Mixing and Homogenization, Mixing and homogenization of drugs, Important topic of pharmaceutics, Topic for pharma students

1. Mixing
&
Homogenization

2. Mixing is the most widely used operation in which two or
more than two substances are combined together. Perfect
mixing is that in which each particle of one material lies as
nearly adjacent as possible to a particle of the other
material.
The main objective of mixing may be:-
Simple physical mixing of material to form a uniform
mixture
To promote the chemical reaction to get uniform
products
Dispersion of solid in liquid to form suspension or
paste
Dispersion of two immiscible liquid to form an
emulsion

3. 1) Positive Mixtures: When two or more than two
miscible liquids are mixed or soluble solids is
dissolved in water , the mixture is called positive
mixtures.
2) Negative Mixtures: When two immiscible liquid are
mixed or insoluble solids are mixed with water it
forms negative mixtures. For preparing such types of
mixtures a high degree of mixing material is required.
3) Neutral Mixtures: These mixtures are static in nature.
The substances do not have the tendency to mix with
each other immediately, but once mixed they do not
separate after mixing.
TYPES OF MIXTURES

4. The mixing of powders is one of the common pharmaceutical
operations and is used in the preparation of many type of
formulation, such as, tablets, capsules and compound powders.
MIXING OF POWDER
Mixing mechanism: The solid mixing takes place by a
combination of one or more mechanisms given below :-
 Convective mixing: There is bulk movement of groups of
particles from one part of powder bed to another. It occurs by an
inversion of powder bed by means of blades or paddles.
 Shear mixing: When shear forces occur it reduces the scale of
segregation by thinning of dissimilar layers of solid material.
 Diffusion mixing: It occurs when random motion of particles
within a powder bed causes them to change position relative to
one another. It is produced by any form of agitation of powder.

5. FACTORS AFFECTING MIXING
 Particle size: Should be approximate same particle size
 Particle shape: Must be spherical for uniform mixing
 Particle attraction: Some particles exert attractive forces due
to electrostatic charges on them. This can lead to separation.
 Material density: For uniformmixing of powders, proper
attention should be given to their density.
 Proportion of materials: The best results can be achieved if
two powders are mixed in equal proportions by weight or by
volume. In case there is a large difference in the proportion of
two powders to be mixed the mixing of powders is always
done in the ascending order of their weights.

6. Equipment Used for Mixing of Powders
In the laboratory, the mixing is done by using
pestle and mortar or with the help of a drug
spatula. The method is commonly known as
'trituration'.
On large scale, the following equipment are
used for mixing of powders:
1. Tumbler mixer
2. Double cone mixer
3. Agitated powder mixer
4. Air mixer

7. Tumbler Mixer :- It consists of metallic vessel in
which powders are mixed by slow rotation, either
manually or with the help of an electric motor. Due
to rotation the ingredients come over one another.
For mixing at large scale, mixing is done in a vessel
of a suitable design along with baffles which gives a
thorough mixing. The tumbler mixers are generally
made up of stainless steel with various design like
cubical, v, y, cylindrical shapes etc.
The rotation of vessel should be slow so that the
powder does not remain stationary against the side of
vessel held by centrifugal force but lifted by baffles
and fall over continuously.

8. Double Cone Mixer :- The mixing of powder in this due to
tumbling and shearing action with blade. This is made of
stainless steel and is available in different capacity ranging
from 5 to 200 kg or even more. The efficiency of the
blender depends mainly on the speed of rotation. The rate of
rotation should be optimum which depends on the size and
shape of tumbler as well as nature of material to be mixed.
The common range is 30-100 r.p.m.
The material to be blended is loaded approximately 50-60%
of the total capacity of the blender. As the blender rotates
the material undergoes tumbling motion and mixes the
material thoroughly. Agitator blade can also be fixed in
order to produce shearing action.
This is used for mixing powders of different densities and is
used mainly for small quantity of powers.

9. Agitated Powder Mixer: It consists of a stationary vessel or
a trough in which an arm rotates and transmits shearing
action to the particles. The end to end movement is required
for general mixing which can be achieved by fitting helical
blades to the agitator. The mixer is commonly used for
mixing free flowing powdered materials having uniform
particle size and density.
Air Mixer: The air movement can be used for mixing of
powders. The powder to be mixed are taken in a vertical
cylindrical vessel and air is admitted at its base at an angle
after short interval blasts. This gives a spiral movement to
the powder. The air should be admitted at short intervals and
not continuously. A typical method is to use eight air blasts
of two seconds duration with one second interval. Thus 24
seconds are required for proper mixing.

10. MIXING OF LIQUIDS
Mixing of liquid is done to prepare true solution or
emulsions. Mixing is required to dissolve one miscible
liquid into another miscible liquid to form true solution. For
making emulsion, the mixing of two immiscible liquids are
done by using shear force.
Equipments for liquid mixing In laboratory the emulsion
is prepared by using motor and pestle and afterward it is
passed through homogenizer to get fine emulsion. On large
scale following equipment are used :-
1. Propeller mixer
2. Turbine mixer
3. Paddle mixer

11. Propeller Mixer : It consists of a vessel and a propeller. The propeller
operates at high speed which is up to 8000 r.p.m. which gives a satisfactory
flow pattern to the liquids. During mixing of liquids, air get entrapped in
liquids or there is formation of vortex. This can be avoided by making
following changes in the position of propeller shaft:
a) Offset from the centre
b) Mounted the angle
c) Enter the side of the vessel
d) Using push pull propeller
e) By use of baffles
Turbine Mixer : It consists of a vessel and a circular disc impeller. A number
of short, straight or curved blades are attached to it. The turbine impeller is
usually rotated at somewhat lower speed than the propeller. This is used for
mixing of more viscous liquids.
Paddle Mixer : In this, the flat blades are attached to a vertical shaft which
rotates at low speed of 100 r.p.m. For mixing the low viscosity liquids simple
flat paddles are used. But for mixing high viscosity liquids, the big paddles
often shaped to fit closely to the surface of vessel, are used.

