micro mixing): Random motion of
particles within the powder bed thereby particle change
their position relative to one another
8
Degree of
mixing
• The mixedness or goodness of mixing of the
powder system is important because mixing
involves particles with different properties and
different ratios.
• A powder mixture can be visualized as shown in
the
slide.
9
IDEAL MIXING OR PERFECT MIXING
• Ideal degree of mixing is represented by a
chessboard with black and white squares
representing two components (equal quantities).
• It indicates that each particle of one component is
lying adjacent to a particle of another component.
• Such an arrangement is practically impossible to
achieve in any mixer.
• A random mixture is the one in which probability of
finding the particle of one component at any point
is equal to the proportion of that component in the
mixture
10
Factors affecting powder
mixing
• Particle size: It is easy to mix materials having the
same particle sizes. If there is variation in
particle sizes, separation may occur since the
small particles move downward through the
spaces between the bigger particles. As the
particle size increases, flow properties of the material
increases which facilitates mixing.
• Particle shape: Particles should be spherical in
shape for uniform mixing. If there is irregular
shape of the particles in a material, then they
become interconnected in such a way that their
separation is relatively difficult after mixing than if
the particle shape is regular.
12
Factors affecting powder
mixing
• Particle charge: If the particle has
some electrostatic charge that cause
attraction forces between particles, then
there are more chances of segregation or
separation.
• Nature of the particle: Particle
hardness, elasticity, porosity, texture are also
the factors that affect mixing phenomena
greatly.
• Relative Density: For uniform mixing,
the particles of the materials to be mixed
should have the same density
approximately. If the components are of
different density, the denser material will
sink through the lighter one and demixing
13
Factors affecting powder
mixing
• Proportion of materials: It is easy to
mix materials which are equal in proportion by
weight or volume (1:1). If there is a large
difference in the proportion of materials, then
mixing is done in the ascending order of their
weights.
• Presence of Moisture: Moisture present
in particles heap also affects mixing
phenomena. For example mixing of dry clay is
more rapid and efficient than wet mixing of
clay. In fact proper mixing requires specific
moisture content in bulk.
14
Classification of
mixers
15
Classificatio
n of
Mixers
Free
Flowing
Solids
V Cone
Blende
r
Double
Cone
Blender
Cohesive
Solids
Planetar
y
Mixer
Sigma
Blende
r
16
Classification
of Mixers
Batch
Mixer
Double
Cone
Blender
Twin Shell
Blender
Ribbon
Blender Sigma
Blender
Planetary
Mixer
Continuous
Mixer
Barrel
Mixer
Zig-Zag
Mixer
Cylindrical
blenders
17
Cylindrical
blenders
• Tumblers or cylindrical blenders with no mixing blade
are meant for dry powders
• Equipment consists of a container of any geometric
form. Container is mounted on special roller so that
it can be rotated about any axis.
18
DOUBLE CONE
BLENDER:
• Principle: It consists of double cone mounted on
a rotating shaft.
• As the mixer rotates, the materials to be mixed
undergo a tumbling motion.
• Mixing takes place due to convective transport
and diffusion.
19
20
Double Cone
Blender
• Construction: It consists of a container
in the shape of a double cone
mounted on a rotating shaft.
• Material loading 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.
• The rate of rotation commonly ranges
from 30 -100 rpm.
21
Double Cone
Blender
• Working: The material
to
loaded approximately two-
third
be mixed is
of the
volume of the blender.
• The blender is allowed to rotate.
• The materials inside the mixer
undergo a tumbling motion.
• The particles of the materials are
displaced from one location to
another to enable mixing to occur
by convection and diffusion.
22
Double Cone
Blender
Uses:
• The mixer is good for mixing of free-
flowing granules/powders but
poor for cohesive/poorly flowing
powders because the shear forces
generated are usually insufficient
to break up any aggregates.
• A common use
is
lubricants,
glidants
in the
blending of or
disintegrants
wit
h
granules prior to
tableting.
23
Double Cone
Blender
Merits:
• The mixer is suitable for mixing of fragile
granules as there is minimum attrition
• It is available in large capacity
• It is easy to clean, load and unload
• It is easy to maintain
Demerits:
• It requires a high headspace for installation
• It is suitable only for mixing of free flowing and
granular materials
• It is not suitable for mixing of powders with
large differences in particle size distribution
because not enough shear is applied to the
materials.
24
V Cone
Blender
25
V-cone
blender
• It is V shaped and made up of stainless steel
or transparent plastic. Material is loaded through
either of shell hatches and emptying is normally
done through an apex port.
• The material is loaded approximately 50-60 % of the
total volume.
• Small models – 20 kg , rotate at 35 rpm Large models
– 1 ton, rotate at 15 rpm.
• 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
26
Advantages and
Disadvantages
Advantages of V cone blender
• If fragile granules are to be blended, twin shell
blender is suitable because of minimum attrition.
• They handle large capacities.
• Easy to clean , load, and unload.
• This equipment requires minimum maintenance.
Disadvantages of V cone blender
• Twin shell blender needs high headspace for
installation.
• It is not suitable for fine particulate system or
ingredients of large differences in the particle
size distribution, because not enough shear is
applied.
