IntroductionMixing is one of the most common pharmaceutical operations. It is difficult to find a pharmaceutical product in which mixing is not done at one stage or the other during its manufacturing. 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 and in any possible ratio of two or more components. Mixing of a gas with another gas, mixing of miscible low viscosity liquids and mixing of a highly soluble solid with a low viscosity liquid to effect dissolution are relatively simple as compared to the mixing of gases with liquids, mixing of liquids of high viscosity though miscible, mixing of two immiscible liquids such as aqueous and oily s olutions to form emulsions, mixing of solids with liquids when the proportion of solids is high and mixing of solids with solids, specialized equipments are required for these operations. Some of the examples of large scale mixing practiced in pharmacy are:

Mixing of powders in varying proportions prior to granulation or tabletting

Dry mixing of the materials for direct compression in tablets

Dry blending of powders in capsules and compound powders (insufflations).

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.

Depending on the flow p roperties of materials, solids are divided into two types: 1. Cohesive materials - These are characterized by their resistance to flow through openings for e.g. wet clay. 2. Noncohesive materials These materials flow readily such as grain, dry sand, pl astic chips etc. Mixing of cohesive materials is more difficult due to formation of aggregates and lumps. Wet mixing is encountered in pharmacy as an individual operation or as a subsequent step after dry blending. In pharmaceutical practice, solid-solid, solid-liquid and liquid -liquid mixing are generally batch operations where the batch may be as large as one ton.

Objectives of mixing Mixing can be done for the following reasons: To ensure that there is uniformity of composition between the mixed ingredients which may be determined by taking samples from the bulk material and analyzing them, which should represent overall composition of the mixture. To initiate or to enhance the physical or chemical reactions e .g. diffusion, dissolution etc. Generally mixing is carried out to obtain following type of products: When two or more than two miscible liquids are mixed together, this results in to a solution known as true solution. When two immiscible liquids are mixed in the presence of an emulsifying agent, an emulsion is produced. When a solid is dissolved in a vehicle, a solution is obtained When an insoluble solid is mixed with a vehicle, a suspension is obtained. When a solid or liquid is mixed with a semi solid base, an ointment or a suppository is produced. When two or more than two solid substances are mixed together, a powder is obtained which when filled into capsule shell is known as capsules and when compressed under heavy pressure is called tablet.

7\SHVRI0L[WXUHVMixtures may be classified as follows: 1. Positive mixtures 2. Negative mixtures 3. Neutral mixtures I. Positive Mixtures These types of mixtures are formed when two or more than two gases or miscible liquids are mixed together by means of diffusion process. In this case no energy is required provided the time allowed for solution formation is sufficient. These types of mat erials do not create any problem in mixing. II. Negative Mixtures These types of mixtures are formed when insoluble solids are mixed with a vehicle to form a suspension or when two immiscible liquids are mixed to form an emulsion. These mixtures are more difficult to prepare and require a higher degree of mixing with external force as there is tendency of the components of these mixtures separate out unless they are continuously stirred. III. Neutral Mixtures Many pharmaceutical products such as pastes, ointments and mixed powders are the examples of neutral mixtures. They are static in their behavior. The components of such products do not have any tendency to mix spontaneously but once mixed, they do not separate out easily. Many variations occur within the above explained groups owing to the different physical properties of the components of the mixture like viscosity which might change during mixing, the relative densities of the components, particle size, ease of wetting of solids, surface tension o f liquids, while other factors such as the proportions of the components and the required order of mixing may exert an influence.

Mechanism of MixingIn all type of mixers, mixing is achieved by applying one or more of the following mechanisms: Convective mixing During convective mixing transfer of groups of particles in bulk take place from one part of powder bed to another. Convective mixing is referred to as macromixing. Shear mixing During shear mixing, shear forces are created within the mass of the material by using agitator arm or a blast of air. Diffusive mixing During this mixing, the materials are tilted so that the gravitational forces cause the upper layers to slip and diffusion of individual particles take place over newly developed surfaces. Diffusion is also sometimes referred to as micromixing.

Rate of MixingMixing is the process of achieving uniform randomness of the mixed components, which on subdivision to individual doses contain the correct proportions of each component wh ich depends on the amount of mixing done. In the early stages of mixing, the rate of mixing is very fast because the mixing particles change their path of circulation quickly and find themselves in different environment whereas at the end of the process rate of mixing reaches to almost zero because the particles do not find different environment.

