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
i ii
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
5