A Systematic and General Method for the Scale-Up of Granular Mixing Devices: The Mechanisms of Blending Act - Research Paper Example

Blending is the process that happens due to three important independent mechanisms which includes: convection, dispersion, and shear. Convection is the process by which huge groups of particles move in the direction of flow thereby causing product in vessel to rotate. On the other hand dispersion is the movement of particles as a result of collisions or antiparticle motion, generally orthogonal to the direction of flow. Shear divides the particles that are joined together because of cohesion and agglomeration and this requires high forces. Even though these definitions may be more important from a conceptual point of view and blending usually does not take place as merely self-determining, scalable mechanisms (Mueller-Wal, Fueg & Pieles, 2006). The mechanisms of blending act at the same time and are presented to others to see differently with scale dependence, making the scale up of difficult task in the process. When the powder is in the tumbling blender, mixing occurs as the result of particle motions in the thinpouring layer at the surface of the material, as what is remaining material rotates with the vessels as a rigidbody in addition all the fraternization and all the separation in the tumbling blender happens in the pouring region (Tensen and Patel, 1997). Tumbling blenders convey a very slight shear, but for an intensified bar (I-bar) or chopper blade when used it may convey high shear. High shear should be avoided at all cost because in same situation, it may be a disadvantage to the active ingredient hence does not give the quality results needed. In the absence of an I-bar, the little shear in the powder cascade, at the same time as with tensile normal stresses, which may lead to the separation of the adjacent particles. The loading of the powdered material into the vessel is caused by the Compressive normal stresses which are static and are due the total weight of the powder loaded into the vessel. In convective mixers, homogenization is determined by the flow field formed by the movement of the impeller (Brone and Muzzio, 2000). Normally, the total powder mass in the tumbling blender experiences a certain amount of shear at all times and the Shear levels are controlled completely by the speed at which the impeller that moves the flow. Shear always occurs due to the tensile stresses. However, it is much different from tumbling mixers, convective mixers which also works with compressive normal stresses which may be much higher than those which are caused by the powder weight hence their use as granulators. Generally, according to scale-up requirements, mixing of powdered materials processes may be grouped into two principles, free-flowing and blending (Adams and Baker, 1956). 2) What are the available blenders in pharmaceutical industries (V shape etc...?) Are the mostly used in the pharmaceutical, nutriceutical, chemical, and food industries normally use v-shell blenders, they are usually used to mix the dried powder and granules. It is composed of two v-shells which have different or same altitudes, which are of mechanical transmission, the materials inside the v- shells are usually set to move backward and forward, crossed over and rotate 360o to make the material to mix uniformly making the available several accomplish this task of blending. The following are the available blenders; V blender Lab v-blender Ribbon blender (VRB) 3-d blender (V3D) Cone blender (VFX) The most common ones are as follows: Firstly, the Ribbon Blender which is composed of a U-shaped horizontal trough and an agitator which is made up of the Inner and the outer helical ribbons which are at an angle of moving the material axially in the opposite directions, as Well as radially. The ribbons rotate at an estimated speed of 300 fpm. The same trough can be used for mixing for the blenders that require a gentler mixing action and the paddle agitator is replaced in the place of the ribbon assembly. A horizontal paddle blender provides lower shear and little heat development compared to the ribbon design which has less surface area at the periphery of the agitator. The liquid addition is finest accomplished through the spray nozzles which is used installed in the spraying bar and is normally located just on top of paddleagitator. The design of this blender is much efficient and cost-effective for dry mixing and is widely used for relative low margin-high volume e.g. the nutraceutical, beverages. This makes them to supplements because of its attractive price which makes it appealing. In the comparison between the vertical blender and the horizontal blender, the blending action of a Vertical Blender’s slow turning auger is far gentler than that of a horizontal blender which is much suitable for delicate applications. The augerscrew rotates on a conical vessel wall even though it turns and smoothly carries the material upward. As materials move to the upper most level of the batch, they cascade slowly back down in regions opposite themoving auger screw. Spray nozzles may also be installed in the vertical blender for liquidaddition purposes. The Tumble Blender is characterized by a rotating vessel which usually comes in a double-coneor V-shaped arrangement. The asymmetric vessels are considered to reduce the rate of blending times and improve its uniformity which is also available. Generally, tumble blenders works at a speed of 5- 25 revolutions per minute as the materials in the cascade intermix as the vessel rotates and mixing is at a very low-impact. The blending action is very gentle because