Industrial pharmacy Mixing Introduction Importance of mixing Types of mixtures Fluid mixing, its mechanisms and types of fluid mixers Semi-solid mixing, mechanism and equipments used Solid mixing, mechansims ans types of solid mixing equipments Introduction Importance of mixing Types of mixtures Fluid mixing, its mechanisms and types of fluid mixers Semi-solid mixing, mechanism and equipments used Solid mixing, mechansims ans types of solid mixing equipments

1. MIXING
S A M I A G H A N I
M . P H I L P H A R M A C E U T I C S

3. CONTENTS
• Introduction
• Importance of mixing
• Types of mixtures
• Fluid mixing, its mechanisms and types of fluid mixers
• Semi-solid mixing, mechanism and equipments used
• Solid mixing, mechansims ans types of solid mixing equipments

4. INTRODUCTION
• « Mixing is a process in which two or more ingredients in seperate or roughly
mixed conditions are treated so that each particle of any one ingredient is as
nearly as possible adjacent to a particle of each of the other ingredients »
defined by Perry and Chilton in 1973.
• Synonyms or other terms used for mixing « blending, mingling, amalgamation
or unification.
• It tends to results randomization of dissimilar particles within a system.
• Mixing aims at reducing non- uniformity in one or more of the properties of a
material in bulk.
• Whenever a product contains more than one component, mixing or blending
stage will be required in manufacturing process therefore the unit operation of
mixing is involved at some stage of production of practically every
pharmaceutical preparation.

5. IMPORTANCE OF MIXING
• Mixing is a fundamental process in most process sequences and is normally
carried out;
• To control heat and mass transfer
• To secure composition uniformity so that small sample withdrawn from a bulk
material represents the overall composition of mixtures.
• To improve single phase and multy phase systems.
• To promote physical and chemical reaction, such as dissolution in which
natural diffusion is supplemented by agitation.
• To get true solution after mixing of two miscible liquids.

6. AIM AND PHASE SYSTEMS IN MIXING
 Main aim of the mixing process is the production of a blend whose sample
reflects exactly, or at least by pre-defined accuracy, the ratio of the added
base materials
 Mixing operation may involve:
• single phase system (e.g., blending of miscible solutions or fast chemical
parallel reactions.)
 multiphase systems (e.g., solid powders, dispersion/suspension,
emulsification)

7. TYPES OF MIXTURES
Mixtures may be categorized into three types.
• Positive mixtures - Positive mixtures are formed from materials such as gases or
miscible liquids which mix spontaneously and irreversibly by diffusion without
the expenditure of energy, provided time is unlimited and tend to approach a
perfect mix. Although energy input by using mixing apparatus will shoten the
time required to obtain desired degree of mixing.
• 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. emulsions, creams and
suspension of solids and liquids, such as calamine lotion. Negative mixing is
demonstrated by biphasic system in which the phases differ in density.
• Any two phase system tends to seperate out quickly unless energy is expended
on them. Negative mixers are difficult to maintain and require high degre of
mixing s compared to positive mixtures.

8. CONTI…
• Neutral mixtures - Neutral mixtures are said to be static in behaviour, i.e. the
components have no tendency to mix spontaneously or segregate
spontaneously once work has been input to mix them (Usually of low viscosity
systems).
• Neutral mixing occurs when neither mixing nor demixing takes place unless the
system is acted upon by an external energy input. (Intermediate viscosity
systems)
• Examples of this type of mixture include mixed powders, pastes and
ointments. (high viscosity sytems)

10. FLUID MIXING AND ITS MECHANSIM
• Depending upon the relationship between the shear rate and the applied
shear stress, the fluids may be divided into:
 Newtonian Fluids
 Non-Newtonian fluids

11. TYPES OF FLUID FLOW
Newtonial flow
• For it the rate of shear (strain
produced in the structure of a
substance) is proportional to the
applied stress.
• Such fluid have dynamic
viscosity independent of
flow rate.
Non-newtonial flow
• Rate of shear is not proportional
to applied stress.
• These exhibit dynamic viscosity
that are a function of shear
stress.

