1. MIXING : Theory and Equipment
Pharmaceutical Engineering
PHR 312
Shahana Sharmin
BRAC University

2. Mixing: Theory and Equipment
Introduction
Mixing is defined as a process that tends to result in a randomization of dissimilar particles within a system.
The term MIX means to put together in one mass.
The term BLENDING means to mix smoothly and inseparably together during which a minimum energy is imparted to the bed.
The terms MIXING and BLENDING are commonly used interchangeable in the pharmaceutical industry.
Mixing: Theory and Equipment

3. Definition Mixing is Randomization of dissimilar particles. e.g. -
Spatulation,
Trituration,
Tumbling and
Geometric dilution

4. Definition
Mixing may be defined as the process in which two or more than two components in a separate or roughly mixed condition are treated in such a way so that each particle of any one ingredient lies as nearly as possible to the adjacent particles of other ingredients or components. This process may involve the mixing of gases, liquids or solids in any possible combination.

5. Application and example of Mixing
Mixing of powders in varying proportions prior to granulation or tabletting.
Dry mixing of the materials for direct compression in tablets
Dry mixing of the materials for direct compression in tablets.
Dry blending of powders in capsules and compound powders (insufflations).

6. Application and example of Mixing
Blending of powders in cosmetics in the preparation of face powders, tooth powders .
Dissolution of soluble solids in viscous liquids for dispensing in soft capsules and in the preparation of syrups
Mixing of two immiscible liquids for preparation of emulsions.

7. Depending on the flow properties of materials, solids are divided into two types:
Cohesive materials - These are characterized by their resistance to flow through openings for e.g. wet clay.
Noncohesive materials – These materials flow readily such as grain, dry sand, plastic chips etc.

8. Objectives????
To ensure that there is uniformity of composition between the mixed ingredients.
To initiate or to enhance the physical or chemical reactions e.g. diffusion, dissolution etc.

9. Types of mixtures: Mixtures may be classified as follows:
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.

10. Types of mixtures:
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. Examples of this type of mixture include mixed powders, pastes and ointments.

11. Classification of mixing
Mixing of solids
Mixing of liquids
Mixing of immiscible liquids
Mixing of semisolids
Mixing: Theory and Equipment

12. Mixing: Theory and Equipment
Mixing of solids
In the manufacture of tablets or granules normally a number of additives are added. Therefore mixing of powder becomes essential part of the process.
Mixing is considered as a critical factor, especially in case of potent drugs and low dose drugs where high amounts of adjuvants are added.
The diverse characteristics of particles such as size shape volume surface area density porosity flow charge contribute to the solid mixing.
Depending on their flow properties solids are divided into two classes as cohesive and non cohesive.
Mixing: Theory and Equipment

13. Interparticle interactions & segregation
1.Inertial forces:
These forces hold neighboring particles in fixed relative position.
E.g.: Vander Waal forces, electrostatic forces, surface forces.
Surface forces:
Cohesive forces and frictional forces results in surface-surface interactions which resist the movement of particles, hence they should be minimal.
During mixing, the particles develop surface charge which produce particle-particle repulsions, which make random mixing impossible.
These depend on surface area, surface roughness, polarity, charge, moisture.
Mixing: Theory and Equipment

14. Mixing: Theory and Equipment
Segregation
Poor flow properties.
Particle size difference.
Difference in mobilities.
Differences in particle density and shape.
Transporting stage.
Dusting stage.
It may occur even after mixing.
Mixing: Theory and Equipment

15. Mixing: Theory and Equipment
2. Gravitational forces
Improve the movement of two adjacent particles or groups of particles
When particle-particle collisions occur , exchange of momentum is achieved continuous exchange or distribution of momentum between transitional and rotational modes is necessary for effective mixing
Efficiency of momentum transfer depends on
Elasticity of the collisions
Coefficient of friction
Surface area of contact
Centrifugal forces
Mixing: Theory and Equipment

16. Mechanism of mixing of solids
1. Convective mixing/Macro mixing: Inversion of the powder bed using blades or paddles or screw element, in which large mass of material moves from one place to another. 2. Shear mixing: In this type, forces of attraction are broken down so that each particle moves on its own between regions of different components and parallel to their surface. 3. Diffusion mixing/Micro mixing: Involves the random motion of particle within the powder bed, thereby particles change their position relative to one another.
Mixing: Theory and Equipment