of the intensifier bar, apiece which is usually comprehended on the tumble blenders as it benefits from high speed intensifier bar with one or more chopper blades and the intensifier bar breaks up agglomerates and also provides a means for liquid addition Sower provides vast variety of drums together with vessels and their mounting and fixing devices, for users from different industries like medicine or pharmaceuticals, food industries, resin synthesis, ink, and coating. Others comprised of unique shape and size, which contains a relatively high sanitary and sealing requirement. The standardizations and customizations or the reverse are available according to customers' specific requests. The quality are achieved by all kinds of certificates Sower as well as its deeply developed understanding and acceptability of the Chinese standards and ASME standards, which ensure the suitability of the tanks together with vessels produced. Automatic Feeding Systems & Filling Equipment Filling of the equipment is the most important unit of the blending machine and the level of feeding and filling equipment concerns the rate of production or production control level, efficacy, and output quality. Data base and network management aligns it and transmit the production data to management network of the factory resulting into backup, inquest , data printing functions and statistics, thereby enhancing the factory management level. The most appropriate and efficient way to optimize the yield rate and quality of the product is to enhance the process control precision and improve control mode of operation during the production and those are also the direct ways to reduce production cost of the enterprise and for the meantime to make the core competence of its products stronger. Work-Top Blenders During the operation the Work-top blenders are design in a way that they can be put on the on a counter top or table. Their components are; detachable glass, and a plastic or steel cover container with blades inside it. The container rests on a groove at the top of motor in the blender. When the buttons are pressed, the blades rotate at different speeds thus creating numerous effects in the mixing process. Such blenders are of various numerous highly preferred models exemplified with Hamilton and Oster (the on demand work-top blenders) as well as Sunbeam, GE, Sharp, and Black and Decker which are varied work-top blenders. Hand-Held Blenders (HHB) HHB are useful on surface or when held in hands. They are battery powered thus ideal for outdoor functions and since they are cylindrical they can be put in a container. Upon pressing the buttons, ingredients are mixed by the blades at the opposite end of the blender. Although they are portable, they are not as powerful as Work-top blenders and the best selling brand is Braun model. Speeds The models differ in speed and settings thus they make either thick or thin mixtures. Work-top for example have mores settings then HHB. Some work-top blenders posses not less than 16 settings unlike hand-held which have only three fundamental speeds. Size Hand-held blenders can mix various sizes of concoctions and drinks provided that their stem and blade fit in the opening of containers in which they are placed. However work-top blenders come with their own containers of different capacities with most having a capacity between 5 and 8 cups (Atkinson, et al., 1992). The different types of blenders include: Pride portable blender Mixer grinder Duc mounted type axial flow fan in test rig Air curtains Water heater Pump Tubular type Portable blender The Double Cone blender is an effective instrument for combining precipitates and particulates into a mixture of equal and consistent form. The constituents of the blender are made of steel of a specific prerequisite status to the liking of the client. For a homogenous mixture, the blender has to be filled to the two thirds mark. Various pharmacological, beautifying, and chemical products including some foodstuffs can be prepared using the double cone blender. The Octagonal Blender is a proficient and multipurpose appliance for combining and lubricating dry precipitates into a uniform mixture. For optimum operation, the blender should be operated at three quarters full. Since the blender is designed to prepare huge quantities of consignments, it’s essentially used in combining numerous sets of consignments into one single lot. Because of its octagonal form of the vessel and extremely low speed of operation, this blender gives the finest and most uniform mixture of combined and lubricated grains. The bulky vessel of the blender can be created as per the deliberate stipulations given by the customer to the customer’s satisfaction. It’s essentially used in the production of pharmacological, chemical, and beautifying products etc. Features Sturdy construction Flawless functionality Longer service life. Filling powder or filling material is filled in the capsule of the capsule machine. The machine has 300 holes used for manual adjustment of the capsule. After half filling of the capsule, excess filling material is washed away and the machine is closed and started. A complete cycle by the machine yields 300 capsules. DPI powder inhaler is available in pharmaceutical industries. The inhaler has sealed blisters with 30 individual doses of 2 to 20mg powder per dose filled. Harro Hofliger’s vacuum drum powder filling technology optimized is used in the inhaler to get highly consistent powder preparations at 360 doses per minute. An in-line advanced mass verification sensor placed directly at the dosing point regulates each fill weight. Powder in all blister pockets is checked by a camera inspection system. 