12. liquid
mixing
mechanism
bulk transport
turbulent
flow
laminar flow
molecular
diffusion

13. LIQUIDMIXING
Liquid mixing is divided into following subgroup:
1. Mixing of liquid and liquid
i. Mixing of two or more miscible liquids
ii. Mixing of two or more immiscible liquids
2. Mixing of liquid & solid
i. Mixing of liquids & soluble solids
ii. Mixing of liquids & insoluble solids

14. BULK TRANSPORT
• The movement of relatively large portion of the material being mixed
from one location in the system to another.
• For bulk transport to be effective it must results in rearrangemznt or
permutation of various portions of materials to be mixed.
• This is usually accomplished by means of paddles, revolving blades, or
other devices within the mixer arranged so as to move adjacent volumes
of fluid in different direction, thereby shufling the system in three
dimensions.

15. TURBULENT MIXING
• It is the direct result of turbulent fluid flow which is characterized by a random
fluctuation of the fluid velocity at any given point within the system.
• The fluid velocity at a given instant may be expressed as the vector sum of its
component in the X, Y,and Z direction.
• With turbulence, the fluid has a different instantaneous velocities at different
location at same instant in time.
• Turbulent flow can be conveniently visualized as a composite of eddies of various
sizes.
• Scale of turbulence: size distribution of eddies within a turbulent region.

16. LAMINAR MIXING
• Streamline or laminar flow is frequently encountered when highly viscous fluid are
being processed.
• When two dissimilar liquids are mixed through laminar flow the shear that is
generated stretches the interface between them.
• If the mixer employed forces the layer back upon themselves ,the number of
layer, and hence the interfacial area increase exponentially with time.
• Mixers may also operate by simple stretching of fluid layers without significant
folding action.
• This process alone if implemented requires exceedingly long time for the
layers of different fluids to reach molecular dimensions.

17. MOLECULAR DIFFUSION
• Primary mechanism responsible for mixing at the molecular level is diffusion
resulting from the thermal motion of molecules.
• When it occurs in conjugation with laminar flow, molecular diffusion tends to reduce
the sharp discontinuities at the interface between the fluid layers
• Process if allowed for sufficient time results in complete mixing.
• Process is best described by Fick’s 1st law of diffusion:
dm/dt= -DA dc/dx
• Where the mass transport rate (dm/dt) across an interface of area (A) is proportional to
the concentration gradient (dc/dx) across the interface.
• D is the diffusion coefficient which depends upon variables such as fluid viscocity and
size of diffusing molecules.

18. EQUIPMENTS
Factors affecting selection of equipment/ mixers:
 Physical properties of the materials to be mixed…likedensity, viscosity,and
miscibility.
 Economic considerations regarding processing, e.g. Time required and
power expenditure necessary.
 Cost of equipment and its maintenance

19. SHAKER MIXERS
• There principle of mixing is agitation.
• This can be achieved by:
1. Oscillation (lab scale)
2. Rotation (industrial scale)
• Mixing efficiency us very variable and depends upon turbulence which further depends
upon properties of liquids (viscosity) and on the use of baffles.
• Therefore use of these mixers is limited and are not too effective.

20. IMPELLERS
• Distinction between impellers is made on the basis of :
A. Type of flow pattern they produce;
• Radial flow
• Axial flow
• Tangential flow
B. Shape and pitch of blades

21. FLOW PATTERNS INDUCED BY IMPELLERS: A; RADIAL
FLOW, B; AXIAL FLOW, C; TANGENTIAL FLOW

22. PROPELLERS
 Propellers primarily induce
axial/longitudinal flow and a very
little tangential flow.
 Intense turbulence occurs in the
immediate vicinity of the propellers.
 Operate at high speed i.e. 8000rpm
 They are most effective when they are run
at high speed in liquids of relatively low
viscosity.
 If viscosity is greater than 50P or 500cP
(viscosity of glycerine or castor oil) than they
are not effective.
 Due to high speed and axial flow, vortexing
and aeration (when air bubbles may
accumulate in liquid and can cause
oxidation) is major problem.
 To avoid this, impellers should be placed
deep into liquid and symmetry should be
avoided..

23. WAYS TO AVOID SYMMETRY
1. Propeller shaft may be offset from center.
2. May be mounted at an angle.
3. Shaft may be entered from either side of the vessel.
4. Use of push-pull propellers in which two propellers are mounted on same shaft with
opposite pitches.
5. Use of baffles.

24. TURBINES
 Blades do not have constant pitch throughout their length.
 When majorly radial and little tangential flow is desired blades set at 90-
degree angle to their shaft are employed and have high shear force.
 Shear force can further be increased by introducing a diffuser ring which
reduces vortexing too.
 Tilted blades produce axial flow similar to propellers.
 Suitable for viscous fluid( viscosity 1000 times greater than fluid in which
propellers operates.
 RPM and D/d ratio is somewhat lower than propellers.