17. Mixing: Theory and Equipment
Mixing process - steps
In the solid-solid mixing operations , four steps are involves. These are:
Expansion of the bed of solids
Application of 3-dimensional shear forces to the powder bed.
Mix long enough to permit true randomization of particles.
Maintain randomization.
Mixing: Theory and Equipment

18. Mixing: Theory and Equipment
The law of mixing appears to follow first order,
𝑴=𝑨 (𝟏− 𝒆 −𝒌𝒕 )
Where M = degree of mixing after time t,
T = time
A and k = constants
A and k depends on the
Mixer geometry
Physical characteristics of the powders and
Proportion of the material being mixed.
Mixing: Theory and Equipment

19. Mixing: Theory and Equipment
Degree of mixing
Ideal mixing or perfect mixing:
Acceptable mixing:
Random mixing
Ordered mixing
Mechanical means of ordered mixing
Adhesion means of ordered mixing
Coating means of ordered mixing
Mixing: Theory and Equipment

20. Mixing: Theory and Equipment
Adhesion means of ordered mixing:
Coating means of ordered mixing:
Mixing: Theory and Equipment

21. Statistical parameters
Arithmetic mean:
Size distribution is calculated
Arithmetic mean ȳ= 𝑖 𝑛 𝑦 𝑖 𝑛
Standard deviation:
Used to know the spread of dispersion.
Standard deviation 𝜎= 𝑖 𝑛 ( 𝑦 𝑖 −ȳ) 2 (𝑛−1)
Mixing should be continued until the amount of the active drug that is required is with in ± 3 SD units that of found by assay in a representative number of sample dose.
Relative standard deviation:
It replace the S.D as a measure of sample uniformity.
Useful for comparing the efficiency of two or more mixing operations or different sample size or different composition.
𝑝𝑒𝑟𝑐𝑒𝑛𝑡 𝑟𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝑆.𝐷= 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 𝑑𝑒𝑣𝑖𝑎𝑡𝑖𝑜𝑛(𝜎) 𝑚𝑒𝑎𝑛 ȳ 𝑋 100
Mixing: Theory and Equipment

22. Mixing: Theory and Equipment
Mixing indices
Involves the comparison of SD of sample of a mixture under study with the estimated standard deviation of a completely random mixture.
It can be expressed in two ways:-
𝑀= 𝜎 𝑅 𝜎 or 𝑀= 𝜎 𝑜 −𝜎 𝜎 𝑜 − 𝜎 𝑅
Where,
M = mixing index
𝜎 𝑅 = standard deviation of the random blend
𝜎 = standard deviation of the sample blend
𝜎 𝑜 = standard deviation of the unmixed powder
Mixing: Theory and Equipment

23. Statistical evaluation
Objectives:
To compare the efficiency of two or more mixing operations.
To compare the efficiency of two or more equipment.
To follow the mixing process with time.
To optimize processing parameters
To investigate the mechanism of mixing in a given piece of equipment.
Sample size:
Approximately a unit dose of the final product.
Number of samples:
Required – 30
Ideal – 100
Economical sampling – 20
Sample collection:
At different intervals when the blend is in motion.
After blending is completed
Sample utilization:
Scooping sampling
Thief probing
Sampling methods:
Non destructive
destructive
Mixing: Theory and Equipment

24. Factors influencing mixing
Nature of surface: Rough surface of one of the components does not induce satisfactory mixing.
Material density: Demixing is accelerated when the density of the smaller particles is higher or when the mixing process is stopped abruptly.
Particle size: It is easy mix two powders having approximately the same particle size. The variation of particle size can lead to segregation.
Particle shape: The ideal particle is spherical in shape for the purpose of uniform mixing.
Mixing: Theory and Equipment

25. Factors influencing mixing
Particles charge: Some particle exert attractive forces due to electrostatic charges on them.
Particle attraction: Sometimes particles may separate and segregate due to particle attraction.
Proportions of materials to be mixed: The best results can be obtained if two powders are mixed in equal proportion by weight and by volume.
Mixing: Theory and Equipment