• If powders are free flowing, serial dilution is
27
DOUBLE CONE AND TWIN SHELL
BLENDER WITH AGITATION MIXING BLADE
28
DOUBLE CONE AND TWIN SHELL BLENDER
WITH AGITATION MIXING BLADE
• The double cone and v-cone blender
can be fitted with mixing blades for
agitation.
• These blenders are same as double
cone and v-cone blender in terms of
construction and working with the
added advantage of the presence of
agitator blade in them.
• Uses: These blenders are suitable
for mixing of not only dry
powders/granules but also for mixing
29
DOUBLE CONE AND TWIN SHELL BLENDER WITH
AGITATION MIXING BLADE
• Merits:
• Attachments of agitator blades
are beneficial for both wet and dry
mixing.
• Wide range of shearing force can
be applied with agitator bars
permitting the intimate mixing of
very fine as well as coarse powders.
• Serial dilution is not needed
when incorporating low-dose active
30
• Demerits:
• Attrition is large, size reduction of
friable particles results.
• Cleaning may be a problem,
because agitator assembly must be
removed and the packing should
be replaced for a product change
over.
• Potential packing (sealing) problems
may occur in these mixers.
31
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
32
Ribbo
n
33
Ribbon
Mixer
34
Ribbon Blender
Construction: It consists of
horizontal cylindrical trough usually
open at the top and fitted with helical
blades.
• The blades are mounted on a
shaft through the long axis of the tank
and are often of both right and left-hand
twist.
• The blades are connected to fixed
speed drive.
•
35
Ribbon Blender
• Working: During mixing the blades rotate at
fixed speeds.
• One blade moves the solids slowly in
one direction.
• At the same time the other blade quickly
turns the solids in opposite direction.
• The powders are lifted and allowed to cascade
to the bottom of the container with a
centrally located screw.
• After blending, the blend is discharged
from a discharge valve located at the
bottom of the trough.
36
Ribbon
Mixer
37
Ribbon
Mixer
• For mixing finely divided solids, wet solid mass,
sticky & plastic solids. It is used for liquid-solid & solid-
solid mixing
Advantages:
• High shear can be applied by using baffles, which
bring about a rubbing & break down aggregates.
Disadvantages:
• Shearing action is less than in planetary mixer.
• Dead spots are observed
• It is a poor mixer, because movement of particles is
2 –
dimensional
• Speed is fixed
38
Sigma Blade
Mixer
39
Sigma Blade
Mixer
• Principle: This robust mixer will deal
with stiff pastes and ointments and
depends for its action on the close
intermeshing of the two blades
which resemble the Greek
letter Ʃ in shape.
• The clearance between the blades and
the mixing trough is kept small by the
shape.
• Inter meshing of sigma blades creates
high shear and kneading action.
40
Sigma Blade
Mixer
Construction: It consists of double
trough shaped stationary bowl.
Two sigma shaped blades are
fitted horizontally in each trough of the
bowl.
These blades are connected to a fixed
speed drive.
Mixer is loaded from top and unloaded
by tilting the entire bowl.
41
Sigma Blade
Mixer
• Working: Powders are introduced from the top
of the trough.
• During blending, the two blades rotate at
different speeds, one usually about twice the
speed of 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 trough resulting in cascading action.
• The perforated blades helps to break lumps
and aggregates creating high shear forces.
• The final stage of mix represents an
equilibrium state.
42
Sigma blade
mixer
43
Sigma Blade
Mixer
Uses: The mixer is used in the
wet granulation process in the
manufacture of tablets, pill masses and
ointments.
It is primarily used for liquid – solid
mixing, although it can be used for
solid – solid mixing.
It is ideal for mixing, kneading of
highly viscous mass, sticky and
dough like products.
44
Sigma Blade
Mixer
• Merits:
• Sigma blade mixer creates a
minimum dead space during
mixing.
• It has close tolerances between the
blades and the sidewalls as well as
bottom of the mixer shell.
• Demerits:
• Sigma blade mixer works at a fixed
speed.
45
Planetary
mixer
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.
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 it
is normally built with variable speed drive.
46
47
• Working: The mixing blade is set off centre and is
carried on a rotating arm.
• It therefore travels round the circumference of the
rotating bowl while simultaneously rotating around its
axis.
• is therefore a double rotation similar to that of a
spinning planet around the sun-hence the name.
• The blade tears the mass apart and shear is applied
between the moving blade and its stationary wall.
• The plates in the blade are sloped so that the powder
makes an upward movement.
• Thus the tumbling motion is also achieved.
• Since the speed of the blade can be changed, initially
the blade is allowed to move at slow speed for pre-
mixing and finally at increased speed for active
mixing.
• The mixer is designed so that the blade covers all the
volume of the mixer.
48
• Uses: Planetary mixer is a very efficient mixer and can
break down agglomerates rapidly producing precise
blends. Low speeds are used for dry blending and fast
for wet granulation.
• Merits:
• In this mixer, the speed of rotation can be varied at
will. It is more useful for wet granulation process as
compared to sigma blade and ribbon blender.
• Demerits:
• Mechanical heat is buildup within the powder mix.
• It requires high power.
• It has limited size and is useful for batch work only.