Theory of mixingA significant aspect in mixing is to define when a particular batch is mixed. This depends on the method used for examining the samples and its accuracy, the number and location of the s amples and the desired properties of the mixture. Diverse criteria like electrical conductivity of the samples, specific gravity of the samples, the amount of a key constituent in the samples, the rate of solution of a soluble solid in the samples etc. hav e been used to determine the uniformity of a mixed batch. Some of the recent methods of analysis include X-ray fluorescence, emission spectroscopy, flame spectrometry, radioactive tracer methods etc. But these criteria are not all equivalent. For example, if two aqueous solutions or two oily materials or two powders of two specific gravity are mixed, mixing is said to be accomplished when the specific gravity of the mixture is uniform at all points. But if the specific gravity is determined using a hydrometer, the mixture may appear uniform. But if the more accurate pycnometer is employed, the mixture may appear non-uniform. Still the mixture appearing to be uniform by the hydrometer test may be adequate for the user. Therefore the question whether a particular batch is mixed or not is not absolute but only relative. As for the location of the samples, these points could be fixed arbitrary points decided on experience or points where mixing is known to be poorest. Some other criteria such as the method of sampling, location, size, number of samples, method of sample analysis and fraction of batch removed for sampling are important. The theory of mixing should also be able to predict the time in which a given batch is adequately mixed in a given vessel and how much power is used for mixing. Not much is known about the time factor which is largely a function of the characteristics and proportion of the materials being mixed, the size and shape of the container involved, criteria used to determine when mixing is complete and many other factors.

In a two-component mixture, perfect or ideal mixing is said to have been achieved when each particle of one material lies as nearly as possible to a particle of another material. In practical degree of mixing is defined by its1/2

standard deviation which is equal to (xy/N) where x and y are the proportions of the components and N is the number of particle in the sample taken. Mixing of pharmaceutical powders is continued until the amount of active drug that is required in a dose is within 3 standard deviation of that found by assay in a representative number of sample doses. For this N is to be made large by milling the ingredients to a sufficient degree of fineness.

I. Liquid mixing Liquid mixing may be divided into following two subgroups: 1. Mixing of liquids and liquids a) Mixing of two miscible liquids b) Mixing of two immiscible liquids

2. Mixing of liquids and solids a) Mixing of liquids and soluble solids b) Mixing of liquids and insoluble solids 1. (a) Mixing of two miscible liquids (homogeneous mixtures e.g. solutions) mixing of two miscible liquids is quite easy and occur by diffusion. Such type of mixing does not create any problem. Simple shaking or stirring is enough but if the liquids are not readily miscible or if they have v ery different viscosities then electric stirrer may be used. Sometimes turbulence may be created in the liquids to be mixed. Turbulence is a function of velocity gradient between two adjacent layers of a liquid. Thus if a rapidly moving stream of liquid i s in contact with a nearly stationary liquid, there will be high velocity gradient at the boundary which results in tearing off portions of the faster moving stream and sending it off to the slower moving areas as vortexes or eddies. These eddies persists for some time and ultimately dissipate themselves as heat. This results also in drawing in part of the slow moving liquid into a high velocity liquid because of differences in static pressures created as in an ejector. Most of the mixing equipments are designed on the basis of providing high local velocities but directing them in such a manner that they will ultimately carry their own turbulence or the turbulence of the eddies they create, throughout the mass to be mixed 1.(b) Mixing of two immiscible liquids (heterogenous mixtures e.g. emulsions) two immiscible liquids are mixed to effect transfer of a dissolved substance from one liquid to another an eg. of such type of mixing is the extraction of penicillin in the acid form from aqueous solution into t he organic solvent amyl acetate, to promote a chemical reaction after transfer of a component, to allow transfer of heat from one liquid to the other or to prepare emulsion. When two immiscible liquids are mixed together in the presence of an emulsifying agent an emulsion is produced. For the production of a stable emulsion, the mixing must be very efficient i.e. continuous without ceasing because the components tend to separate out if continuo us work is not applied on them.