26. Mixing: Theory and Equipment
Criteria:
Powder bed should not be filled for more than 60%
Particles should be subjected to movement in three directions
Shearing force should be sufficient to prevent aggregation.
There should be no centrifugal effect
Forces should not cause breakage of the particles.
The mixing process should be stopped abruptly.
Mixing: Theory and Equipment

27. Classification of equipment for solid mixing
Based on flow properties:
1.Free flowing solids:
e.g.: V cone blend , Double cone blender
2.Cohesive solids:
e.g.: Sigma blender, Planetary mixer
Based on scale of mixing:
1.Batch type(small scale):
e.g.: Mortar and pestle, V cone blender, Double cone blender, Ribbon blender, Sigma blender, Planetary paddle, Fluidized mixer
2.Continuous type(large scale):
e.g.: barrel type, zigzag type
Mixing: Theory and Equipment

28. S.no. Nature of mixer Examples Mechanism of mixing1
Batch type
Mortar pestle
Trituration 2
Tumbling mixers or cylindrical mixers with no mixing blade
Double cone blender
V cone blender
Tumbling action 3
Tumbling mixer with a mixing blade
V cone blender double cone blender
Tumbling action as well as shearing with blade 4
Static mixers
Ribbon blender
Sigma blender
Planetary paddle
Stationary shell and rotating blade 5
Air mixers or fluidized mixers
Fluidized mixer
Air supported blending 6
Continuous type
Barrel type
Zigzag type
Rotating shell with rotating blade
Mixing: Theory and Equipment

29. Tumblers or cylindrical blenders with no mixing blade
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.
Edge of 27 degrees is good for mixing.
Efficiency of a tumbler mixer highly depends on the speed of rotation. It should be critical and optimum.
Slow rotation- no intense tumbling, No cascade motion, Not enough shear rates are applied.
Rapid rotation-sufficient centrifugal action to the powder to the side of the mixer, more dusting and segregation of fines is possible.
Rate of rotation depends upon size , shape of the tumbler and nature of the material to be mixed. Common range is rpm.
Mixing is done by tumbling motion, which is accentuated by virtue of the shape of the container.
Mixing: Theory and Equipment

30. Twin shell blender or V cone blender
It is V shaped and made up of stainless steel or transparent plastic.
Material is loaded through shell hatches and emptying is normally done through and apex port.
The material is loaded approximately 50-60% of the total volume.
Small models – 20 kg , rotate at 35rpm
Large models – 1 ton, rotate at 15rpm
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.
Mixing: Theory and Equipment

31. Mixing: Theory and Equipment
Double cone blender
It consists of double cone on rotating shaft.
It is usually used for small amount of powders.
It is efficient for mixing powders of different densities.
Material is loaded 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 rpm.
Mixing occurs due to tumbling motion.
Double cone blender
Mixing: Theory and Equipment

32. Mixing: Theory and Equipment
Advantages of V cone blender and double cone blenders:
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 and double cone blenders:
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 required for the addition of low dose active ingredients.
Mixing: Theory and Equipment

33. Tumbling blenders with agitator mixing blades
Mixing: Theory and Equipment

34. Mixing: Theory and Equipment
Advantages of tumblers with blades:
Baffles are useful 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 ingredients.
Disadvantages of tumblers with blades:
Attrition is large, size reduction of friable particles results.
Scale-up can prove a problem, because general principles of scale-up do not work
Cleaning may be a problem, because agitator assembly must be removed and the packing should be replaced for a product changeover
Potential packing (sealing) problems occur.
Mixing: Theory and Equipment

35. Mixing: Theory and Equipment
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. An equilibrium state of mixing can be achieved.
Construction:
Consists of horizontal cylindrical trough usually open at the top. It is fitted with two helical blades, which are mounted on the same shaft through the long axis of the trough.
Blades have both right and left hand twists.
Blades are connected to fixed speed drive.
It can be loaded by top loading and emptying is done through bottom port.
Mixing: Theory and Equipment

36. Mixing: Theory and Equipment
Working:
Uses:
Used for mixing of finely divided solids, wet solid mass, and plastic solids.
Uniform size and density materials can be easily mixed.
Used for solid – solid and liquid – solid mixing.
Mixing: Theory and Equipment