49
Planetary
Mixer
50
MIXING OF MISCIBLE LIQUID
AND SUSPENSION
• Mobile liquids with a low viscosity are
easily mixed with each other.
• Similarly, solid particles are
readily suspended in mobile liquids,
although the particles are likely to
settle rapidly when mixing is
discontinued.
• Viscous liquids are more difficult to stir
and mix, but they reduce the
sedimentation rate of suspended
51
LIQUID
MIXING
• The mechanism of mixing can be classified into
four classes .
• Bulk transport
• Turbulent
• Laminar mixing
• Molecular diffusion
52
Mechanism of mixing in
liquids
• Bulk Transport: Bulk transport involves the movement
of a relatively large amount of material from one
position in the mixing equipment to another.
• Turbulent Mixing: Turbulent mixing arises from
the haphazard movement of molecules when forced
to move in a turbulent manner. The constant changes
in speed and direction of movement means that
induced turbulence is a highly effective mechanism for
mixing.
• Laminar Mixing: It is the mixing of two dissimilar
liquids through laminar flow, i.e., the applied shear
stretches the interphase between them. In this
mechanism, layers fold back upon themselves.
• Molecular Diffusion: It is the mixing at molecular level
in which molecules diffuse due to thermal motion.
53
FACTORS INFLUENCING LIQUID MIXING
• Viscosity: Mixing is affected by viscosity of
the liquids. More the viscosity of the liquids
more will be the difficult to proper mixing.
• Miscibility of the liquids: It is easier to mix
a mixture of miscible liquids than immiscible
ones.
• Surface tension of liquids: surface tension
of liquid is also an important factor that effects
mixing. High surface tension reduces extent of
mixing.
• Temperature: Temperature also affects mixing
as viscosity changes with the change in
54
FACTORS INFLUENCING LIQUID MIXING
• Mixer volume: Mixer volume also
affects mixing phenomena.
Mixer volume should be such that
over filling should not be done as it
decreases efficiency of mixing and
mostly material can’t be mixed
thoroughly.
• Mixing
time:
important
for
mixing timeis also
very proper
mixing. There is
always an optimum mixing time for
specific conditions in which mixing is
taken place.
55
Mixing equipment
• A system for batch mixing
commonly consists of two
primary components:
 A tank or other container suitable to
hold the material being mixed and
 A means of supplying energy to the
system so as to bring about rapid
mixing.
56
57
Mixing
equipment
• The mixing device is called impeller,
which is mounted with the help of
shaft. The shaft is driven by a motor.
• Three
main
namely-
• Propeller
• Turbine
and
• Paddles
types of impeller are
used
58
Flow pattern during mixing
• The movement of the liquid at any point in the vessel
will have three velocity components which are as
follows:
• Radial component, acting in a direction vertical to
the impeller shaft. Excessive radial movement
will take materials to the container wall, whence
they fall to the bottom and may rotate as a mass
beneath the impeller.
59
Flow pattern during
mixing
• A longitudinal or axial component acting parallel to
the impeller shaft. Adequate longitudinal pattern is
best used to generate strong vertical currents
particularly when suspending solids are present in a
liquid.
60
Flow pattern during
mixing
• A tangential component acting in a direction
that is tangent to the circle of rotation round
the impeller shaft.
61
Flow pattern during mixing
62
Mixing
devices
63
Propellers
64
Propeller
s
• It consists of number of blades,
generally 3 bladed design is most
common for liquids.
• Blades may be right or left
handed depending upon the slant of
their blades.
• Two or more propellers are used for
deep tank.
• Size of propeller is small and
may increased up to 0.5 metres
depending upon the size of the tank.
•
65
Propeller
s
Uses:
The propeller will perform most
mixing duties with liquids when used
correctly.
It is the best unit when strong
vertical currents are required as in
suspension of solids in a liquid.
It is not normally suitable when
considerable shear is needed as in
emulsification.
66
Propeller
s
Merits:
• Used when high mixing capacity is required.
• Effective for liquids which have maximum
viscosity of 2.0 pascals. sec or slurry up to 10%
solids of fine mesh size.
• Effective gas-liquid dispersion is possible
at laboratory scale.
Demerits:
• Propellers are not normally effective with
liquids of viscosity greater than 5
pascal.second, such as glycerin castor oil, etc.,
67
68
Propeller Mixing Process
Turbine
s
•
A turbine mixer may be used for
more viscous liquids.
•A turbine consists of a circular disc
to which a number of short vertical
blades are attached.
•Blades may be straight or curved.
•The diameter of the turbine ranges
from 30-50% of the diameter of the
vessel.
•The turbines impeller is rotated at a
lower speed than the propellers (50-
200rpm).
69
70
Flat blade
turbine
Pitched blade
turbine
71
Most turbine impellers have flat blades
and cause the liquid to move rapidly in
a radial direction.
turbine
s
Uses:
 Turbine mixers are satisfactory
with mobile liquids, but, because
of the greater shearing effects they
can deal with more viscous
liquids than the propeller mixers.
 The turbines are particularly
suitable for preparing emulsions.
72
Turbine
s
73
Turbine
Turbines
Merits:
• Turbines give greater shearing forces than propellers
and is suitable for emulsification.