25. PADDLES
 Normally operates at low speeds ( 50 to
100 rpm) that do not demands baffles.
 Blade are flat and have a large surface
area in relation to tanks in which they
are employed.
 Circulation is primarily tangential with
very little longitudinal which can be
increased by using paddles with slight
pitch and thus can be used for viscous
fluid mixing.
 Effectively mix viscous liquid and
semisolids.

27. AIR JETS:
 Subsurface jets of air or less
commonly of some other gas, are
effective mixing devices for certain
liquids.
 Liquid must be of low viscosity, non
foaming, unreactive with gas, and
nonvolatile.
 Jets are so arranged that the buoyancy
(upwaed force exerted by a fluid) of
bubbles lift liquids from the bottom to
the top of the mixing vessel

29. FLUID JETS:
 When liquids are to be pumped into a tank for mixing, the
power required for pumping often can be used to accomplish
the mixing operation.
 Fluid are pumped through nozzles arranged to permit good
circulation of material throughout the tank.
 They create somewhat turbulent flow in the direction of their axis.

31. SEMI-SOLID MIXING
• There is a very little difference between highly viscous liquid and a semi-solid material.
• Newtonian material are easy to mix
• Non-newtonian are difficult to mix.
• When liquid is mixed with a sokid/powder, different states of semi-solids are achieved
and than finally mixed state.

32. QUASI-SOLID MIXING
• Mechansim pf semisolid mixing:
1. Powder state (initial powder)
2. Pellet state (addition of small amount of liquid, solid balls up and form pellets. Mas
has granular appearance at this stage, homogenization attainment is low, incase of
tablet formation, mixing is done until this stage and granules are prepared.)
3. Plastic state (further addiotion of liquid results loss of granular appearance and
mixture becomes homogenous and plastic like properties appear in mixture like
materials are difficult to shear but homogenization is rapid, shear forces are needed
to mix plastic material, flow at low stress but break needs high stress)

33. MIXING MECHANISM IN PLASTIC
STATE
• Application od shear forces cause movement of a part of material
• Displacment of part of material by shearing action
• Continuing shear displace it more
• Mass distortion
• Followzd by further shearing
• Cycle repeats

34. CONTI…
4. Sticky state (continuous addition of liquid results in paste like appearance, mass
flow is easy even under low stresses, homogeneity is achieved slowly, mass is shiny and
adheres to solid surface.)
5. Liquid state (further addition of liquid results in decresed consistency untill a fluid
state is achieved, rate of homogenization is rapid, mixture flow on its own weight)
In mixing procedure, rate and degree of addition of liquid plays an important role, lumps
should not form.

35. EQUIPMENTS
• Kneaders/ agitator mixers
1. Sigma-blade mixers
2. Planetary mixers
3. Mulling mixers
• Mills/ shear mixers
1. Roller mill
2. Collidal mill
• Ultrasonic mixers

36. SIGMA BLADE MIXERS
• Called so because 2 blades (moving with different velocities) attached are in sigma shape.
• Have counter rotating blades of heavy arms that work the plastic mass
• Blades rotate tangentially with a speed ratio of about 2:1 and are hollow thus generating
heat which is necessary to reduce viscosity of semisolids
• Shape and differecne in rotational speed of the blade facilitate lateral pulling of material
and impart kneading and rollling action on the matarial.
• Shear froces are lso generated by high viscosity of mass thus effective in deaggregation as
well as distrubtion of solids in liquid vehicle.
• Suitable for heavy masses like pill masses, granular masses, ointment masses.
• Incorporation of air is problematic whih can be overcomed by operating in enclosed system
and with reduced pressure.

38. PLANETARY MIXERS
• Imparts planetary mixing action.
• Mixing element rotates round the circumference of mixer’s container (movement of
blades) as well as simultaneously rotatign about its own axis (movement of vessel but
at lower speed).
• Double rotation and offset position reduces dead zone and avoid vortex formation.
• Can handle material of greater consistency.
• Agitator arms are designed to give a pulling action and shape and movement is such
that material is cleared from all sides and corners of mixing vessel.