37. Mixing: Theory and Equipment
Advantages of ribbon blender:
High shear can be applied by using perforated baffles, which bring about a rubbing and breakdown aggregates.
Headroom requires less space.
Disadvantages of ribbon blender:
It is a poor mixer, because movement of particles is two dimensional..
Shearing action is less than in planetary mixer.
Dead spots are observed in the mixer, though they are minimum.
It has fixed speed drive.
Mixing: Theory and Equipment

38. Mixing: Theory and Equipment
Sigma blade mixer
Principle – shear. Inter meshing of sigma blades creates high shear and kneading action.
Construction and working:
It consists of double tough shaped stationary bowl.
Two sigma shaped blades are fitted horizontally in each tough of the bowl.
These blades are connected to a fixed speed drive.
Mixer is loaded from top and unloaded by tilting the entire bowl.
The blades move at different speeds , one about twice than 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 tough resulting cascading action.
Perforated blades can be used to break lumps and aggregates which creates high shear forces.
The final stage of mix represents an equilibrium state.
Sigma blade mixer
Mixing: Theory and Equipment

39. Mixing: Theory and Equipment
Uses of sigma blade mixer:
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.
Advantages of sigma blade mixer:
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.
Disadvantages of sigma blade mixer:
Sigma blade mixer works at a fixed speed.
Mixing: Theory and Equipment

40. Mixing: Theory and Equipment
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.
Mixing: Theory and Equipment

41. Mixing: Theory and Equipment
Uses :
Break down agglomerates rapidly.
Low speeds are used for dry blending and fast for wet granulation.
Advantages:
Speed of rotation can be varied at will.
More useful for wet granulation process.
Disadvantages:
Mechanical heat is buildup within the powder mix.
It requires high power.
It has limited size and is useful for batch work only.
Mixing: Theory and Equipment

42. Air mixer or Fluidized mixer
Principle:
The air movement is used for mixing powders. Air is admitted at its base at an angle which gives tumbling action and spiral movements to the powder. Thus mixing is achieved.
Construction:
It consists of stationary vessel which may be horizontal or vertical which is made up of stainless steel.
A wire mesh is placed at the bottom of the vessel which acts as support for placing the materials.
Air is allowed from beneath the mesh and circulated by using a fan.
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Mixing: Theory and Equipment

43. Advantages of fluidized mixer:
Reduced mixing time.
Mixing is intimate and efficient
Useful for drying and wet massing.
Also useful for coating with some modifications.
Mixing: Theory and Equipment

44. Barrel type continuous mixer
Principle:
Rotating shell keeps the material under tumbling motion. When the material approach the mid-point of the shell, another set of baffles causes part of the material to move towards the direction of inlet end allowing the remaining part to move forward. This process continuous up to discharge end, while another set of baffles guide the material to the discharge port.
Construction:
Resembles large cement mixer.
Baffles are fitted to the inner surface of the shell.
Shell is fixed to a shaft, which is allowed to rotate using electrical power.
Side openings are provided on each side for charging and discharging of the material.
Barrel Type continuous mixer
Mixing: Theory and Equipment

45. Zigzag continuous blender
Principle :
Material undergoes tumbling motion.
It is rotating shell type having several V shaped blenders connected in series.
When V section is inverted the material splits into two portions ; one half moves backward while another half moves forward.
As the first V section clears the charge, a fresh feed enters, hence used for continuous blending.
Zigzag continuous blender
Construction :
It consists of a long shell, which takes the shape of several V shaped blenders connected in series.
At one end of the shell a chamber for feeding is attached.
The other end allows the discharge of material
The shell is inclined towards to discharge end.
Mixing: Theory and Equipment

46. Applications of solid mixing
Involved in the preparation of many types of formulations.
It is also an intermediate stage in the production of several dosage forms.
Wet mixing in the granulation step in the production of tablets and capsules.
Dry mixing of several ingredients ready for direct compression as in tablets.
Dry blending of powders in capsules, dry syrups and compound powders.
Production of pellets for capsules.
Mixing: Theory and Equipment