• Effective for high viscous solutions.
• They can handle slurries with 60% solids.
• Turbines are suitable for liquids of large volume and
high viscosity, if the tank is baffled.
Demerits:
• The standard turbine mixer is less suitable than
propellers for suspending heavy solids because of
absence of vertical flow.
74
Paddle
s
• 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 dished or hemispherical in shape and
have a large surface area in relation to the
tank in which they are used.
• Paddles rotates at a low speed of 100 rpm.
• They push the liquid radially and tangentially
• In deep tanks several paddles are attached
one above the other on the same shaft.
75
76
Hemispherical Paddle
Flat Blade Paddle
Paddle
s
Uses: Paddles are used in the
manufacture of antacid suspensions,
antidiarrheal mixtures such as
bismuth-kaolin.
Merits:

Vortex
paddl
e
mixin
g.
formation is not
possible with impellers
because of low speed
Demerits:
 Mixing of the suspension is poor
therefore baffled tanks are required.
77
Vortex
formation
• A strong circulatory flow pattern
sometimes manifests into formation
of a vortex near the impeller shaft .
78
VORTEX FORMATION
Vortex can be formed when:
 Shaft is placed symmetrically in the
tank. Blades in the turbines are
arranged perpendicular to the central
shaft.
At high impeller speeds
 In unbaffled Containers
79
Vortex formation reduces mixing intensity by reducing
velocity of the impeller relative to the surrounding
fluid
80
Prevention of Vortex Formation
Off-Centre Inclined Side-entry Push-pull
Baffled Container
Mixing of immiscible
Liquids
Mixing of immiscible liquids is carried
in pharmacy mainly in the
manufacturing of emulsions.
The
equipment
emulsion
is
used
calle
d
for preparing
the
emulsifier
or
homogenizer.
Silverson mixer, colloid mill and
rapisonic homogenizers are
suitable for emulsification.
81
82
SILVERSON MIXER-HOMOGENIZER
Silverson Mixer-Emulsifier
Principle:
• It produces intense shearing forces
and turbulence by use of high speed rotors.
• The emulsifier head is dipped in the mixture
of immiscible liquids.
• The liquid mixture is sucked inside
the emulsifying head due to suction and is
dispersed in the form of fine globules when
acted upon by the turbine blade and
issued through the perforations from the
head.
83
SILVERSON HOMOGENIZER
CONSTRUCTION:
• It consists of long supporting columns and a
central portion.
• The central portion consists of a shaft which is
connected
to motor at one end and other to the emulsifying
head.
• The emulsifying head carries turbine blades.
• The blades are surroundedby a mesh, which is
further enclosed by a cover having openings.
84
SILVERSON HOMOGENIZER
• 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 blade at a very high speed. This
creates a pressure difference. As a result, liquids are
sucked into the emulsifier head from the center of the
base and subjected to intense mixing action.
Centrifugal force 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 ones.
85
Silverson mixer -
Emulsifier
 Uses: Used for the preparation of emulsions and
creams of fine particle size.
 Advantages: Silverson mixer is available in different
sizes to handle the liquids ranging from a few
milliliters to several thousand liters.
• Can be used for batch operations as well as
for continuous operations by incorporating into a
pipeline, through which the immiscible liquids flow.
 Disadvantages: Occasionally, there is a chance
is clogging of pores of the mesh
86
Silverson
Emulsifier
87
Semi-Solid
Mixing
• 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 following mixers are helpful for mixing:
• Agitator mixers: e.g.:- Sigma mixers and Planetary
mixer.
• Shear mixers: e.g.:- Triple roller mill and Colloidal mill.
88
Mixing of semi-
solids
• 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. Material that finds its way to 'dead'
spots will remain there. 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, as diffusion and convection cannot occur.
The forces required for efficient mixing are high and
consumption of power is also high. Hence the
equipment must be rugged
constructed to
exhibit
dilatant
tolerate
propert
y
these forces. Some
semisolids 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.
89
Colloid
Mill
90
Triple Roller
Mill
91

mixing-..pptx pharmaceutical engineering

  • 1.
  • 2.
    MIXIN G • Mixing maybe definedas a unit operationthat tends to result in a randomization of dissimilar particles within a system. 2
  • 3.
    TYPES OF MIXTURES •Positive mixtures - Positive mixtures are formed from materials such as gases or miscible liquids which mix spontaneously and irreversibly by diffusion, and tend to approach a perfect mix. • Negative mixtures- With negative mixtures the components will tend to separate out. If this occurs quickly, then energy must be continuously input to keep the components adequately dispersed, e.g. with a suspension formulation, such as calamine lotion. • Neutral mixtures - Neutral mixtures are said to be static in behavior, i.e. the components have no tendency to mix spontaneously or segregate spontaneously once work has been input to mix them. Examples of this type of mixture include mixed powders, pastes and ointments 3
  • 4.