40. ROLLER MILL AND COLLOIDAL MILL
• Machine used for size reduction can b used for mixing of material but mixing efficiency is
poor
• Three roller types are preferred which are composed of hard, abrasion-resistant material,
and arranged to come inclose proximity of eachother, distance between rollers is
adjustable.
• Colloidal mill has high speed rotor (3,000-20,000 rpm) and stator having adjustable
clearance ranging from 0.002-0.03inches.
• Rotor and stators may be either smoothed surface of rough surface.
• With smooth surface rotors and stators, there is a thin uniform film of material between
them which is subjected to maximum amount of shear.
• Rough surfaced mills ad. Intense eddy currents, turbulence and impaction to the shearing
action; useful with fibrous material ecause they may tend to interlock and clog smooth
surfaced mills

42. ULTRASONIC MIXERS
• Mixing or prep of emulsion, done by exposing material to ultrasonic rays.
• If a liquid is subjected to ultrasonic vibration, alternate regions of contration and
refraction (change in direction of movement) will be made.
• Cavities are formed in refraction regions which will collapse resulting in emulsification
and uniform mixing.

43. SOLID MIXING
• Fall under the cateory of neutral mixing.
• Principle of solid mixing:
• Can be understood by mixing two different coloured powdered components of same
shape, size and density.
• A: complete segregation
• B: Perfect mix
• C: random mix

45. Mixing mechanisms
Convective mixing
Shear mixing
Diffusive mixing
depends upon material
density, particle size,
shape, attraction,
proportion of material,
mixers speed, time,
volume, order

46. SCHEMES/ REGIMES OF MIXING FLOW
• Slipping (occurs when granular bed undergoes solid bed rotation and than slides, usually against
rotating tumbler walls)
• Avalanching (or slumping, seen at slow tumbling speed, in this regime a group of powder travel down
the free surface and comes to rest before a new group is released from the above)
• Rolling (at higher tumbling speed discrete avalanches give way to continuous flow at the surface of
the blend)
• Cascading (powder beneath cascading layers rotates nearly as a solid body with the blende untill it
reaches the suface)
• Cataracting (at high speed this regime is observed, once the particles are not in contact with the walls
or blades they follow the same trajectory and do not roll by avalanching, characterized by projections
of particles in the air)
• Centrifugation (at further high speed, the pwder centrifuges against tumbler wall)

47. CONVECTIVE MIXING
• Analogous to bulk transport (discussed in fluid mixing mechanisms).
• Can occur by inversion of powder bed, or by any other method of moving relatively
large mass of material from one part of powder bed to the other.
• Although effectively intersperse powders in tumbler within tens to hundreds of
revolutions and is fastest and effecient mixing mechanism, it suffers from barriers to
mixing that prevent interaction with surronding materials (as in case of liquids).

48. SHEAR MIXING
• Due to the forces that are within the particulate mass.
• Random motion of particles causes the powder bed to change their position relative to
one another.
• Occurs at interfaces of dissimilar regions that are undergoing shear.
DIFFUSIVE MIXING

49. EQUIPMENTS/ MIXERS
Agitating mixers
• ribbon mixers/
blenders
• planetary mixers
• Nauta mixers
• fluidized air mixers
Tumbling mixers
Double cone
mixers
V-shaped mixers

50. AGITATOR MIXERS
• Employ stationary container to hold the material and bring about mixing by moving
screws, paddles or blades.
• Unlike tumbling mixers, these do not entirely depend upon gravity, so useful in mixing
solids that have been wetted and are in shear or plastic state.
• Setted-up high shear forces are effective in breaking up lumps or aggregates.
• Helps in attainig uniform size and density powder mix.

51. RIBBON MIXER/ BLENDER/ DOUBLE
HELICAL MIXER
• Used to mix liquids with solids, dry granules, wet granules, dry powders and semisolids.
• Consists of horizontal cylidrical tank usually opening at the top and fitted with helical
blades or ribbons.
• Blades are mounted on horizontal axle by struts and rotated to circulate the material to
be mixed.
• Highly homogenous mixtures can be obtained by prolonged mixing even when
components differ in particle size, shape, density or even tendecy to aggregate.
• Disadvantage: difficult to clean, difficult to discharge matter to be mixed.

53. PLANETARY MIXERS
• Similar to semi-solid mixing.
• Imparts planetary mixing action.
• Mixing element rotates round the circumference of mixer’s container (movement of
blades) as well as simultaneously rotatign about its own axis (movement of vessel but
at lower speed).
• Double rotation and offset position reduces dead zone and avoid vortex formation.
• Can handle material of greater consistency.
• Agitator arms are designed to give a pulling action and shape and movement is such
that material is cleared from all sides and corners of mixing vessel.

