MIXING Flashcards
Unit operation that aims to treat two or more
components, initially in an unmixed or partially
mixed state, so that each unit (particle, molecule,
etc) of the components lies as nearly as possible in
contact with a unit of each of the other
components
Mixing
an ideal situation when each particle
lay adjacent to a particle of the other component
Perfect mix
where the probability of selecting
a particular type of particle is the same at all
positions in the mix, and is equal to the proportion
of such particles in the total mix
Random mix
Importance of Mixing
- Ensure an even distribution of the active
components - Ensure an even appearance
- Ensure that the dosage form releases the
drug at the correct site and at the desired
rate
Types of Mixtures
- Positive mixtures
- Negative mixtures
- Neutral mixtures
Formed from materials such as gases or miscible liquids which mix spontaneously
and irreversibly by diffusion, and tend to approach a perfect mix
positive mixing
No input of energy required
positive mixing
T/F: Materials that mix by positive mixing
present no problems during product
manufacture
T
Components will tend to separate out
Negative Mixtures
Energy must be continuously input to keep
the components adequately dispersed
Negative Mixtures
Generally more difficult to form and
maintain and require a higher degree of
mixing efficiency than do positive mixtures
Negative Mixtures
Static behavior
Neutral Mixtures
components have to
tendency to mix spontaneously or segregate
spontaneously once work has been input to
mix them
Neutral Mixtures
Mixed powders, pastes and ointments
Neutral Mixtures
Mathematical Treatment of the
Mixing Process
- Standard deviation
- Percentage coefficient of variation
Mechanisms of Mixing and Demixing for Powders
convection mixing, shear mixing
and diffusion mixing
Mechanisms of Mixing and Demixing for Liquids
bulk transport, turbulent mixing
and molecular diffusion
T/F: Powder segregation is a.k.a demixing
T
Transfer of relatively large groups of particles from one part of the powder bed to another, as might occur when a mixer blade or paddle moves
through the mix
Convection Mixing
Contributes mainly to the macroscopic mixing of
powder mixtures and tends to produce a large
degree of mixing fairly quickly
Convection Mixing
T/F: Convection mixing does not, however, occur within the group
of particles moving together as a unit,
T
In order to achieve a random mix in convection mixing, an ____________ is required
extended mixing
time
Occurs when a layer of material moves or flows
over another layer.
Shear Mixing
This might be due to the
removal of a mass by convective mixing creating an unstable shear/slip plane, which causes the powder bed to collapse
Shear Mixing
Shear Mixing occurs in high shear mixers or _____________
tumbling mixers
where the action of the mixer induces velocity
gradients within the powder bed and hence
shearing of one layer over another
high shear mixers or tumbling mixers
Movement of individual particles through
the voids created due to gravit
Diffusive Mixing
Potential to produce random mix, generally
results in a low rate of mixing
Diffusive Mixing
Analogous to the convective mixing of
powders
Bulk Transport
Involves the movement of a relatively large
amount of material from one position in the
mix to another, eg due to a mixer paddle
Bulk Transport
Arises from the haphazard movement of molecules
Turbulent Mixing
this means that induced turbulence is highly effective
mechanism for mixing
Constant changes in speed and direction of movement
Within a turbulent fluid there are, however, small
groups of molecules moving together as a unit,
referred as
Eddies
alone may therefore leave small
unmixed areas within the eddies and in areas near the
container surface which will exhibit streamlined flow
Turbulent mixing
Analogous to diffusive mixing in powder
Molecular Diffusion
Occur with miscible fluids wherever a
concentration gradient exits and will
eventually produce a well-mixed product
Molecular Diffusion
Opposite effect of mixing
Powder Segregation
Components tend to separate out
Powder Segregation
Will cause an increase in content variation in
samples taken from the mix and may cause a batch
to fail a uniformity of content test
Powder Segregation
Particle size effects, particle density effects,
particle shape effects
Powder Segregation
Ordered mixes can reduce or
prevent segregation, it occurs if
- Carrier particles vary in size
- There is competition for the active sites on
the carrier particle - There are insufficient carrier particles
Practical Considerations
- Geometric dilution
- Volume of powder in the mixer
- Mixer should produce the mixing mechanism
appropriate for the formulation - Mixer design – dust tight, easily cleaned, product can
be fully discharged - Checking of the mixing process at different time to
determine the most appropriate mixing time - Mixers should be earthed to dissipate the static
charge and the process should be carried out at a RH
> approx. 40%
Mixers should be earthed to dissipate the static
charge and the process should be carried out at a RH
________________
> approx. 40%
Mixer design should be
dust tight, easily cleaned, product can
be fully discharged
Blenders
Tumbling Mixers
Commonly used for the mixing/blending of granules or free
flowing powders but poor for cohesive or poorly flowing
powders
Tumbling Mixers
blending lubricants,
glidants or external disintegrants with granules prior to tableting
Tumbling Mixers
Can also be used to produce ordered mixe
Tumbling Mixers
Double cone mixers, twin-shell mixers, cube mixers. Y-cone
mixers and drum mixers
Tumbling Mixers