    Application of mixing • Mixingis one of the most common pharmaceutical operations. It is involved in preparation of many types of formulations. • Mixing of powders is done prior to filling in capsules, sachets and as dry powder inhalers. • Blending of powders is required in the preparation of talcum, tooth powders etc. • Dry mixing of materials is required for direct compression into tablets. • Mixing of miscible liquids is done to prepare linctuses • Mixing of immiscible liquids is done to prepare emulsions. • Mixing is needed to prepare semi-solid dosage forms such as 4
  • 5.
    OBJECTIVES OF MIXING •Simple physical Mixture: This may be simply the production of a blend of two or more miscible liquids or two or more uniformly divided solids. • Physical Change: Mixing may aim at producing a change that is physical as distinct from chemical, for example the solution of a soluble substance. • Dispersion: This includes the dispersion of two immiscible liquids to form an emulsion or the dispersion of a solid in a liquid to give a suspension or paste. • Promotion of Reaction: Mixing will usually encourage (and control at the same time) a chemical reaction, so ensuring uniform products. 5
  • 6.
    Diff. between liquidand solid mixing Liquid Mixing Solid Mixing Flow currents are responsible for transporting unmixed material to the mixing zone adjacent to impeller Flow currents are not possible Truly homogenous liquid phase can be observed Product often consists of 2 or more easily identifiable phases Small sample size is sufficient to study degree of mixing Large sample size is required Mixing requires low power Mixing requires high power 6
  • 7.
    Types of mixing 1. Solid-solidmixing 2. Liquid-liquid mixing 3. mixing of immiscible liquids 4. Solid-liquid mixing 5. Semi solid mixing 7
  • 8.
    Solid-solid mixing • This isthe process in which two or more than two solid substance are mixed in a mixer by continuous movement of the particle. • MECHANISM OF MIXING IN SOLIDS: • convective mixing (macro mixing): In the case of convective mixing material in the mixer is transported from one location to another. Usually this type of mixing is applied for free- flowing and coarse materials • Shear mixing: Force of attraction are broken down so that each particles moves on its own between region of different composition. • Diffusive mixing (micro mixing): Random motion of particles within the powder bed thereby particle change their position relative to one another 8
  • 9.
    Degree of mixing • Themixedness or goodness of mixing of the powder system is important because mixing involves particles with different properties and different ratios. • A powder mixture can be visualized as shown in the slide. 9
  • 10.
    IDEAL MIXING ORPERFECT MIXING • Ideal degree of mixing is represented by a chessboard with black and white squares representing two components (equal quantities). • It indicates that each particle of one component is lying adjacent to a particle of another component. • Such an arrangement is practically impossible to achieve in any mixer. • A random mixture is the one in which probability of finding the particle of one component at any point is equal to the proportion of that component in the mixture 10
  • 11.
    Factors affecting powder mixing •Particle size: It is easy to mix materials having the same particle sizes. If there is variation in particle sizes, separation may occur since the small particles move downward through the spaces between the bigger particles. As the particle size increases, flow properties of the material increases which facilitates mixing. • Particle shape: Particles should be spherical in shape for uniform mixing. If there is irregular shape of the particles in a material, then they become interconnected in such a way that their separation is relatively difficult after mixing than if the particle shape is regular. 12
  • 12.
    Factors affecting powder mixing •Particle charge: If the particle has some electrostatic charge that cause attraction forces between particles, then there are more chances of segregation or separation. • Nature of the particle: Particle hardness, elasticity, porosity, texture are also the factors that affect mixing phenomena greatly. • Relative Density: For uniform mixing, the particles of the materials to be mixed should have the same density approximately. If the components are of different density, the denser material will sink through the lighter one and demixing 13
  • 13.
    Factors affecting powder mixing •Proportion of materials: It is easy to mix materials which are equal in proportion by weight or volume (1:1). If there is a large difference in the proportion of materials, then mixing is done in the ascending order of their weights. • Presence of Moisture: Moisture present in particles heap also affects mixing phenomena. For example mixing of dry clay is more rapid and efficient than wet mixing of clay. In fact proper mixing requires specific moisture content in bulk. 14
  • 14.
    Classification of mixers 15 Classificatio n of Mixers Free Flowing Solids VCone Blende r Double Cone Blender Cohesive Solids Planetar y Mixer Sigma Blende r
  • 15.
    16 Classification of Mixers Batch Mixer Double Cone Blender Twin Shell Blender Ribbon BlenderSigma Blender Planetary Mixer Continuous Mixer Barrel Mixer Zig-Zag Mixer
  • 16.
  • 17.
    Cylindrical blenders • Tumblers orcylindrical blenders with no mixing blade are meant for dry powders • Equipment consists of a container of any geometric form. Container is mounted on special roller so that it can be rotated about any axis. 18
  • 18.
    DOUBLE CONE BLENDER: • Principle:It consists of double cone mounted on a rotating shaft. • As the mixer rotates, the materials to be mixed undergo a tumbling motion. • Mixing takes place due to convective transport and diffusion. 19
  • 19.
  • 20.
    Double Cone Blender • Construction:It consists of a container in the shape of a double cone mounted on a rotating shaft. • Material loading 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. • The rate of rotation commonly ranges from 30 -100 rpm. 21
  • 21.
    Double Cone Blender • Working:The material to loaded approximately two- third be mixed is of the volume of the blender. • The blender is allowed to rotate. • The materials inside the mixer undergo a tumbling motion. • The particles of the materials are displaced from one location to another to enable mixing to occur by convection and diffusion. 22
  • 22.