47. Mixing: Theory and Equipment
Mixing of Fluids
Mechanism:
Bulk transport: Movement of large portion o a material from one location to another location in a give system. Rotating blades and paddles are used.
Turbulent mixing: Highly effective, mixing is due to turbulent flow which results in random fluctuation of the fluid velocity at any given point within the system. Fluid velocity at a given point changes in 3 directions (X, Y and Z).
Laminar mixing: Mixing of two dissimilar liquids through laminar flow, i.e., applied shear stretches the interface between them. Suitable for liquids which require moderate mixing.
Molecular diffusion: Mixing at molecular level in which molecules diffuse due to thermal motion.
Mixing: Theory and Equipment

48. Mixing Apparatus for fluids
A Container and
A Mixing Device or
Impeller
Mixing: Theory and Equipment

49. Mixing: Theory and Equipment
Mixing Device
Based on shape and pitch , the are classified into 3 types,
Propellers
Turbines
Paddles
Mixing: Theory and Equipment

50. Mixing: Theory and Equipment
Propellers
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 are more propellers are used for deep tank.
Size of propeller is small and may increased up to 0.5metres depending upon the size of the tank.
Small size propellers can rotate up to 8000rpm and produce longitudinal movement.
Mixing: Theory and Equipment

51. Mixing: Theory and Equipment
Advantages of propellers: Used when high mixing capacity is required. Effective for liquids which have maximum viscosity of 2.0pascals.sec or slurry up to 10% solids of fine mesh size. Effective gas-liquid dispersion is possible at laboratory scale. Disadvantages of propellers: Propellers are not normally effective with liquids of viscosity greater than 5pascal.second, such as glycerin castor oil, etc.,
Mixing: Theory and Equipment

52. Mixing: Theory and Equipment
Turbines
A turbine consists of a circular disc to which a number of short blades are attached. Blades may be straight or curved.
The diameter of the turbine ranges from 30-50% of the diameter of the vessel.
Turbines rotates at a lower speed than the propellers (50-200rpm).
Flat blade turbines produce radial and tangential flow but as the speed increases radial flow dominates. Pitched blade turbine produces axial flow.
Near the impeller zone of rapid currents, high turbulence and intense shear is observed. Shear produced by turbines can be further enhanced using a diffuser ring (stationary perforated ring which surrounds the turbine).
Diffuser ring increase the shear forces and liquid passes through the perforations reducing rotational swirling and vortexing.
Mixing: Theory and Equipment

53. Mixing: Theory and Equipment
Advantages of Turbines:
Turbines give greater shearing forces than propellers through the pumping rate is less. Therefore suitable for emulsification.
Effective for high viscous solutions with a wide range of viscosities up to 7.0 Pascal. Second.
In low viscous materials of large volumes turbine create a strong currents which spread throughout the tank destroying stagnant pockets.
They can handle slurries with 60% solids.
Turbines are suitable for liquids of large volume and high viscosity, if the tank is baffled.
Mixing: Theory and Equipment

54. Mixing: Theory and Equipment
Paddles
A paddle consists of a central hub with long flat blades attached to it vertically.
Two blades or four blades are common. sometimes the blades are pitched and may be 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 100rpm.
They push the liquid radially and tangentially with almost no axial action unless blades are pitched.
In deep tanks several paddles are attached one above the other on the same shaft.
At very low speeds it gives mild agitation in unbaffled tank but as for high speeds baffles are necessary.
Mixing: Theory and Equipment

55. Mixing: Theory and Equipment
Uses of paddles:
Paddles are used in the manufacture of antacid suspensions, agar and pectin related purgatives, antidiarrheal mixtures such as bismuth-kaolin.
Advantages of paddles:
Vortex formation is not possible with paddle impellers because of low speed mixing.
Disadvantages of paddles:
Mixing of the suspension is poor therefore baffled tanks are required.
Mixing: Theory and Equipment

56. Flow pattern during mixing
Tangential component or circular:
Acts in the direction tangent to the circle of rotation around the impeller shaft. If shaft is placed vertically and centrally, tangential flow follows a circular path around the shaft and creates a vortex in the liquid.
Radial component:
Acts in the direction vertical to the impeller shaft. Excessive radial flow takes the material to the container wall then material falls to the bottom and rotate as the mass beneath the impeller
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Mixing: Theory and Equipment

