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

Positive mixtures Negative mixtures Neutral mixtures

MIXING Flashcards by Kim Grace

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

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an ideal situation when each particle
lay adjacent to a particle of the other component

Perfect mix

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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

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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

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Types of Mixtures

Positive mixtures
Negative mixtures
Neutral mixtures

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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

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No input of energy required

positive mixing

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T/F: Materials that mix by positive mixing
present no problems during product
manufacture

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Components will tend to separate out

Negative Mixtures

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Energy must be continuously input to keep
the components adequately dispersed

Negative Mixtures

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Generally more difficult to form and
maintain and require a higher degree of
mixing efficiency than do positive mixtures

Negative Mixtures

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Static behavior

Neutral Mixtures

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components have to
tendency to mix spontaneously or segregate
spontaneously once work has been input to
mix them

Neutral Mixtures

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Mixed powders, pastes and ointments

Neutral Mixtures

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Mathematical Treatment of the
Mixing Process

Standard deviation
Percentage coefficient of variation

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Mechanisms of Mixing and Demixing for Powders

convection mixing, shear mixing
and diffusion mixing

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Mechanisms of Mixing and Demixing for Liquids

bulk transport, turbulent mixing
and molecular diffusion

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T/F: Powder segregation is a.k.a demixing

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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

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Contributes mainly to the macroscopic mixing of
powder mixtures and tends to produce a large
degree of mixing fairly quickly

Convection Mixing

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T/F: Convection mixing does not, however, occur within the group
of particles moving together as a unit,

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In order to achieve a random mix in convection mixing, an ____________ is required

extended mixing
time

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Occurs when a layer of material moves or flows
over another layer.

Shear Mixing

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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

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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.

(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.

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)

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