Pharmaceutical engineering Mixing ,types , factors affecting

Mixing

1. Mixing By Prof. Deepali D.Pawar Assistant Professor R. G. Sapkal College of Pharmacy, Nashik 1

2. Contents ▶ Objectives, applications & factors affecting mixing, ▶ Difference between solid and liquid mixing, ▶ mechanism of solid mixing, liquids mixing and semisolids mixing. ▶ Principles, Construction, Working, uses, Merits and Demerits of- Propellers, Turbines, Paddles Double cone blender & Twin shell blender Ribbon blender Sigma blade mixer Planetary Mixers Silverson Emulsifier 2

3. Introduction ▶ An operation in which two or more components (in a separate or roughly mixed condition) are treated so that each particle lies as nearly as possible in contact with a particle of each of the other ingredients. Or ▶ The process that tends to result in a randomization of dissimilar particles within a system ▶ Ideal mix is the one in which the particle of one substance lies nearly adjacent as possible to a particle of other material 3

4. Mixing 4

5. ▶ Mixing is divided into two categories Homogenous mixing Solid- Solid Liquid- Iiquid Gas- Gas Heterogenous Mixing Solid- Liquid Solid- Gas Liquid gas 5

6. Objectives of Mixing ▶ To ensue uniformity of composition between mixed ingredients ▶ To enhance the Physical or chemical reactions ▶ To produce 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. In pharmaceutical practice the degree of mixing must commonly be of high order as many such mixtures are dilutions of a potent substances, and correct dosage must be ensured. ▶ To produce physical change: Here mixing may aim at producing a change that is physical as clear from chemical, e.g. solution of a soluble substance. In such cases, a lower efficiency of mixing with often be acceptable because mixing merely accelerates a process that could occur by diffusion, without agitation. ▶ To produce dispersion: This includes dispersion of two immiscible liquids to form an emulsion or dispersion of a solid in a liquid to give a suspension or paste. Usually good mixing is required to ensure stability. ▶ To promote chemical Reaction: Mixing usually encourage (and control at the same time) a chemical reaction. So ensuring uniform product, e.g. products where accurate adjustment to pH is required and the degree of mixing will depend on the process. 6

7. Types of Mixture Positive Mixture Negative Mixture Neutral Mixture 7

8. Positive Mixture ▶ Mixing of soluble solid or liquid in another liquid 8

9. Negative Mixture ▶ Mixing of insoluble solid or liquid in another liquid 9

10. Neutral Mixture ▶ The components of these mixture do not mix spontaneously with each other but do not separate once mixed. ▶ Eg. Paste or Ointments 10

11. Application of Mixing ▶ Mixing of powder in varying proportions prior to granulation and tableting ▶ Dry mixing of the material for direct compression in tablet ▶ Dry blending of powder in capsule and compound powder (insufflation). ▶ Blending of powders in cosmetics in the preparation of face powder, tooth powders. ▶ Dissolution of soluble solids in viscous liquid for dispensing in soft capsule and in preparation of syrup. ▶ Mixing of two immiscible liquid for preparation of emulsion. 11

12. factors affecting mixing, ▶ Nature of surface ▶ Particle size ▶ Particle shape ▶ Particle charge ▶ Density of particle ▶ Proportion of material 12

13. Difference between solid and liquid mixing 13

14. Mechanism of Mixing A. Solid Mixing Convection Mixing Shear Mixing Diffusive Mixing B. Liquid Mixing Bulk Transport Turbulant mixig Laminar Mixing c. Semisolid Mixing 1. Molecular Mixing 14

15. Convection Mixing ▶ Convective mixing is the mixing of solid particles in which groups of particles are moved from one position to another. ▶ Convective mixing is the action of mixing two groups of solid particles so that they are dispersed in each other. ▶ Movement of relatively large portion of a material being mixed from one location to another in a system ▶ Does not result in efficient mixing ▶ It is made effective by means of paddle, blade or shuffling of system in three dimensions 15