57. Axial component or longitudinal or vertical: Acts in the direction parallel to the impeller shaft. Inadequate longitudinal component causes the liquid and solid to rotate in layers without mixing. Adequate longitudinal pattern is best used to generate strong vertical currents particularly when suspending solids are present in a liquid.
Impeller type
Flow component
Propellers
Axial
Turbines
Axial or tangential or both
Paddles
Radial and tangential
Paddles with pitch
Radial, tangential and axial
Mixing: Theory and Equipment

58. Mixing: Theory and Equipment
Vortex formation
A strong circulatory flow pattern sometimes manifests into formation of a vortex near the impeller shaft.
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 tanks
Mixing: Theory and Equipment

59. Disadvantages of vortex formation
Vortex formation reduces mixing intensity by reducing velocity of the impeller relative to the surrounding fluid.
When vortex reaches the impeller, air from the surface of the liquid are drawn and air bubbles are produced.
Air bubbles in the fluid can create uneven loading of the impeller blades.
Entrapped air causes oxidation of the substances in certain cases.
Mixing: Theory and Equipment

60. Prevention of vortex formation
Impeller should in in any one of the position that can avoid symmetry such as off central, inclined, side entering, etc., and should be deep in the liquid.
Baffled containers should be used. In such case impeller can be mounted vertically at the center.
Mixing: Theory and Equipment

61. Mixing: Theory and Equipment
Two or more impellers are mounted on the same shaft where greater depth is required. This system is known as push and pull mechanism. The bottom impeller is placed about one impeller diameter above the bottom of the tank. It creates zone of high turbulence.
Mixing: Theory and Equipment

62. Mixing: Theory and Equipment
Tank other than cylindrical in shape are used to prevent vortex formation. However, such shapes may facilitate the formation of dead spots
Mixing: Theory and Equipment

63. Return flow with Draft tubes
Draft tubes are placed to control the direction and velocity of the flow to the impeller.
These are mounted around the propeller. In case of turbines, draft tubes are mounted immediately above the impeller.
Uses:
Draft tubes are fitted to equipment used in the manufacture of certain emulsions.
When solid particles tend to float on the surface of the liquid, they are dispersed using draft tubes.
Air jet mixers of continuous mixing of liquids employ draft tubes.
Disadvantage:
Draft tubes add to the fluid friction in the system. These reduce rate of flow.
Mixing: Theory and Equipment

64. Factors influencing mixing of liquids in tanks
Material related factors-
Properties of liquids: physical properties of materials to be mixed.
e.g.: Density, Viscosity and miscibility.
Equipment related factors-
Shape of impeller: Propeller type, straight, vertical, curved, or pitched.
Position of impeller: Central, off-center, side entry, vertical or inclined etc.,
Shape and size of the container: cylindrical or other geometric forms. Presence or absence of baffles.
Cost of equipment and its maintenance.
Process related factors-
Speed of rotation of the impeller.
Time required for mixing.
Amount of power that can be expended.
Ease of operation.
Batch size.
Mixing: Theory and Equipment

65. Equipment for Liquid mixing
Air jet mixer
Jet mixer
Flow mixer or line mixer or pipe mixer
Mixing: Theory and Equipment

66. Mixing: Theory and Equipment
Air jet mixer
Principle:
When compressed air jets are passes rom the bottom of a vessel, air bubbles are formed in the liquid phase. The buoyancy of the bubbles lifts the liquids, which are confines to the central portion due to the presence of drat tubes. The liquids flow down from the periphery of the vessel and enter from the bottom due to suction effect.
Construction:
Compresses air or suitable gas is allowed to pass at high pressure from the inlet provided at the bottom of the tank.
This causes buoyancy of the bubbles which lifts the liquid rom bottom to the top of the vessel.
Mixing: Theory and Equipment

67. Mixing: Theory and Equipment
Jet mixer
It consists of a vessel and a mixing device known as Jet.
A typical jet-mixing system has 12 jets arranged radially in a cluster in the centre of the mixing tank. The cluster of jets is called an eddy jet mixer.
An individual jet has two concentric nozzles with a suction chamber between them.
A single eddy jet mixer may have jets, but is the usual configuration.
Likewise, a single tank may have 1 or more eddy jet mixers, though 1 is most usual.
Mixing: Theory and Equipment