Mixing occurs in two stages: (1) Localized mixing in which shear is applied to the particles of the liquid (2) A general movement sufficient to take all the particles of the materials through the shearing zone so as to produce a uniform product. On small scale, for the preparation of emulsions, a pestle and mortar is quite suitable. Here, shear forces are produced between the flat head of the pestle and the flat bottom of the mortar whereas a general movement is produced by continuous movement of the pestle along the sides of the mor tar by which the sticking material to the sides is returned to the bottom of the mortar. Generally emulsions are prepared in two stages (i) primary emulsion (ii) secondary emulsion. In the primary stage the two immiscible liquids are triturated with an emulsifying agent to get a primary emulsion, which is further diluted by adding more of vehicle. After the preparation of an emulsion which is coarse in nature may be passed through a homogenizer to get a homogeneous emulsion of desired particle size.

2. (a) Mixing of liquids and soluble solids (homogeneous mixtures e.g. solutions)- in this case soluble solids are dissolved in a suitable liquid by means of stirring. It is a physical change i.e. a soluble solid is converted to a solution. 2.(b) Mixing of liquids and insoluble solids (heterogeneous mixtures e.g. suspensions) when insoluble solids are mixed with a liquid a suspension is produced which is an unstable system. The ingredients of a suspension separate out when allowed to stand for sometime. Thus a suspending agent is required to produce a stable suspension. On small scale, suspensions may be prepared in a pestle and mortar. Table 1 shows classification of mixing equipments. Table 1: Classification of mixing equipmentsS.No. 1 Type of mixing Liquid-liquid mixing Name of the mixer Uses Used in the preparation of emulsions, antacid suspensions, mixtures such as anti-diarrhoeal bismuth-kaolin mixtures etc. Rapisonic homogenizer is particulary used in the mixing of immiscible liquids i.e. preparation of emulsions.

Shaker mixers

Propeller mixers

Paddle mixers

Turbine mixers

Sonic and ultrasonic devices such as Rapisonic

homogenizer

2

Solid-solid mixing

Used for the mixing of dry powders.

Agitator mixers

Tumbling mixers

Double-cone mixers

V-blenders

3

Semi-solid mixing

Agitator mixers like sigma mixers and planetary mixers

These mixers are used for wet granulation process in the manufacture of tablets, in the production of ointments. Sigma mixers can also be used for solid-solid mixing.

Shear mixers like colloidal mills and triple roller mills

If the aim of the mixing process is simply to produce a blend of two liquids that are readily miscible or to form a solution of a solid in liquid then flow alone may be sufficient but flow is unlikely to prove adequate when the aim of mixing is to produce an emulsion from two immiscible liquids , shear forces being essential. iThe wide range of mixing equipment available commercially reflects the enormous variety of mixing duties required in the chemical, paint, Food, and pharmaceutical industries. Some of these duties are listed below:y y

Blending of miscible liquids; Contacting of immiscible liquids, e.g. in solvent extraction processes; Emulsification processes to produce stable products;

y y y y

Suspending coarse solids in low-viscosity liquids; Dispersing fine solids in high-viscosity liquids; Dispersing gas in liquids, e.g. fermentation processes; Contacting gas/solid/liquid in catalytic chemical reactions.

It is clear that no single item of mixing machinery will be able to carry out such a range of duties efficiently, i.e. withlow capital and operating cost. Thus a number of distinct types of mixer have been developed over the years. e.g.y y y y y y y y

Mechanically agitated vessels; Jet mixers; In-line static mixers; In-line dynamic mixers; Dispersion mills; Valve homogenizers; Ultrasonic homogenizers; Extruders.

The above list is not exhaustive and within each of the above types there is still a wide range of possible designs. Very little has been done in the way of standardization of equipment and no design codes are available. In the following sections the main mechanical features of each type of equipment are described and the range of operating duty is discussed. This is done in a largely qualitative way and it is hoped that this will set the scene for the detailed quantitative treatments of liquid mixing processes which are presented in the subsequent chapters.

0HFKDQLFDOO\DJLWDWHGYHVVHOV A typical arrangement for a mechanically-agitated vessel is shown in here. This diagram serves to illustrate the overall configuration and the main features of the component items are discussed below.