16. Diffusive Mixing ▶ Diffusive mixing is caused by the random motion of particles. Generally, the attainable rate of homogenization (mixing) is greatest with convective mixing and least with diffusive mixing, whereas the degree of local homogenization attainable is greatest with diffusive mixing and least with convective mixing. ▶ Diffusive mechanism occurs by random movement of particle within a powder bed and causes them to change their relative position in relation to one another. ▶ When a powder bed is forced to move, it will dilate (The volume occupied by the bed will increase). This occurs because the powder particles become less tightly packed and there is an increase in the air spaces or voids between them. So there is the potential for the powder particles to pass through the void spaces created under gravitational forces (in tumbling mixer) or by forced movement (in fluidized bed). Mixing of individual particles is referred to as diffusive mixing 16

17. Shear Mixing ▶ This type of mixing occurs when a layer of material flows over another layer resulting in the layers moving at different speeds and therefore mixing at the layer interface. ▶ Occurs when; The removal of mass by convective mixing creates an unstable shear/slip plane which causes the powder bed to collapse ▶ The action of the mixer induces velocity gradients within the powder bed 58 17

18. Bulk Transport ▶ The movement of relatively large portion of thematerial being mixed from one location in thesystem to another. 18

19. Turbulent mixing ▶ Turbulent mixing is the result of turbulent fluid flow (Characterized by random fluctuation of the fluid velocity at any given point in the system) ▶ The churning flow characteristics of turbulence results in constantly changing velocities, so the fluid has different instantaneous velocities at different locations at the same instant in time ▶ Such temporal and spatial velocity differences produces randomization of fluid particles that’s why turbulent mixing is highly effective mixing mechanism ▶ Turbulent flow can be conveniently visualized as a composite of eddies 19

20. Laminar Mixing ▶ Flow dominated by viscosity forces is called laminar flow and is characterized by smooth and parallel line motion of the fluid ▶ pplicable for viscous liquid or laminar liquids ▶ When two dissimilar liquids are mixed through laminar flow, the shear that is generated stretches the interface between them ▶ In this mechanism, layers fold back upon themselves. Thus the number of layers increases. So, the mixing involves reduction of fluid layer thickness by producing folding effect. The applied shear stresses between the interfaces of the 2 dissimilar liquids to be mixed. 20

21. Molecular Mixing ▶ The mixing result from the diffusion of molecules caused by thermal motion is referred to as molecular diffusion. This mechanism occurs at molecular level. ▶ This type of mixing occurs whenever there is a concentration gradient (According to Fick’s law). 21

22. IMPELLER ▶ Impellers are mixing devices that provide a definite flow pattern in liquid during mixing, moving at various speeds. ▶ Liquids are mixed usually by impellers, which produce shear forces for inducing the necessary flow pattern in the mixing container. CLASSIFICATION ▶ Impeller exists in different forms. 1. Propeller 2. Turbine 3. Paddles PROPELLER MIXER CONSTRUCTION ▶ Consist of angle blades attached at the end of the shaft, rotated by means of motor. ▶ Any number of blades may be used but three blades design is most common. 22

23. Shaft Motor 23

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25. ▶ Propeller is quiet small as compare to size of the vessel (Ratio of diameter between propeller and container is 1:20) but its operational speed (usually 8000rpm) compensate for the size and produce efficient mixing in case of low viscosity fluids 33 WORKING ▶ The material to be mixed is taken in a vessel and the propeller bearing shaft is inserted. ▶ The angle blades of the propeller cause circulation of the liquid in both axial and radial direction ensuring good bulk transport but low shearing force. ▶ The propeller may be installed in a number of ways. ▶ The centrally mounted vertical propeller is however not considered good as it produces vertex. ▶ Specially used for liquid liquid mixing 25

26. ADVANTAGES ▶ Used when high mixing capacity is required. ▶ Effective for liquids which have maximum viscosity of 2.0 pascals.sec or slurries up to 10% solids of fine mesh size. ▶ Effective gas- liquid dispersion is possible at laboratory scale. Example ▶ Multivitamin elixirs, Disinfectant solutions are prepared using propellers 35 DISADVANTAGES OF PROPELLERS ▶ Propellers are not normally effective with liquids of viscosity greater than 5 pascal- second, such as glycerin castor oil, etc ▶ The centrally mounted vertical propeller produces vertex. 26