12. MIXING OF SEMI SOLIDS
This is done for preparing ointments, creams, pill
masses and wet mass for making granules etc.
Equipments for mixing of semisolids:-
1. Triple Roller Mill
2. Agitator Mixer
3. Planetary Mixer

13. Triple Roller Mill:
Construction : The mill consists of three roller which are made of a hard abrasion-
resistant material. These roller are arranged in such a way that they come very close
to each other and rotated at different rates of speed. The material coming between the
roller is crushed depending on the gap between them and the difference in rates of
movement of the two surfaces.
Working : The material after passing through hopper, comes between roller 1 and 2
and is reduced in size in size the process. The gap between roller 1 and 3 is usually
less than that between 1 and 2, further crushes and smooths the mixture which
adheres to roller 2. A scraper is arranged in such a way, that it can be remove the
mixed material from the roller no 3 and does not allow the material which has not
passed between both sets of the roller to reach the scarper.
Uses : for the purpose of mixing of solid powder in ointment base.

14. Agitator Mixer: This is used for mixing liquids and powders. Sigma arm
mixer is commonly used agitator mixer for the purpose of semisolid mixing. The
mixer has two blades, the shape of which resembles the greek latter “Sigma”. The
two blades move at different speeds and towards each other. The blades operate in a
mixing vessel which has double trough shape, each blade fitted into a trough. The
two blades rotates at different speeds, one usually about twice the speed of other
which cause the lateral pulling of the material and is divided into two troughs. The
difference in speed and shape of blades causes end-to-end movement. Air
entrapment can be avoided by enclosing the sigma arm mixer and operating it under
pressure.
Uses : Used for mixing of dough ingredients in baking industry.
Used in wet granulation process in tablet manufacturing.
Used for mixing powdered drug with an ointment base.

15. Planetary Mixer:
Principle : In this, the blade tears the mass apart and shear is applied between a
moving blade and a stationary wall. The mixing arm moves around its own axis and
also around central axis in order to reach every spot of the vessel. The plates in the
blades are sloped, so that the powder makes an upward movement to produce
tumbling motion.
Construction : It consists of a stationary vessel which is made up of stainless steel.
The vessel can be removed either by lowering it beneath the blade or raising the
blade above the vessel. The mixing blade is mounted from the top of the vessel. The
mixing shaft is driven by planetary gear connected to an electric motor.
Working : The blade is moved slowly at the initial stage for premixing of the
material and
finally at increased speed for active mixing. In this way high shear can be applied
for
thorough mixing. The blade and the stationary vessel provide a kneading action and
shear. This is due to narrow clearance between the blade and the wall of the vessel.
Uses :
 Used in wet granulation
 Used for mixing of powdered drug with an ointment base.

16. HOMOGENIZATION
Homogenization is the process of preparing fine emulsion
from a coarse emulsion by converting large globules to
small globules. Homogenization is done in an apparatus
called homogenizer.
Principle : Based on the principle that the large globules in
a coarse emulsion are broken into smaller globules by
passing them under pressure through a narrow orifice.
The commonly used homogenizer are:
1. Hand homogenizer
2. Silverson mixer homogenizer
3. Colloidal mill

17. Hand homogenizer: It is hand operated and the coarse emulsion is
passed through fine orifice. The emulsion is placed in the hopper of the
homogenizer. The up and down movement of the handle cause coarse
emulsion to draw in through inlet valve. In this way the emulsion is
forced to pass through the fine orifice(aperture). The oil globules are
broken into fine globules of uniform size.
Silver mixer homogenizer:
Construction: It consists of an emulsifier head which is covered with
fine meshed stainless steel sieve. The emulsifier head consists of a
number of blades which rotate at a very high speed, in order to produce a
powerful shearing action. The blades are rotated by using an electric
motor fitted at top.
Working: the emulsifier head is placed in the vessel containing
immiscible liquids, in such a way that it should get dipped into it. When
the motor is started, the liquids are sucked through the fine holes and the
oil is reduced into fine globules due to rotation of the blades.
So a fine emulsion is produced which is then expelled out. The intake
and emulsion of the mixture set up a pattern of circulation.

18. Colloidal Mill:
Principle: The size reduction is affected due to shearing, when the
material is passed between the narrow gap of milling surface of rotor
and stator.
Construction: Colloidal mill consists of a rotor and a starter. The rotor
rotates at a speed of 3000 to 20000 r.p.m. The starter have conical
milling surfaces between which there is an adjustable clearance
between 0.002 to 0.03 inches.
Working: The material e.g. emulsion and suspension is placed into the
hopper of the mill. It is then passed through the narrow gap between
the rotor and starter and thus reduced to fine particle size.
Uses:
1. Colloidal mills are capable of producing particles in micron size.
2. These are commonly used to prepare pharmaceutical suspensions
emulsions having particle size less than one micron.