    Double Cone Blender Uses: • Themixer is good for mixing of free- flowing granules/powders but poor for cohesive/poorly flowing powders because the shear forces generated are usually insufficient to break up any aggregates. • A common use is lubricants, glidants in the blending of or disintegrants wit h granules prior to tableting. 23
  • 23.
    Double Cone Blender Merits: • Themixer is suitable for mixing of fragile granules as there is minimum attrition • It is available in large capacity • It is easy to clean, load and unload • It is easy to maintain Demerits: • It requires a high headspace for installation • It is suitable only for mixing of free flowing and granular materials • It is not suitable for mixing of powders with large differences in particle size distribution because not enough shear is applied to the materials. 24
  • 24.
  • 25.
    V-cone blender • It isV shaped and made up of stainless steel or transparent plastic. Material is loaded through either of shell hatches and emptying is normally done through an apex port. • The material is loaded approximately 50-60 % of the total volume. • Small models – 20 kg , rotate at 35 rpm Large models – 1 ton, rotate at 15 rpm. • 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 26
  • 26.
    Advantages and Disadvantages Advantages ofV cone blender • If fragile granules are to be blended, twin shell blender is suitable because of minimum attrition. • They handle large capacities. • Easy to clean , load, and unload. • This equipment requires minimum maintenance. Disadvantages of V cone blender • Twin shell blender needs high headspace for installation. • It is not suitable for fine particulate system or ingredients of large differences in the particle size distribution, because not enough shear is applied. • If powders are free flowing, serial dilution is 27
  • 27.
    DOUBLE CONE ANDTWIN SHELL BLENDER WITH AGITATION MIXING BLADE 28
  • 28.
    DOUBLE CONE ANDTWIN SHELL BLENDER WITH AGITATION MIXING BLADE • The double cone and v-cone blender can be fitted with mixing blades for agitation. • These blenders are same as double cone and v-cone blender in terms of construction and working with the added advantage of the presence of agitator blade in them. • Uses: These blenders are suitable for mixing of not only dry powders/granules but also for mixing 29
  • 29.
    DOUBLE CONE ANDTWIN SHELL BLENDER WITH AGITATION MIXING BLADE • Merits: • Attachments of agitator blades are beneficial for both wet and dry mixing. • Wide range of shearing force can be applied with agitator bars permitting the intimate mixing of very fine as well as coarse powders. • Serial dilution is not needed when incorporating low-dose active 30
  • 30.
    • Demerits: • Attritionis large, size reduction of friable particles results. • Cleaning may be a problem, because agitator assembly must be removed and the packing should be replaced for a product change over. • Potential packing (sealing) problems may occur in these mixers. 31
  • 31.
    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 32
  • 32.
  • 33.
  • 34.
    Ribbon Blender Construction: Itconsists of horizontal cylindrical trough usually open at the top and fitted with helical blades. • The blades are mounted on a shaft through the long axis of the tank and are often of both right and left-hand twist. • The blades are connected to fixed speed drive. • 35
  • 35.
    Ribbon Blender • Working:During mixing the blades rotate at fixed speeds. • One blade moves the solids slowly in one direction. • At the same time the other blade quickly turns the solids in opposite direction. • The powders are lifted and allowed to cascade to the bottom of the container with a centrally located screw. • After blending, the blend is discharged from a discharge valve located at the bottom of the trough. 36
  • 36.
  • 37.
    Ribbon Mixer • For mixingfinely divided solids, wet solid mass, sticky & plastic solids. It is used for liquid-solid & solid- solid mixing Advantages: • High shear can be applied by using baffles, which bring about a rubbing & break down aggregates. Disadvantages: • Shearing action is less than in planetary mixer. • Dead spots are observed • It is a poor mixer, because movement of particles is 2 – dimensional • Speed is fixed 38
  • 38.
  • 39.
    Sigma Blade Mixer • Principle:This robust mixer will deal with stiff pastes and ointments and depends for its action on the close intermeshing of the two blades which resemble the Greek letter Ʃ in shape. • The clearance between the blades and the mixing trough is kept small by the shape. • Inter meshing of sigma blades creates high shear and kneading action. 40
  • 40.
    Sigma Blade Mixer Construction: Itconsists of double trough shaped stationary bowl. Two sigma shaped blades are fitted horizontally in each trough of the bowl. These blades are connected to a fixed speed drive. Mixer is loaded from top and unloaded by tilting the entire bowl. 41
  • 41.
    Sigma Blade Mixer • Working:Powders are introduced from the top of the trough. • During blending, the two blades rotate at different speeds, one usually about twice the speed of 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 trough resulting in cascading action. • The perforated blades helps to break lumps and aggregates creating high shear forces. • The final stage of mix represents an equilibrium state. 42
  • 42.
  • 43.
    Sigma Blade Mixer Uses: Themixer is used in the wet granulation process in the manufacture of tablets, pill masses and ointments. It is primarily used for liquid – solid mixing, although it can be used for solid – solid mixing. It is ideal for mixing, kneading of highly viscous mass, sticky and dough like products. 44
  • 44.