9HVVHOV These are often vertically mounted cylindrical tanks which typically will be filled to a depth equal to about one tank diameter when running full. However, in some gas/liquid contacting systems a liquid depth up to about three tank diameters is used with multiple impellers on the shaft. Vessel diameters can range from 0.1 m for small bench units up to 10 m or more in l arge

industrial installations. The base of the tanks may be flat, dished or conical, depending upon factors such as ease of emptying or solids suspension. If a deep cone is used at the base of a cylindrical tank care must be taken to ensure adequate mixing in the cone. This can be achieved by lowering the position of the impeller but there may be a danger of inadequate mixing near the liquid surface. In such cases it may be necessary to use two impellers on the shaft to ensure good mixing in the lower and upper regions of the vessel. In some cases. to prevent deposition of solids on the tank bottom. a specially contoured base has been proposed'. Such modifications should only be introduced when supported by sound physical reasoning. In the design of mixer settler units for solvent-extraction purposes it has been common practice to use square tanks because of their low cost for large-capacity applications and because of the ease of combination with the settler. Some tanks are mounted horizontally, particularly for batch handling of viscous pastes and doughs using ribbon impellers and Z-blade mixers. etc. In such units the working volume is often relatively small and the mixing blades are massive in construction.

%DIIOHV To prevent gross vortexing behavior when low- viscosity liquids are agitated in a vertical cylindrical tank with a centrally mounted impeller. Barriers are often fitted to the walls of the vessel. Typically four barnes will be used. each having a width equal to about one-tenth of the tank diameter. In some cases the barnes are mounted flush with the wall. Although occasionally a small clearance is left between the baffle and the wall. Barnes are generally not required with high- viscosity liquids where gross vortexing is not a problem.

,PSHOOHUV Propellers, Turbines, paddles , Anchors, helical ribbons. And helical screws are usually mounted on a central vertical shaft inside a vertical cylindrical tank and their range of application depends to a great extent upon liquid viscosity.

Thus propellers, Turbines, and paddles are generally used with relatively low viscosity systems and operate at high rotational speeds. A typical tip speed for a turbine is in the region or 3 m/s with a propeller being somewhat faster and the paddle slower. These impellers are classed as remote clearance impellers having diameters in the range 1/4 to 2//3 or the tank diameter.

3URSHOOHU PL[HUV A device comprising a rotating shaft with propeller blades attached, used for mixingrelatively low viscosity dispersions (thicker solutions) and maintaining contents in suspension. Propeller mixers are the most widely used form of mixers for liquids of low viscosity. It rotates at a very high speed i.e., up to 8000 r.p.m. due to which mixing is done in a short time. They are much smaller in diameter than paddle and turbine mixers.

Uses of propeller mixers: Propellers are used when high mixing capacity is needed. These are effective in handling liquids having a viscosity of about 2.0 Pascals. second. 9 Disadvantages: Propellers are not effective with liquids of viscosity greater than 5 pascals.second for example, glycerin and castor oil.turbine mixers (figure 1-b) consist of a circular disc impeller to which a number of short, straight or curved blades are attached. These mixers differ from propellers in that they are rotated at a lower speed than propellers and the ratio of the impeller and container diameter is also low. The former produces greater shear forces than propellers therefore they are used for mixing liquids of high viscosity and has a special application in the preparation of emulsions. Baffles are often used to prevent vortexes.

7XUELQHPL[HUV

figure:Turbine mixer in a baffled tank

Propellers are used for blending water-thin materials even in large tanks and can handle liquids having a maximum viscosity of about 2,000 cp and slurries up to 10 % solids of fine mesh size. They can also be used for intensive agitation and for emulsifying jobs up to about 1,000 gallons. In contrast turbines are highly efficient. They can bring rapid blending of low viscosity materials of large volumes, produce intense dispersion type agitation in large volumes and can bring about efficient dispersion in multi-liquid phase systems. They can handle slurries containing up to a maximum viscosity of 7, 00,000 cps. They can also handle fibrous slurries containing about 5 % of the dispersion volume.

Uses of turbine mixers: Turbines are effective for high viscous solutions with a wide range of viscosities up to 7,oo pascal.seconds. Advantage: Turbines give greater shearing forces than propellers and thus they are more suitable for preparation of emulsions.