27. VORTEX ▶ Vertex is a powerful circular moving mass of water or wind that can draw object into its hollow which may result in air entrapped and bubbles formation. ▶ If a low viscosity liquid is stirred in an un-baffled tank by an axially mounted agitator, tangential flow follows a circular path around the shaft & a swirling flow pattern is developed. ▶ HOW IS IT FORMED? ▶ In an un-baffled tank, a vortex is produced due to the centrifugal force on the rotating liquid. This creates a swirling motion in the liquid & the surface tends to go upward near the vessel rim & downward near the shaft. So a V- shaped surface is formed which is the vortex. 27

28. REASONS ▶ If the shaft is placed symmetrically in the tank. ▶ If the blades of the turbines are arranged perpendicular to the central shaft. ▶ At high impeller speeds ▶ Unbaffled tank PREVENTION OF VORTEX FORMATION 1) Impeller should be in any one of the following positions that can avoid symmetry such as; off central, inclined , side entering, etc., ▶ and should be deep in the liquid 28

29. 2) Baffled containers should be used. In such case impeller can be mounted vertically at the center 29

30. 3) PULL PUSH PROPELLER ▶ Two or more propeller of opposite angles or pitch are mounted on the same shaft so that the rotary effects are in opposite direction, cancel each other effect (so will not produce circulatory flow and no vertex will be there). ▶ The bottom impeller is placed about one impeller diameter above the bottom of the tank. It creates zone of high turbulence 30

31. TURBINE MIXER CONSTRUCTION ▶ A turbine consists of a circular disc impeller to which a number of short vertical blades are attached. Blades may be straight or curved. ▶ The blades are surrounded by perforated inner and outer diffusing rings ▶ The diameter of the turbine ranges from 30- 50% of the diameter of the vessel WORKING ▶ Used in similar manner as that of impeller, however it is rotated at somewhat small speed than impeller (50- 200 rpm). ▶ 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). 31

32. ▶ Diffuser ring increase the shear forces and liquid passes through the perforations reducing rotational swirling and vortexing. ADVANTAGES ▶ Turbines give greater shearing forces than propellers though 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. 32

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34. PADDLE MIXERS ▶ Paddles are agitator consisting of usually flat blades attached to a vertical shaft and normally operated at low speed (100- rpm). ▶ The blades have a larger surface area In relation to the tank in which they rotate, so they can be used effectively. ▶ Primarily paddle mixer produce tangential flow and somewhat radial flow but no axial action unless blades are pitched. ▶ Paddles for more viscous fluids have a number of blades which are shaped in such a way to fit closely to the surface of vessel (Avoiding dead spots and deposited solids) ▶ At very low speeds it gives mild agitation in un-baffled tank but as for high speeds baffles are necessary to avoid swirling and vortexing. 34

35. TYPES OF PADDLE MIXERS Simple paddle mixer Planetary motion mixer : (Small paddle rotating on its own axis but travel also in a circular Path round the mixing vessel. It is used for more viscos fluids) Gate mixer: (It is a simple paddle, but is very large in diameter) Stationary paddle mixer : (It is used for mixing of solid with viscos liquid. Sigma plate mixer is its improved form) USES OF PADDLES Paddles are used in the manufacture of; Antacid suspensions Agar and pectin related purgatives Antidiarrheal mixtures such as bismuth- kaolin. 48 35

36. 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. 36

37. Double cone Blender Principle it is based on hthe principle of convection of solid particlein which material moves from one place to another Construction 37

38. ▶ Cone blenders are useful for mixing dry powder and granules. ▶ These are made out of stainless steel. ▶ All welding are done by Argon Arc Process. This is totally mirror polished from inside & outside. Unit is mounted on Mild Steel / Stainless Steel stand fitted with ball bearings. ▶ The driving arrangement consists of a motor through a reduction gear box, S.S. baffles, are provided inside the blender. Safety railing along with limit switch and platform (optional) are supplied generally for bigger models 38

39. Advantages & Disadvantages ▶ Not expensive ▶ Easy to handle and perform ▶ Electricity required ▶ Material loss may happened 39