54. NAUTA MIXER/ HIGH SHEAR MIXER
• Vertical screw mixer which imparts 3-D mixing.
• Screw assembly is mounted in conical chamber with screw moving in planetary motion and also lifting
the powder to be blendid from bottom to top.
• Originally designed as powder or semi-solid mixers but now-a-days also used as mixer granulators.
(Basic operation: powder mixing- incorporating liquid-granulating agent, wet massing; drying as hot
dry air passed through wet material.)
• Accessory equipment designed to monitor and control the processor operation includes choppers, air
filters, lump breaker, temperature monitor, nuclear non-contact density guage, an ammeter or
wattmeter, infrared misture analyzer and sampling system
• Advantage: require little floor space, easy to wash.
• Disadcantage: high speed produces charge on particles (remedy: pass nitrogen that will dissipate
charges on particles).

56. TYPES OF HIGH SHEAR MIXERS
• Gral mixer: modification of industrial planetary mixers, only difference is that this
assembly contains two mixin devices; large mixing arm (shaped to rounded
centrifugation of bowl, provides large scale mixing and motion to the powder) and
smaller chopped blade (entering off-center from the mixing arm and located above it.
Advantage: easy to clean up
• Diosna mixer: bowl is mounted in a vertical position, and a high speed mixer blade
that revolves around the bottom of the bowl and a high speed choppr blade which
fuctions as a lump and agglomerate breaker.

58. FLUIDIZED AIR MIXER
• Modifcation of vertical impeller.
• Impeller is replaced by rapidly moving stream of air fed into the bottom of shell.
• Powder body id fluidized and mixing is accomplished by circulation and over)tumbling
in the bed.
• 8 air blasts, each air blast is of 2 seconds, having gap of 1 second in each two air blasts.
• Loss of material prevented, mixing time reduced,

59. TUMBLING MIXERS
• Octahedral or various geometric forms of cylinder causes movement in nearly all
directions.
• Types: twin shell, cube, drum, octahedral shape mixer
• Mixing efficency depends upon angle of repose :
Angle of repose more, poor flowing thus no proper mixing
Angle of repose less, better flow proerties, proper mixing.
Cylindrical vessels rotate but shear forces and end to end movements are low, to
overcome this, baffles (flattened plates) are introduced or shape of vessel is changed.

60. • Different designs of vessels can be used e.g. double cone mixer, V-shaped mixer, Y-
shaped mixer and diamond shape mixer.
• Feautres of tumbling mixers:
Uniform mixing, short mixing time, work with interlocked system, autoloading occurs,
can operate in vaccum suction system and mixes dry granules.
Used in powder as well as granule mixing. Octahedral shape produces assymetrical
movement resulting in surface charges reduced.

61. DOUBLE CONE MIXER
• Same principle as tumbling but differs in geometry.
• Inside cone, baffles in the middle, when powders or granules pass results in better
mixinf
• Give uniform mixing, simple structure, have safety and interlock system, can operate in
vaccum system, auto loading occurs.

62. V-SHAPED MIXERS
• Facilitates asymmetric rotation.
• Enables powder to seperate in two cones by rotating cones rapidly which will merge
into one cone again.
• Due to this repeated merging and seperating phenonmenon, best mixing takes place.

64. HOMOGENIZATION
Homogenization is the process of converting
non-uniform mixture to a colloidal state or a
uniform mixture. It is done by reducing
particle size of mixtures or uniform dispersion
of the mixtures making the product
homogenous.
e.g: converting coarse emulsion to colloidal
emulsion
Homogenizers are used for the preparation
of biphasic systems like suspensions,

65. HOMOGENIZERS
Modified Turbines: It consists of turbine &
stator at a certain distance in the mixer. The
rotation of turbines at very high speed
creates a pressure difference & reduces the
particle size. The particles & fluids pass
through the stator & turbines which produces
mechanical forces to obtain uniform or
homogenized mixture.

66. Pressure Homogenizer: It consists of high
pressure pump fitted to stainless steel fluid tank.
The high pressure is responsible for
homogenization of solid dispersed in the liquid.
Ultrasonic Homogenizer is an example of
waves (frequency above
pressure homogenizer where ultrasonic
20000 Hz) are
generated for mixing or uniform dispersion of the
mixtures. The ultrasonic waves produces shear
effect responsible for size reduction &
homogenization. It is used primarily for
emulsification.