12 filled and sealed blister strips are produced by the filling machine per minute after which they are loaded into the inhaler device (Begat, Morton & Staniforth, 2004). The DPI coupled to capsule powder medication is suitable for asthma patients but on doctor’s prescription (Category: Health & Medical | General Medical Supplies, Asthma Inhaler | Dry Powder Inhaler | Dpi Inhaler) Particle-bonding mechanisms: For granules to be made, links must be created between individual constituent parts so as to allow the parts to firmly stick to each other. These links have to be satisfactorily sturdy toavoid disintegration of the granules to dust precipitates in succeeding processes.There are five mechanisms through which particles link: Adhesion and cohesion forces in the immobileliquid films between individual primary powderparticles; Interfacial forces in mobile liquid films withinthe granules; The formation of solid bridges after solventevaporation; Attractive forces between solid particles; There are various mechanisms in which granule particles link; the few that will be debated here forth are those that are of relevance in pharmacological granule linkages. Adhesion and cohesion forces in immobile films: In a very thin immobile layer, formed when there is adequate fluid concentration in any dusty precipitate, there is, in effect, a reduction in interparticulate space and an elevation of interaction capacity amongst the grain individual particulates. The link forte amongst these particulates will be elevated because of this interaction, taking into account that the van der Waals forces of magnetism are directly proportionate to the diameter of each individual particulate diameter and is inversely proportionate to the distance of detachment, squared. Such circumstances are mostly encountered with adsorbed humidity and are responsible for the cohesion of mildly moist precipitates. When granules processed through wet granulation processes are desiccated, such films are encountered as remaining fluid. Their encounter does not, in any significant way, affect the final outcome of the granule strength. Inversely, pressures applied in dry method of granulation escalate the area of contact amongst the adsorption layers, thereby immensely reducing the interparticulate distance and finally contributing a major part in final outcome of granule strength. These thin immobile layers can also be produced by highly gelatinous elucidations of pastes and so the linkage strength will be of superior quality than those created by mobile films. Starch mucilage has mean times been put to use in pharmacological granulation to create this sort of film (Kawashima et al, 1998). Interfacial forces in mobile liquid films: For the duration of wet granulation processes, liquid added to precipitate combinations will be evenly and uniformly distributed as films around and amid the grain particles. Adequate liquid is the incorporated in excess so that no immobile layer is created but a mobile film is achieved. The recognizable states of liquid distribution amid grain particles are three .At low humidity levels, also known as the pendulumstate; the grain particles are attached together by lens-shaped liquid rings. Due to the surface tension forces of liquid/air interface and hydrostatic pressure in the liquid connection, adhesion is achieved. Capillary state is achieved when all air has been evacuated from ad mist the grain particles. At this point these particles are held together by capillary suction at the liquid/air interface now found solely on the grain particulate surface. The last recognizable state is the funicular state, which is an intermediate state between the pendulumand capillary states. At this intermediate state, moist grain particulate tensile strength is tripled. Though it may seem that the state of dust precipitate is reliant upon thehumidity content of wetted precipitate, it’s ideal to note that, that is not the case. The capillary state may also be achieved byreducing the distance of separation between the individual grain particles.( Johnson, Kendall& Roberts, 1997). During the wet granulation process, continued fraternization of the grain particulates and liquid originally in the pendulum state will invariably make the mixture mass denser. This inevitably reduces the pore volume capacity occupied by air, ultimately creating the funicular or capillary states without addition of more liquid to the mixture. An auxiliary state in addition to the previous three is the droplet state.This state is of significant value to the granulation processes throughspray drying of granulation suspensions. This in effect means that in this state, the droplet strength is reliant on the surface tension of the liquid in use. In wet granulation processes, these wet bridges are only transitory structures since all moist grain particles summarily will be dried. They are, nevertheless, a requirement for the development of solid bridges made by adhesive pastes existing in the liquid, or by ingredients that liquefy in the granulating solution (Price, Young, and Staniforth, 2002). Partial melting: This method of drying granules is not frequently employed especially with pharmacological supplies. It employs the use of pressure. In dry granulation these pressures cause melting of materials believed to be of low melting points. The melting is achieved when grain particulates under pressure touch and higher pressures are created. Crystallization occurs when the pressure is released; hence the grain particles are bound together. Hardening binders: This is the most common and frequently used mechanism in pharmacological wet