68. Mixing: Theory and Equipment
Jet mixer
The tank contents are pumped through the top of the mixer to the primary nozzles. Then, after passing through the common suction chamber, the 12 streams of fluid are discharged into the tank through the secondary nozzles.
As the pressurized fluid flows through the primary nozzle and into the chamber, it creates a suction because of its high velocity-typically 6-10 m/s for low-shear mixing and m/s for high shear.
This suction draws fluid from the tank into the chamber, where the large velocity difference causes intense mixing.
The mixed fluid is then expelled from the jet through the secondary nozzle. This forms a cone that entrains the surrounding liquid, and a plume that spreads horizontally before rising to the surface. The plume imparts most of its energy to the fluid in its path, causing circulation and mixing throughout the tank. Mixing in the tank is less intense than in the suction chamber.
Mixing: Theory and Equipment

69. Applications of Jet mixer
Jet mixers tend to be used in situations that require turbulence, rapid approach to homogeneity, and high local shear rates.
Jet mixing is normally used for liquids and slurries having viscosities below 1,000 cP; a mechanical agitator is generally more efficient for higher-viscosity fluids. 
Mainly useful for processes of liquid blending.
e.g., neutralization or extraction.
Mixing: Theory and Equipment

70. Flow mixer or line mixer or pipe mixer
It may consist a baffled pipe or an empty chamber.
Liquids to be mixed are passed through the pipe/ chamber.
Mixing takes place through bulk transport in the direction of flow.
The power supplied to pump the liquid itself accomplishes mixing.
For effective mixing controlling the feed rate is essential.
Baffled pipe
If the input rate is difficult to control and fluctuations in the added proportions of the liquids are unavoidable, continuous mixing equipment of tank type is preferable, because hold-up of the liquids and back flow or recirculation is possible.
Mixing: Theory and Equipment

71. Applications of pipe line mixer
Used when large volume of liquids are to be mixed.
Used for continuous mixing.
Mixing: Theory and Equipment

72. Advantages of liquid mixing
Liquid mixing promotes heat transfer between liquid and a heating source. This step is essential in the crystallization of drug substances. Uniform heat transfer in the solution yields crystals of same size.
Liquid mixing is essential in the manufacture of number of dosageforms.
E.g.:
Suspensions
Emulsions
Solutions
Aerosols
Mixing: Theory and Equipment

73. Mixing of immiscible Liquids
Carried mainly in the manufacture of emulsions, and the equipment used for the preparation of an emulsion is known as emulsifier. Also known as homogenizer as it results in fine emulsion.
Fine emulsion is prepared in 2 stages.
In 1st stage coarse emulsion is prepared by using one of the following process:-
Wedge wood
Mechanical blender
Hand homogenizer
Porcelain mortar and pestle
Milk shake mixer
Propeller in a baffled tank
Some times the above equipment directly gives fine emulsion.
Otherwise coarse emulsion is subjected to homogenizer in the 2nd stage to get fine emulsion by using following process:-
Silverson emulsifier
Colloidal mill
Rapisonic homogenizer
Mixing: Theory and Equipment

74. Factors influencing selection of an emulsifier
Quantity of emulsion to be prepared: batch wise or continuous operation
Flow properties of liquids: Newtonian, plastic, pseudo plastic or dilatant.
Temperature maintenance: mixing will be effective at high temperatures provided the material is stable.
Desired rate of cooling: if elevated temperatures are applied
Mixing: Theory and Equipment

75. Mixing: Theory and Equipment
Silverson emulsifier
Colloidal mill
Rapisonic homogenizer
Mixing: Theory and Equipment

76. Silverson mixer -Emulsifier
Principle:
It produces intense shearing forces and turbulence by use of high speed rotors.
Circulation of material takes place through the head by the suction produced in the inlet at the bottom of the head.
Circulation of the material ensures rapid breakdown of the dispersed liquid into smaller globules.
It consists of long supporting columns and a central portion. Central portion consists of a shaft which is connected to motor at one end and other to the head.
Head carries turbine blades.
Blades are surrounded by a mesh, which is further enclosed by a cover having openings.
Mixing: Theory and Equipment