40. APPLICATIONS ▶ Dry powder to powder mixing for tablets and capsules ▶ formulations. ▶ Dry granules sub lots mixing to increase the batch size at ▶ bulk lubrication stage of tablet granules. ▶ Dry powder to wet mixing 40

41. Twin Shell Blender 41

42. Construction ▶ Loaded 50-60% of total volume through shell hatches. ▶ Desired speed or rpm is set Rotation of blender Mixing occurs as the material free falls randomly inside the vessel Ordered mixing by mechanical means Collected 42

43. Advantages & Disadvantages Advantages ▶ V cone blender without baffle Larg Capacity Easy Handling Minimum Maintanance ▶ V cone blender without baffle wet and dry Mixing high shearing force serial dilution is not needed Disdavantages ▶ V cone blender without baffle High headspace for installation Not suitable for fine particle sysytem serial dilution required ▶ V cone blender with baffle size reduction cleaning problem sealing problem 43

44. Uses ▶ Fragile granules can be blended ▶ Used in pharmaceutical cosmetics and chemical industry ▶ Dry powder blending 44

45. Ribbon blender Principle It is based on the principle of Convection of solid material (Tumbling, shear, Attrition) 45

46. Construction and Operation ▶ U- shaped horizontal trough ▶ A specially designed Double Helical Ribbon Agitator rotating within. ▶ It provides a triple mixing action ensuring fast, efficient blending. ▶ A drive system comprised of a motor, gearbox, and couplings. ▶ They are generally powered by 10 HP to 15 HP motor for 1000 kg of product mass to be blended. ▶ The specific power range from 3 to 12 kW/m3 depending on the products to be blended. ▶ The area where the shaft exits the container is provided with a sealing arrangement ▶ The charging of material is generally through nozzles or feed- hoppers ▶ The inlet cover also provides maintenance and cleaning access to the inside of the blender 46

47. ▶ An external jacket can also be provided for heating or cooling of product material ▶ The materials to be blended are loaded into the blender, typically filling it to between 40 and 70 percent of the total volume of the container. ▶ Up to the level of the outer ribbon’s tip. ▶ It is designed to operate at a peripheral speed (also known as tip speed) of approximately 100 metres / minute ▶ A spray pipe for adding liquids can be mounted above the ribbons. ▶ For materials that tend to form agglomerates, high speed choppers can be provided for disintegration of the agglomerates. ▶ The motion of the ribbons near the vessel walls can in result in “pinch" points, or regions of high shear and compression, which may damage materials and cause attrition. In some case this can also lead to friction and heat generation resulting in product degradation 47

48. Working ▶ The outer ribbons of the agitator move the material from the ends to the center while the inner ribbons move the material from the center to ends. Radial movement is achieved because of the rotational motion of the ribbons. ▶ The difference in the peripheral speeds of the outer and inner ribbons results in axial movement of the material along the horizontal axis of the blender. ▶ As a result of the radial and the counter- current axial movement, homogenous blending is achieved in short time. ▶ Blending is achieved within 15 to 20 minutes of start- up with a 90 to 95 percent or better homogeneity. ▶ The particle size and its bulk density have the strongest influence on the mixing efficiency of the ribbon blender. ▶ Ingredients with similar particle size and bulk densities tend to mix faster as compared to ingredients with variation in these attributes. 48

49. CONT. ▶ After blending, the material is discharged from a discharge valve located at the bottom of the trough. ▶ The discharge valves can be slide- gate, butterfly, flush bottom, spherical , etc…… ▶ The operation of the valves can be manual or pneumatically actuated. ▶ In a ribbon blender the material is discharged by rotation of the ribbon agitator. ▶ It is difficult to achieve 100% discharge in the ribbon blender. ▶ Also, higher clearances between the external periphery of the outer ribbon and the container can result in unmixed spots at the trough bottom and can lead to discharge problems. 49

50. Advantages & Disadvantages ▶ Sticy material can steak to blade ▶ electricity required ▶ Speed can be increase ▶ Easy to install ▶ less space required 50