granulation processes. This method employs the use of an adhesive paste which is incorporated into the granulating solvent. The work of the solvent liquid is to create a liquid bridge as deliberated above and the paste will toughen or set into gel on drying to create a solid bridge to hold fast the grain particles. Adhesive pastes such as polyvinylpyrolidone, the cellulose derived carboxymethylcellulose, or pregelatinized starch is recommended for use. Crystallization of dissolved substances: In this mechanism, an extra ingredient is incorporated into the dust particulate mixture that will act as a crystallizer once the process is initiated. The process is initiated by adding the granulating solvent into the powered ingredients as the wet process of granulation. The powderedingredients partly dissolve. In the drying processes, when the granules are being dried, crystallization occurs with the help of the extra ingredient incorporated into the powdered mixture as a hardening agent. An example of such an additive is lactose. The size of the crystals created after crystallization will be influenced by the rate at which the grain particles are dried. Drying time reduces as the particle size gets smaller. Henceforth ,it is essential that the a hardening ingredient doesn’t completely dissolve in the granulating liquid and recrystallize later during the drying processes this may produce undesirable effects in the solubility rate of the drug especially when the drug crystals formed are larger than those of the ingredients used to produce it. Attractive forces between solid particles: Electrostatic and Van der Waal forces) These are forces employed in the absence of liquid or solid bridges in pharmacological drug production system to operate between drug grain particles, effectively. They are namely electrostatic forces and van der Waals forces. Electrostatic forces trigger powder cohesion and preliminary materialization of agglomerates, however, they do not strengthen granule in any meaningful way. Conversely, the van der Waals forces with force of magnitude 4 times greater than the electrostatic forces considerably strengthen the granules during drying via the dry granulation processes. The extent of these forces will escalate as the distance between grain particulates is reduced (Lachiver et al, 2006). Granulation In the past, granulation process was done using a planetary mixer which is often used for wet massing of the powders; Powder mixing should be frequently done to separate operation using mixing equipment with some formulations, such as those containing two or three ingredients in approximately equal quantities, however, it may be possible to achieve a suitable mix in the planetary mixer without a separate stage. The mode of operation of the mixer is like that of a house hold mixer. The materials to be mixed are put inside the bowl part of the mixer. The granulating solvent is incorporated into the bowl and mixing is via the paddle of the mixer. The homogenous moist mass is then transferred to a granulator, such as an oscillating granulator. The rotor bars of the granulator oscillate and force the mass to pass through the sieve screen. The size of sieve screen determines the granule size. The mass should be adequately moist to form separate granules when sieved. If excess liquid is incorporated, strings of material will be formed and if the mix is too dry the mass will be filtered to powder and granules will not be formed. The granules are then put in a tray and relocated to a drying oven. However, the tray has the following disadvantages: 1. Dissolved material will migrate and move to the upper area of the bed of granules and the solvent is merely removed from the upper area of the bed on the tray. 2. Granules aggregate allowing bridge formation at granules contact points. After aggregation, disaggregation and remixing of the granules is done, dried and sieved. The granules can be dried using a fluidized-bed drier method. This method is much quicker and it reduces the problems of aggregation and intergranular solute migration, thereby reducing the need for a sieving stage after drying. Some of the traditional granulation methods are limiting in that they take long duration, the need for several pieces of equipment, and the high material losses that can be incurred because of the transfer stages (Kim, 2000). Advantages are not very sensitive to changes in the characteristics of the granule ingredients (e.g. surface area variations in different batches of an excipient), and the end-point of the massing process can often be determined by inspection. High-speed granulators High-speed mixer/granulators are widely used in the pharmaceutics. Its components are stainless steel mixing bowel with 3 blades. The bowel rotates along horizontal plane as the 3 choppers with blades rotate either along vertical or horizontal plane The unmixed powders are put into the bowl and are concocted by the rotating impeller (blades) for some minutes. Granulating liquid is then added via a port in the lid of the granulator while the impeller is rotating thus the granulating fluid is mixed with the powders in the process. The auxiliary chopper is regularly switched on when the moist mass is formed, as its function is mainly to break up the wet mass to produce a bed of granular material. When the suitable granule has been produced, the granular product is liquidated, passed through a wire mesh which degranulates any large aggregates into the bowl of a fluidized-bed drier. The advantage of the process include the mixing, massing and granulation which are all performed within a few minutes in the same piece of equipment. The process