    Sigma Blade Mixer • Merits: •Sigma blade mixer creates a minimum dead space during mixing. • It has close tolerances between the blades and the sidewalls as well as bottom of the mixer shell. • Demerits: • Sigma blade mixer works at a fixed speed. 45
  • 45.
    Planetary mixer Principle • Mechanism ofmixing 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. 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 it is normally built with variable speed drive. 46
  • 46.
  • 47.
    • Working: Themixing blade is set off centre and is carried on a rotating arm. • It therefore travels round the circumference of the rotating bowl while simultaneously rotating around its axis. • is therefore a double rotation similar to that of a spinning planet around the sun-hence the name. • The blade tears the mass apart and shear is applied between the moving blade and its stationary wall. • The plates in the blade are sloped so that the powder makes an upward movement. • Thus the tumbling motion is also achieved. • Since the speed of the blade can be changed, initially the blade is allowed to move at slow speed for pre- mixing and finally at increased speed for active mixing. • The mixer is designed so that the blade covers all the volume of the mixer. 48
  • 48.
    • Uses: Planetarymixer is a very efficient mixer and can break down agglomerates rapidly producing precise blends. Low speeds are used for dry blending and fast for wet granulation. • Merits: • In this mixer, the speed of rotation can be varied at will. It is more useful for wet granulation process as compared to sigma blade and ribbon blender. • Demerits: • Mechanical heat is buildup within the powder mix. • It requires high power. • It has limited size and is useful for batch work only. 49
  • 49.
  • 50.
    MIXING OF MISCIBLELIQUID AND SUSPENSION • Mobile liquids with a low viscosity are easily mixed with each other. • Similarly, solid particles are readily suspended in mobile liquids, although the particles are likely to settle rapidly when mixing is discontinued. • Viscous liquids are more difficult to stir and mix, but they reduce the sedimentation rate of suspended 51
  • 51.
    LIQUID MIXING • The mechanismof mixing can be classified into four classes . • Bulk transport • Turbulent • Laminar mixing • Molecular diffusion 52
  • 52.
    Mechanism of mixingin liquids • Bulk Transport: Bulk transport involves the movement of a relatively large amount of material from one position in the mixing equipment to another. • Turbulent Mixing: Turbulent mixing arises from the haphazard movement of molecules when forced to move in a turbulent manner. The constant changes in speed and direction of movement means that induced turbulence is a highly effective mechanism for mixing. • Laminar Mixing: It is the mixing of two dissimilar liquids through laminar flow, i.e., the applied shear stretches the interphase between them. In this mechanism, layers fold back upon themselves. • Molecular Diffusion: It is the mixing at molecular level in which molecules diffuse due to thermal motion. 53
  • 53.
    FACTORS INFLUENCING LIQUIDMIXING • Viscosity: Mixing is affected by viscosity of the liquids. More the viscosity of the liquids more will be the difficult to proper mixing. • Miscibility of the liquids: It is easier to mix a mixture of miscible liquids than immiscible ones. • Surface tension of liquids: surface tension of liquid is also an important factor that effects mixing. High surface tension reduces extent of mixing. • Temperature: Temperature also affects mixing as viscosity changes with the change in 54
  • 54.
    FACTORS INFLUENCING LIQUIDMIXING • Mixer volume: Mixer volume also affects mixing phenomena. Mixer volume should be such that over filling should not be done as it decreases efficiency of mixing and mostly material can’t be mixed thoroughly. • Mixing time: important for mixing timeis also very proper mixing. There is always an optimum mixing time for specific conditions in which mixing is taken place. 55
  • 55.
    Mixing equipment • Asystem for batch mixing commonly consists of two primary components:  A tank or other container suitable to hold the material being mixed and  A means of supplying energy to the system so as to bring about rapid mixing. 56
  • 56.
  • 57.
    Mixing equipment • The mixingdevice is called impeller, which is mounted with the help of shaft. The shaft is driven by a motor. • Three main namely- • Propeller • Turbine and • Paddles types of impeller are used 58
  • 58.
    Flow pattern duringmixing • The movement of the liquid at any point in the vessel will have three velocity components which are as follows: • Radial component, acting in a direction vertical to the impeller shaft. Excessive radial movement will take materials to the container wall, whence they fall to the bottom and may rotate as a mass beneath the impeller. 59
  • 59.
    Flow pattern during mixing •A longitudinal or axial component acting parallel to the impeller shaft. Adequate longitudinal pattern is best used to generate strong vertical currents particularly when suspending solids are present in a liquid. 60
  • 60.
    Flow pattern during mixing •A tangential component acting in a direction that is tangent to the circle of rotation round the impeller shaft. 61
  • 61.
  • 62.
  • 63.
  • 64.
    Propeller s • It consistsof number of blades, generally 3 bladed design is most common for liquids. • Blades may be right or left handed depending upon the slant of their blades. • Two or more propellers are used for deep tank. • Size of propeller is small and may increased up to 0.5 metres depending upon the size of the tank. • 65
  • 65.
    Propeller s Uses: The propeller willperform most mixing duties with liquids when used correctly. It is the best unit when strong vertical currents are required as in suspension of solids in a liquid. It is not normally suitable when considerable shear is needed as in emulsification. 66
  • 66.
