Mixing of powders

Mixing
Importance:
1.
2.
3.

Ensure an even distribution of the active

component(s)
Ensure an even appearance of the Drug Formulation
Ensure that the DF releases the drug at the correct
site and at the desired rate

The majority of pharmaceutical products consist of

several ingredients, and thus mixing will be required
during the manufacturing process.

Mixing may be defined as a unit operation that aims to

treat two or more components, initially in an unmixed or
partially mixed, so that each unit of the components lie as
nearly as possible in contact with a unit of each of the
other components. If this is achieved, it produces a
perfect mix.

Complete
segregation

Perfect mix

Random
mix

However, this is practically impossible, and what we

usually get is a random mix.
The degree of mixing depends on the product being
manufactured and the objective of the mixing operation.
e.g. if a small amount of a potent drug is being mixed in a
powder, then the degree of mixing must be high.

Particle distribution in a
representative random mix
containing ~12% active
ingredient

When the particles number in the

scale of scrutiny is 25, the number
of active ingredient particles

Types of mixtures

Positive mixtures: formed from materials such as gases or

miscible liquids which mix spontaneously and irreversibly b
diffusion, and tend to approach a perfect mix. There is no
input energy if the available time is unlimited. However
energy will shorten the time.
Negative mixtures: components will tend to separate out.
This may occur quickly (low viscous suspensions), and it
may occur slowly (emulsions).
Neutral mixtures: static in behavior (the components have
no tendency to mix spontaneously or segregate
spontaneously,
spontaneously such
as mixed powders.

Mechanisms of mixing

The powder particles need to move relative to each other.

There are three main mechanisms by which powder mixing
occurs:
Convection: when there is a transfer of relatively large
group of particles from one part of the powder bed to
another ( when a mixer blade moves through the mix)
Shear: when a layer of material moves/flow over another
layer.
Diffusion: where particles fill the voids created during the
flow of powder bed.

Segregation:
Particle size effect: higher difference in the particle size
can lead to Segregation.
Particle density effect (gravity)
Particle shape: spherical particles segregate more easily
than non spherical particles.

Mixing equipment

The ideal mixer should produce a complete blend rapidly

with as gentle as possible a mixing action to avoid
product damage.
It should be cleaned and discharged easily,
be dust-tight and
require low maintenance and
low power consumption
mixers should be earthed to dissipate the static charge
on particles.

Mixing equipment
1- Tumbling mixers / blenders
Applications:
Used for mixing / blending of granules or free-flowing
powders.

Double-Cone

V-shape

Powder mixing equipments

1- Tumbling mixers/blenders

In tumbling mixers, rotation of the vessel imparts

movement to the materials by tilting the powder
until the angle of the surface exceeds the angle
of repose when the surface layers of the particles
go into a slide.
A common type of mixer consists of a container of
one of several geometrical forms, which is
mounted so that it can be rotated about an axis.

The drum type, cubical-shaped, double-cone and twin

shell blenders are all examples of this class of mixers.
Drum-type blenders with their axis of rotation horizontal
to the centre of the drum are used quite commonly.
Disadvantages: This suffers from poor cross flow along the
axis.
Remedy:- inclining the drum on its axis increases cross
flow and improves the mixing action.

Cubical and polyhedron shaped blenders with the rotating

axis set at various angles also are available.
Disadvantages:- In the polyhedron type blender, because
of their flat surface, the powder is subjected more to a
sliding than a rolling action which is not conducive to the
most efficient mixing.
Double cone blender provides a good cross flow with a
rolling rather a sliding motion.
Twin shell blender combines the efficiency of the inclined
drum-type with the intermixing that occurs when two
such mixers combine their flow.

Powder mixing equipments

2- High speed mixers/granulator

Powder mixing equipments

3- Agitator mixers

3- Agitator mixers
Planetary motion mixers are
effective, but special design
are to be preferred.
This type of mixers employs
a stationary container to hold
the material and brings
about mixing by means of
moving screws, paddles or
blades.
Use: Since the mixers do not depend
entirely on gravity as do the tumblers,
it is useful in mixing wet solids, sticky
pastes etc.

3- Agitator mixers
Ribbon blender

The ribbon blender consists of a

relatively long trough-like shell
with a hemispherical bottom. The
shell is fitted with a shaft on which
are mounted spiral ribbons,
paddles or helical screws, alone or
in combination. These mixing
blades produce a continuous
cutting and shuffling of the powder
by circulating the powder from end
to end of the trough as well as
rotationally. The shearing action
that develops between the moving
blade and the trough serves to
break down powder agglomerates.

3Agitator
mixers
Conical
orbital
screw mixer
(Nautamixer)
Conical orbital screw mixer consists
of a conical vessel fitted at the base
with a rotating screw, which is
fastened to the end of a rotating arm
at the upper end.
Working:
The mixer screw rotates at its own
axis and simultaneously moves in the
orbit at the periphery of the conical
container. It produces three mixing
currents:
(i) The mixer screw rotates to lift the
material to the top of the cone.

3- Agitator mixers
(ii)
Theorbital
rotating
arm
guides the whole
Conical
screw
mixer
(Nautamixer)
screw in a circular path along with the
periphery of the conical container so the
material is conveyed in a horizontal
manner.
(iii) The material drops off the screw to the
opposite side of the cone, and is lifted up
repeatedly.
Conical orbital
screw mixer (Nautamixer)
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).
Advantages: Nautamixer can be jacketed
and may be done under vacuum.
Nautamixer is used in mixing powder, wet
granulation. It may be used to mix plant

Factors affecting mixing efficiency by

tumbling mixers
1. Too high a rotation speed will cause the
material to be held on the mixer walls by
centrifugal force, and too low a speed will
generate insufficient bed expansion and little
shear mixing.
2. The addition of baffles or rotating bars will also
cause convective mixing, for example the
Vmixer with agitator bar.
3. Presence of significant difference in particle
size, as segregation is likely to occur.

Size of load
For a given mixer, there is always an optimum amount
(volume) of powder. For each type of mixers, the optimum
volume of powder varies.

It must be appreciated that there will always be some

variation in the composition of samples taken from
random mix. However, minimizing this variation to
acceptable levels is desirable.
Statistical assessment of mixing
process

Evaluation of the degree of mixing

The mixing index (M) compares the content standard
deviation of samples taken from a mix (SACT) with that of
samples from a full random mix (SR)

Random mix is achieved when SACT = SR