0DWHULDOVRI&RQVWUXFWLRQDQG6DQLWDU\5HTXLUHPHQWVStainless steel alloys are widely used to fabricate impellers, providing excellent resistance to corrosion and therefore minimizing contamination of the materials being processed. The concern for purity in the food, dairy, beverage and pharmaceutical industries is reflected in the demand for smooth surfaces, particularly the surfaces that contact the fluids being used. Surface smoothness can significantly reduce localized corrosion processes and the stainless ste els can be smoothed by either mechanical or chemical treatments or by electropolishing. Surface scale and discoloration that appears after heat treatments can be removed by chemical treatments. For high purity requirements electropolishing not only offers the advantage of being versatile, but provides a very smooth surface that is readily passivated. Teflon impellers are commercially available today and stainless steel shafts can easily be clad with a layer of the fluoropolymer. The hydrophobic nature of the surfaces results in less build-up of material on the impeller and shaft. Several types of stainless steel impellers can be coated with Teflon if necessary. Mixing impellers for biotech applications often are 316Lss, welded to the shaft, polished to 20RA, and then passivated and electropolished. Impellers should also be self draining and capable of being cleaned via CIP and SIP. Biopharm mixing impellers would typically be fabricated rather than cast to provide for a pit free polished finish. Material test reports on the 316Lss or material of construction are often required. In addition to the sanitary nature of the mixing impeller, other options are available from various manufacturers. Ringuard or shrouds for the impeller are used especially when mixing with bag liners in the drum. Mixing prop stabilizer or stabilizing rings are used to enhance the mechanical stability of the shaft/impeller system and help with fill up and draw down.

Careful consideration should be taken to assure the impeller provides the right flow, shear, mixing action while also being mechanically sound for mixer critical speed and bending moments.

7KH'HVLJQDQG'LPHQVLRQVRIWKH0L[LQJ9HVVHO The geometry of the mixing vessel, in terms of the aspect ratio and the shape of the bottom, should not be overlooked. Dish-bottomed vessels are preferred, although flat-bottomed or shallow cone ( 15) can be used without particular problems. The ratio of the depth of fluid to the diameter of the vessel (the aspect ratio) should be unity or close to unity. The position of the impeller within the process fluid can also affect performance. Incorrect location of either single or multiple impellers can result in staged flow patterns and non-uniform distribution of added materials. Mixing vessels are often fitted with baffles, these being stationary elements located at or near the walls. Baffles tend to inhibit liquid swirl and therefore minimize tangential flow, allowing axial flow patterns to develop. The dimensions of the mixing vessel must be considered when selecting the size and shape of the impeller. The ratio of the diameter of the impeller to that of the mixing vessel should range from 0.2 to 0.5, i.e., 0.2 D/T 0.5, where D is the diameter of the impeller and T is that of the vessel. The distance from the impeller to the bottom of the vessel (the clearance, C) affects the power draw and pumping efficiency of the mixer. For optimum performance the ratio C/T should range from 0.1 to 0.3, although hydrofoils operate with C/T approximate 0.5. ly Impeller positioning in the tank should be considered as there are a number of ways to orient the shaft/impeller to achieve the mixing results. Number of impellers is also a consideration depending on mixing volumes.

+RZWR6SHFLI\WKH0L[LQJ,PSHOOHUSome of the information your mixing vendor will require: What is your desired mixing results. What are you mixing. Volume you are mixing. Tank dimensions. High and low liquid levels. Mixture Viscosity, SG or Density, Solids %.. Impeller diameter, shaft size for bore. Mixer speed range. HP available. How secure impeller to shaft. Materials of construction and documentation required. Surface finish Polish. Coatings, electropolish, EP. Impeller style desired. A general conversation on what is desired and all the process and mechanical information for the mixing application will help a vendor provide assistance in selecting the right impeller for the job.ii

-HWPL[HUV

Mixing in a vessel can be achieved for low-viscosity applications by the use ofa submerged nozzle from which a high-velocity jet or liquid emerges. A pump is used to withdraw part of the liquid from the vessel and recycle it via the nozzle to the vessel. The momentum transferred from the high-velocity jet to the liquid in the vessel causes the mixing action and circulation within the tank (see Figure 7.6). For blending in large tanks. Several nozzles may be used. Similarly, mixing in vessels and lagoons can be achieved by gas injection with no mechanical agitation. In the simplest case bubble columns using a perforated plate distribution cause a swarm of bubbles to rise through the liquid and this gives an agitation effect to the liquid phase. if liquid circulation is important then air-lift devices, often coupled with a draft tube, can be used, Again many geometrical variations are possible.1

1

Mixing in the Process Inudtries by N.Harnby,M.F.Edwards and A.W.Nienow.