Mounted so that they can be rotated about an axis. When
operated at the correct speed, the tumbling action indicated is
achieved
Tumbling Mixers
Common to use Intermediate bulk containers (IBCs) both as the
mixer bowl and to either feed the hopper of a tablet or capsule
machine or as the hopper itself
Tumbling Mixers
Can both mix and granulate a product,
thereby removing the need to transfer the
product between pieces of equipment and so
reducing the opportunity for segregation to
occur
High Speed Mixer-Granulators
Drying of granules or the coating of
multiparticulates
Fluidized Bed Mixers
Used to mix powders prior to granulation in
the same bowl
Fluidized Bed Mixers
Agitator Mixers depends on the motion of a blade or paddle
through the product, and hence the main mixing
mechanism is ___________
convection
Mixing is achieved by the rotation of helical
blades in a hemispherical trough. D
Agitator Mixers
Dead spots are
difficult to eliminate in this type of mixer and the
shearing action caused by the movement of the
blades may be insufficient to break up drug
aggregates
Agitator Mixers
mix poorly
flowing material and is less likely to cause
segregation than a tumbling mixer
Agitator Mixers
Mobile liquids with ________ are easily mixed
with each other
low viscosity
Solid particles are readily suspended in ________, although the particles are likely to settle
rapidly when mixing is discontinued
mobile
liquids
more difficult to stir and mix
but they reduce the sedimentation rate of
suspended particles
Viscous liquids
Equipments used in mixing of mixcible liquids and suspensions
propeller mixer, turbine
mixers, In line Mixers
Common arrangement for medium scale fluid mixing, which may be
clamped to the edge of a vessel
Propeller mixers
has angled blades, which cause the fluid to circulate in both
an axial and radial direction
Propeller mixers
(Propeller Mixers) An off centre mounting discourages the formation of a _________, which
may occur when the stirrer is mounted _______.
vortex; centrally
(Propeller Mixers) forms when
the centrifugal force imparted to the liquid by the propeller blades
causes it to back up around the sides of the vessel and create a
depression at the shaft.
Vortex
(Propeller Mixers) the speed of rotation is ___________, air may be
sucked into the fluid by formation of a vortex, this can cause frothing
and possible oxidation
increased
(Propeller Mixers) Another method of suppressing the vortex is to fit _________ into
the vessel
vertical baffles
(Propeller Mixers) Ratio of the diameter of a propeller stirrer to that of the vessel is ___________, operates at speeds of 1-20 rps
1:10 –
1:20
Used for more viscous fluids
Turbine Mixers
(Turbine Mixers) Impeller has _____ flat blades surrounded by perforated inner
and outer diffuser rings.
4
(Turbine Mixers) draws the
liquid into the mixer head and forces the liquid through the
perforations with considerable radial velocity, sufficient to
overcome the viscous drag of the bulk of the fluid
rotating impeller
absence of an axial component, but a different
head with the perforations pointing upwards can be fitted if
this is desired (Turbine Mixers)
Drawback
As the liquids is forced through the small orifices of the
diffuser rings at high velocity__________ are
produced (Turbine Mixers)
large shear forces
Will not cope with liquids of very high viscosity, as the
material will not be drawn into the mixer head
Turbine Mixers
s an alternative to mixing fluids in batches
in vessels, mobile miscible components
may be fed through an inline mixer
designed to create turbulence in a flowing
fluid stream
Inline Mixers
Continuous mixing process is needed
Inline Mixers
Problems that arise during the mixing of semi-
solids (ointments & pastes) stem from the fact,
that, unlike powders and liquids, semisolids will
_____________
not flow easily
T/F: Material that finds its ways to dead spots will
remain there.
T
In mixing semisolids, suitable mixers must
have rotating elements with narrow clearances
between themselves and the mixing vessel wall
and they must produce a ___________, as diffusion and convection cannot occur
high degree of shear
mixing
Mixer used in mixing semisolids
planetary mixers, sigma blade
mixer
Commonly found in domestic kitchen and larger machines
which operate on the same principle are used in industry
Planetary Mixers
Mixing blade is set off centre and is carried on a rotating
arm.
Planetary Mixers
travels round the circumference of the mixing bowl
while simultaneously rotating around its own axis
Planetary Mixers
This is
therefore a double rotation similar to that of a spinning
planet rotating around the sun
Planetary Mixers
A small clearance between the vessel and the paddle gives
shear, but scraping down several times is necessary to mix
the contents well as some materials are forced to the top of
the bowl
Planetary Mixers
Used to mix powders, particularly if a wet mass
granulation is required
Planetary Mixers
Robust mixer that will deal with stiff pastes and
ointments and depends for its action on the close
intermeshing of the 2 blades which resembles the Greek
letter Sigma in shape
Sigma Blade mixer
(sigma blade mixers) he clearance between the blades and the mixing trough
is kept _________ by the shape greek letter Sigma
small
T/F: It is very difficult using primary mixers to completely
disperse powder particles in a semisolid base so that they
are invisible to the eye. (Sigma Blade mixer)
T
The mix is usually subjected to
the further action of __________, so as to rub
out these particles by the intense shear generated by
rollers or cones set with very small clearance between
them. (Sigma Blade mixer)
roller mill or colloid mill