should be regulated carefully so that unusable granule is converted rapidly into usable granule over massed system. Thus it is often necessary to use anappropriate monitoring system to show the end of the granulation process, e.g. when a granule of the required properties has been attained. The process is also delicate to differences in raw materials, but it may be minimized by using a suitable end-point monitor. This is grounded on the bowl and overhead drive of the planetary mixer, but the single paddle is exchanged with the two mixing shafts in which one of these has three blades, which revolve in the horizontal plane at the lower part of the bowl, and the second one contains smaller blades which act as the chopper and revolve in the horizontal plane in the upper regions of the granulating mass hence the operation principles are similar (French, Edwards, and Niven, 1996). Fluidized-bed granulators Fluidized-bed granulators have a similar design and operation to fluidized-bed driers, i.e. fluidization of the powder particles is done in a steam and granulation fluid is squirted onto powder bed. Heated and filtered air is blown or sucked through the bed of unmixed powders to fluidize the particles and mix the powders; fluidization is a vital mixing process. Granulating fluid is squirted over the particles bed and the fluid causes adherence of the primary powder when they collide with droplets from spray. Exhaust filters prevent escape of materials from granulation chamber. Sufficient liquid is squirted so that granules of size of interest are produced after which the spray is turned off as fluidization of air continues. The heated fluidizing airstream then wets the granules. Fluidizedbed granulation has many advantages over conventional wet massing. All the granulation processes, which needed separate equipment in the conventional method, are achieved in one unit, saving labor costs, transfer losses, and time. Other advantage is that the procedure can be automatic once the conditions affecting the granulation have been optimized. The major differences in the granulation step associated with granulation for compaction: The amount of granulation fluid The importance of achieving a uniform dispersion of fluid The amount of fluid that is required to get the spheres of unvarying size and sphericity is expected to be greater than that for a similar tablet granulation. Poor-qualityproduct will produce a poor liquid dispersion and the uniform diameter from wet mass is produced by rod shaped particles by the extrusion. From end to end dies and shaped the wet mass is forced into the cylindrical particles with unvarying diameter. The extrudate particles are broken at same lengths in their own weight. Thus the extrudate should be more plastic to deform, however, very high plasticity can cause adherence of the extrudate particles when collected or rolled on spheronizer. The designs of extruder are divided in the following classes grounded in their feeding mechanisms; Screw-feed extruders Gravity-feed extruders Piston-feed extruders These are used for both development and production and at times they are only used for experimental development work as it is easy to add instrumentation. The primary extrusion process variables are: The feed rate of the wet mass The diameter of the die The length of the die The water content of the wet mass The properties of the extrudate, and hence the resulting spheres, are very dependent on the plasticity and cohesiveness of the wet mass. In general, an extrudable wet mass needs to be wetter than that appropriate for conventional granulation by wet massing. Spheronization: The function of the fourth step in the process is to round off the rods produced by extrusion into spherical particles. This is carried out in a relatively simple piece of apparatus .The working part consists of a bowl with fixed side walls and a rapidly rotating bottom plate or disc. The rounding of the extrudate into spheres is dependent on frictional forces generated by particle–particle and particle–equipment collisions. The bottom disc has a grooved surface to increase these forces. Two geometric patterns are generally used: • A cross-hatched pattern with grooves running at right-angles to one another • A radial pattern with grooves running radially from the center of the disc Conclusion A systematic and general method for the scale-up of granular mixingdevices is still far from within reach. Clearly, more research is needed to determine the recent hypotheses and to producenew styles to the problem. Still there are some simpleguiding principles that can help the practitioner wade through the scale-up process: Never change the changes in scale have not changed the dominant mixing mechanism in the blender e.g., convective to dispersive. And this usually occurs by introducing symmetry in the loading conditions. For free-flowing powders, the number of revolutions is a key parameter but rotation rates are largely unimportant and the key parameter is the number of revolution for the free flowing powder and the cohesive powders and mixing depends on the shear rate and the rotation is much important. Scale up test should be done by taking same samples to provide a correct explanation of the mixture state in the vessel. In addition, care should be taken when interpreting the samples you have. Know what the mixing index means and what your confidence levels are. A modest way to proliferation of the mixing rate is to decrease the fill level. 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Pharm. 198, 239–247 Atkinson, R.M. et al. (1962) Effect of particle size on Griseofulvin blood levels in Man. Nature 193, 588 Read More