MIXING OF SOLIDSThe mixing of particulate system differs from those other systems in three important ways: 1. There is no particulate motion equivalent to the molecular diffusion of gases and liquids. The rate at which randomization of the constitute particles occurs is entirely dependent on the flow characteristics or handling pattern externally imposed on the particles. There is no relative movement in the particles without any energy input to the mixture. 2. Although the molecules of a single -phase liquids system may differ, and may diffuse at different rates, ultimately achieve a random distribution within the confines of the system. Particulate and granular components do not usually have the constant properties of molecular species and can differ widely in physical characteristics. Thus a mixing motion which depends on identical particulate properties is unlikely to achieve its objective. More commonly such a mixer would produce a grading or segregation of particles according to such characteristics as size,density,resilience etc. 3. The ultimate element of the particulate mixture is several degrees of magnitude larger than the ultimate molecular elements of liquid mixture. In the practical terms this means that sample withdrawn from a randomized particulate mixture will have a coarser texture or poorer mixture quality than would the equivalent samples taken from gaseous or liquid mixture. The industrial implications of these differences should be considered very carefully. Particles will change their relative positions only when subjected to motion. Once movements begins, the particles may segregate or randomized depending on both the types of movements imposed on the system and on the physical characteristics of the constituents . A major influence on the mechanism of mixing within a powder is the flow characteristics of that powder. (REF: Mixing in the process industries by N.Hamby,M.F.Edward,A.W.Nienow)

Particle size: Particle size and particle distribution are important since they largely determine the magnitude of forces,gravitational and inertial,that can cause interparticulate movements relative to surfaces forces which resist such motion.lachmen.variatins in particles size can lead to segregation also,since smaller particles can fall through the voids between the larger particles. There will be a critical particle size that can just be retained in the mixed condition, which will depend upon the packing. when the bed of particles is disturbed, dilation occurs and the larger size of particles to slip through the voids ,leading to segregation. 2 (ref:Mixing,pg no 204 tutorial PHARM ACY by cooper and guns) Forces acting in multiparticulate solids: Forces that operate at a particulate level during the mixing process are essentially of two types: 1. Those that tend to result in movement of two adjacent particles of or groups of particles relative to each other and 2. Those that tend to hold neighboring particles in fixed relative position. Mixing mechanism: It has been generally accepted that solids mixing proceeds by a combination of one or more mechanism. 1. Convective mixing: This mechanism may be regarded as analogous to bulk transport .depending on the type of mixer employed, connective mixing can occur by an inversion of the powder bed, by means of blades or paddles, by means of revolving screw, or by any other method of mo ving a relatively large mass of material from one part of the powder bed to another. 2. Shear mixing As a result of forces within the particulates mass, slip planes are set up. Depending on the flow characteristics of the powder, these can occur singly or in such a way as to give rise to laminar flow. When shear occurs between regions of different composition and parallel to their interface, it reduces the scale of segregation by thinning the dissimilar layers. Shear occurring in a direction normal to the interface of such layers is also effective since it too reduce the scale of segregation. 3. Diffusive mixing: Mixing by diffusion is said to occur when random motion of particles within a powder bed causes them to change position relative to one another. Su ch an exchange of positions by single particles results in a reduction of the intensity of segregation. Diffusive mixing occurs at the interfaces of dissimilar regions that are undergoing shear and therefore results from shear mixing .it is also produce by agitation. MIXING EQUIPMENTS 1.Tumbler mixers: The popular twin shell blender is of these types and takes the form of a cylinder that has been cut in half, at approximately a 45 degree angle with its long axis and then rejoined to form a V shape. This i s rotated so that the material is alternately collected in the bottom of the V is inverted. This is quite effective2