51. Applications ▶ Ribbon blenders can be designed to operate in both batch and continuous modes. ▶ Batch type blenders can be built up to capacities of 50 m3. ▶ The ribbon blender’s versatility for blending solids combined with it ability to perform heating, cooling, coating, and other processes make it a very popular blender. 51

52. Applications The following are the applications of the Ribbon Blender: Blending large volumes of dry solids. Dry powder to wet phase mixing. Mixing of bulk drugs, chemicals, and cosmetic powders. Dry Blending of capsule formulations. Lubrication of dry granules in large quantity. Heating, cooling, and drying of materials. Coating solid particles with small amounts of liquids to produce formulations 52

53. Sigma blade mixer ▶ The sigma blade mixer is a commonly used mixer for high viscosity materials. ▶ One of the most popular used for mixing and kneading of high viscosity materials. ▶ It belongs to the family of double arm kneader mixers. PRINCIPLE ▶ The mechanism of mixing is shearing. ▶ The inter meshing of sigma shaped blades creates high shear and kneading actions. ▶ The mixing action is a combination of bulk movement, shearing, stretching, folding, dividing, and recombining as the material is pulled and squeezed against blades, saddle, and side walls. 53

54. CONSTRUCTION ▶ The design is mostly based on the curvature and concavity of the kneading blades. ▶ It consists of double trough shaped stationary bowl. ▶ Two sigma shaped blades are fitted horizontally in each trough of the bowl. These are connected to a fixed speed drive. ▶ The mixer is loaded from the top and unloaded by tilting the entire bowl by means of a rack and pinion drive. ▶ It consist of saddle shaped container made of either Mild Steel or Stainless Steel 304 or 316 with jacket of covering two side for heating or cooling application & dust free cover to get Vacuum if desired or normal cover. 54

55. ▶ The mixing elements (Blades) are of Sigma type Steel casted and duly finished two in number which contra rotate inward fitted at close or specified clearance with the container to give thorough and uniform mixing. ▶ There is a Gland pusher of Gun Metal Bush which ensure minimal friction and extend the life of mixing elements (Blades) Shaft. ▶ The complete Mixer is Mounted on Steel Fabricated stand of suitable strength to withstand the vibration and give noise free performance ▶ Specially used for liquid liquid mixing 55

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57. WORKING ▶ Different powders are introduced from the top of the trough. ▶ The body is covered because considerable dust may be involved during dry blending and granulating solution may evaporate during wet granulation. ▶ The kneading blades first squash the mass flat and then roll it on itself and squash once again. ▶ It tears the mass apart, and shear it in between the moving blades and the stationary surface walls. ▶ Through the fixed speed drive, the sigma blades are allowed to rotate. ▶ The blade move at different speeds. ▶ The effectiveness of mixing depends upon the kneader blade design, sometimes they are made very rugged, and of different shapes. ▶ The edges of the blades may be more serrated to give higher shredding action. 57

58. Applications of the Sigma Mixer ▶ Adhesives, Biscuit dough, Butyl rubber, Bakery, Carbon pastes, Ceramics, Chemicals, Chewing gum, Crayon and pencil lead. Explosives, Fiberglass resin dough's, Food and confectionery products, Gaskets and gland packing's, Grinding wheel preparations, Hot- Melts, Inks and pigment products , Marzipan, Mastics, Metal powders, preparations, Pencil erasers, Pharmaceuticals, Plastics, Moulding Sealing compounds, Silicone rubber, Soaps and detergents, Solid propellants, Sugar pastes, Viscous rubber solutions 58

59. ADVANTAGES & DISADVANTAGES ADVANTAGES ▶ Sigma blade mixer creates a minimum dead space during mixing ▶ Ideal for mixing, kneading, of highly viscous mass, sticky & dough like products ▶ Extruding ▶ These mixers and their variants (double arm kneader mixer extruders) are capable of handling material with viscosities as high as 10 million centipoises. DISADVANTAGES ▶ Sigma blade mixer works at a fixed speed ▶ The power consumption in double arm kneader mixer is very high compared to other types of mixers and can range from 45 to 75 kW/m3 of mix material. 59

60. Planetary Mixers 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. 60

61. 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. 61

62. Silverson 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. 62

63. 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. 63

64. THANK YOU 64