    Propeller s Merits: • Used whenhigh mixing capacity is required. • Effective for liquids which have maximum viscosity of 2.0 pascals. sec or slurry up to 10% solids of fine mesh size. • Effective gas-liquid dispersion is possible at laboratory scale. Demerits: • Propellers are not normally effective with liquids of viscosity greater than 5 pascal.second, such as glycerin castor oil, etc., 67
  • 67.
  • 68.
    Turbine s • A turbine mixermay be used for more viscous liquids. •A turbine consists of a circular disc to which a number of short vertical blades are attached. •Blades may be straight or curved. •The diameter of the turbine ranges from 30-50% of the diameter of the vessel. •The turbines impeller is rotated at a lower speed than the propellers (50- 200rpm). 69
  • 69.
  • 70.
    Flat blade turbine Pitched blade turbine 71 Mostturbine impellers have flat blades and cause the liquid to move rapidly in a radial direction.
  • 71.
    turbine s Uses:  Turbine mixersare satisfactory with mobile liquids, but, because of the greater shearing effects they can deal with more viscous liquids than the propeller mixers.  The turbines are particularly suitable for preparing emulsions. 72
  • 72.
  • 73.
    Turbines Merits: • Turbines givegreater shearing forces than propellers and is suitable for emulsification. • Effective for high viscous solutions. • They can handle slurries with 60% solids. • Turbines are suitable for liquids of large volume and high viscosity, if the tank is baffled. Demerits: • The standard turbine mixer is less suitable than propellers for suspending heavy solids because of absence of vertical flow. 74
  • 74.
    Paddle s • A paddleconsists 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 dished or hemispherical in shape and have a large surface area in relation to the tank in which they are used. • Paddles rotates at a low speed of 100 rpm. • They push the liquid radially and tangentially • In deep tanks several paddles are attached one above the other on the same shaft. 75
  • 75.
  • 76.
    Paddle s Uses: Paddles areused in the manufacture of antacid suspensions, antidiarrheal mixtures such as bismuth-kaolin. Merits:  Vortex paddl e mixin g. formation is not possible with impellers because of low speed Demerits:  Mixing of the suspension is poor therefore baffled tanks are required. 77
  • 77.
    Vortex formation • A strongcirculatory flow pattern sometimes manifests into formation of a vortex near the impeller shaft . 78
  • 78.
    VORTEX FORMATION Vortex canbe formed when:  Shaft is placed symmetrically in the tank. Blades in the turbines are arranged perpendicular to the central shaft. At high impeller speeds  In unbaffled Containers 79 Vortex formation reduces mixing intensity by reducing velocity of the impeller relative to the surrounding fluid
  • 79.
    80 Prevention of VortexFormation Off-Centre Inclined Side-entry Push-pull Baffled Container
  • 80.
    Mixing of immiscible Liquids Mixingof immiscible liquids is carried in pharmacy mainly in the manufacturing of emulsions. The equipment emulsion is used calle d for preparing the emulsifier or homogenizer. Silverson mixer, colloid mill and rapisonic homogenizers are suitable for emulsification. 81
  • 81.
  • 82.
    Silverson Mixer-Emulsifier Principle: • Itproduces intense shearing forces and turbulence by use of high speed rotors. • The emulsifier head is dipped in the mixture of immiscible liquids. • The liquid mixture is sucked inside the emulsifying head due to suction and is dispersed in the form of fine globules when acted upon by the turbine blade and issued through the perforations from the head. 83
  • 83.
    SILVERSON HOMOGENIZER CONSTRUCTION: • Itconsists of long supporting columns and a central portion. • The central portion consists of a shaft which is connected to motor at one end and other to the emulsifying head. • The emulsifying head carries turbine blades. • The blades are surroundedby a mesh, which is further enclosed by a cover having openings. 84
  • 84.
    SILVERSON HOMOGENIZER • 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 blade at a very high speed. This creates a pressure difference. As a result, liquids are sucked into the emulsifier head from the center of the base and subjected to intense mixing action. Centrifugal force 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 ones. 85
  • 85.
    Silverson mixer - Emulsifier Uses: Used for the preparation of emulsions and creams of fine particle size.  Advantages: Silverson mixer is available in different sizes to handle the liquids ranging from a few milliliters to several thousand liters. • Can be used for batch operations as well as for continuous operations by incorporating into a pipeline, through which the immiscible liquids flow.  Disadvantages: Occasionally, there is a chance is clogging of pores of the mesh 86
  • 86.
  • 87.
    Semi-Solid Mixing • Semi solidsdosage 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 following mixers are helpful for mixing: • Agitator mixers: e.g.:- Sigma mixers and Planetary mixer. • Shear mixers: e.g.:- Triple roller mill and Colloidal mill. 88
  • 88.
    Mixing of semi- solids •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. Material that finds its way to 'dead' spots will remain there. 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, as diffusion and convection cannot occur. The forces required for efficient mixing are high and consumption of power is also high. Hence the equipment must be rugged constructed to exhibit dilatant tolerate propert y these forces. Some semisolids 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. 89
  • 89.
  • 90.