77. Mixing: Theory and Equipment
Uses:
Used for the preparation of emulsions and creams of fine particle size.
Advantages:
Silver son mixer is available in different sizes to handle the liquids ranging from a few milli liters 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.
Mixing: Theory and Equipment

78. Mixing: Theory and Equipment
Colloid mill
16/08/2012
Mixing: Theory and Equipment

79. Ultrasonic Emulsifiers – Rapisonic homogenizer
Principle:
When a liquid is subjected to ultrasonic vibrations alternate regions of compression and rarefaction are produced in the liquid.
Cavities are formed in the regions of rarefaction which subsequently collapse in the regions of compression. Which results great forces for emulsification.
Construction:
It consists of a pump driven by a motor. It is connected to inlet tube and an out let tube.
Head consists of a flat jet for liquid inlet. Facing the jet, a thin blade is present which vibrates at its natural frequency.
Mixing: Theory and Equipment

80. Mixing: Theory and Equipment
Advantages of rapisonic emulsifier:
Can be used for batch process (by placing it in a tank) or for continuous process (by placing it in a pipeline).
It has the capacity to produce dispersed globules of one micron size.
As this method is highly efficient to decrease globule size, reduced concentration of emulgents is sufficient.
Its capacity of mixing liquids ranges from liters per minute.
It is suitable for thermolabile substances since heat is not generated during mixing.
Disadvantages of rapisonic emulsifier:
It is useful only for low viscous liquids.
Mixing: Theory and Equipment

81. Mixing: Theory and Equipment
Mixing of semisolids
Semi solids dosageforms include ointments, pastes, creams, jellies, etc., while mixing such dosageforms , the material must be brought to the agitator or the agitator must move the material throughout the mixer.
The mixing action include combination of low speed shear, smearing, wiping, folding, stretching and compressing.
A large amount of mechanical energy is applied to the material by moving parts. Sometimes a part of the supplied energy appears as heat.
The forces required for efficient mixing are high and consumption of power is also high. Hence the equipment must be rugged constructed to tolerate these forces.
Some semisolids exhibit dilatant property 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.
Mixing: Theory and Equipment

82. Classification of equipment
Agitator mixers:
e.g.:- Sigma mixers and Planetary mixer.
Shear mixers:
e.g.:- Triple roller mill and Colloidal mill.
Selection of mixing equipment for semi solids
Physical properties of the materials – density viscosity and miscibility.
Economic considerations regarding processing – time required for mixing and power consumption.
The cost of equipment and its maintenance.
Mixing: Theory and Equipment

83. Mixing: Theory and Equipment
Triple roller mill
Principle:- High shear , which causes crushing of aggregates, particles and also distributes the drug uniformly throughout the semi solid base.
It consists of 3 parallel rollers of equal diameters made up of stainless steel.
These are mounted on rigid frame work horizontally.
The gap between the first 2 rollers is more than that of the gap between the last two.
A hopper is placed in between the first two rollers.
A scrapper is attached to the last roller.
First roller rotates at lower speed compared to the 2nd similarly 2nd roller speed is less than the 3rd roller.
Mixing: Theory and Equipment

84. Advantages of triple roller mill
From the small to the large batch - Three roll mills are ideally suited for processing the smallest and also very large quantities.
Excellent temperature control - Three roll mills enable excellent control of the product temperature, since the product is processed as a thin film on the roller. This way, the product can be warmed or cooled off depending on your requirements.
Avoid contamination - Through the selection of materials for the rollers and scraper knives, which are available in a broad spectrum of chrome-plated steel, aluminium oxide, zirconium oxide, and silicon carbide, it is possible to avoid product contamination due to metal abrasion.
Extremely uniform dispersion is obtained.
low material loss.
easy cleaning.
Mixing: Theory and Equipment

85. Mixing: Theory and Equipment
Pharmaceutical engineering by CVS Subrahmanyam
Mixing: Theory and Equipment

86. Mixing: Theory and Equipment
Any Query.?
Mixing: Theory and Equipment