Mixing,pg no 204 tutorial PHARMACY by cooper and guns

because the bulk transport and shear which occur in tumbling mixers generally, they are accentuated by this design s. a bar contain blades that rotate in a direction opposite to that of the twin shell often is used to improve agitation of the power bed, and may be replaced by a hollow tube for the injection of liquids. The efficiency of tumbling mixers is high depended on speed of rotation. R otation that is too slow the t does not produce the desire intense tumbling or cascading motion, nor does it generate rapid shear rates. On the other hand, rotation that is too rapid tends to produce centrifugal force sufficient to hold the powder to the sides of the mixture and thereby reduces efficiency. The optimum rate of rotation depends on the size and shape of the tumbler and also the on the size and shape of the tumbler and also the type of material being mixed, but is commonly in the range of 30 to 100 rpm. 3Tumbling mixers are good for fre-flowing powders/granules but poor for cohesive/poorly flowing powders because the shear forces generated are usually insufficient to break up any aggregates. Applications: 1. 1.Blending of lubricants,glidants or external disintegrants with granulesprior to tableting 4

2.Ribbon blenders: The ribbon blender is one of the most common general purpose mixers,as it is capable of effectively performing a wide range of mixing process including liquid,solid and liquid solid blending.common industrial applications of these blenders include mixing the powder components of pharmaceutical tablets,blending oils and shortening into dry ingredients. The motion of the ribbon blades near the v essels walls can result in pinch points,regions of high shear and compression which may damage fragile materials or cause attrition.the capacity of ribbon,which must clear the top of the powder bed is order to mix the entire bed.as is true for many convect ive blenders.the intensity of shear can result in healing that can adversely affect the quality of the product. Colloid Mill The colloid mill is useful for milling, dispersing, homogenizing and breaking down of agglomerates in the manufacture of food pastes, emulsions, coatings, ointments, creams, pulps, grease, etc. The main function of the colloid mill is to ensure a breakdown of agglomerates or in the case of emulsions to produce droplets of fine size around 1 micron. The material to be processed is fed by gravity to the hopper or pumped so as to pass between the rotor and stator elements where it is subjected to high shearing and hydraulic forces. Material is discharged through a hopper whereby it can be recirculated for a second pass. For materials having higher solid and fibre contents conical grooved discs are preferred. Sometimes cooling and heating arrangements are also provided in theses mills3 4

The Theory and practice of industrial pharmacy. Leon Lachman Mixing Pharmaceutics by Aulton,s

depending on the type of material being processed. Rotational speed of the rotor varies from 3,000-20,000 r.p.m. with the spacing between the rotor and stator capable of very fine adjustment varying from 0.001 inch to 0.005 inch depending on the size of the equipment. Colloid mills require a flooded feed, the liquid being forced through the narrow clearance by centrifugal action and taking a spiral path. In these mills almost all the energy supplied is converted to heat and the shear forces can unduly increase the temperature of the product. Hence, mostcolloid mills are fitted with water jackets and it is also necessary to cool the material before and after passing through the mill.Figure

During operation of a standard ribbon blenders,two sets of helical ribbon blades transport materials in opposite directions,the outer ribbon will transport toward the ce ntre of the mixing vessel while the inner ribbon transport material towards the ends of the vessel.turbulent convective currents caused by these counter rotating elements act to blend the different components .ribbon blenders is often not completely discharged by gravity,requiring additional rotation to complete this process. 5

In the helical flight mixer powders are lifted by by a centrally located vertical screw and allowed to cascade to the bottom of the tank. (Ref:The Theory and practice of industrial pharmacy. Leon Lachman)

4.Nautamiser Consists of conical vessel tited at the base with a rotating screw which is fastened to the end of a rotating arm at the upper end.the screw conveys the materials to near the top when it cascades back into mass.the mixer thus combines convective mixing(as the material is raised by the helical conveyor)and shear and diffusive mixing(as the material cascades downwards) 6

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http://nsdl.niscair.res.in/bitstream/123456789/751/1/Revised+mixing.pdf http://www.wmprocess.com/impellers-for-mixing-processes/#

Handbook of industrial mixing: science and practice, Volume 1By Edward L. Paul, Victor A. Atiemo -Obeng, Suzanne M. Kresta 6 Mixing Pharmaceutics by Aulton,s

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