MIXING

Mixing 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 ingredients are treated so that every
particle of any one ingredient lies as near as possible to the particle of the other ingredient.
Or
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.
OBJECTIVES OF MIXING
• The main objective of this mixing is to produce a bulk mixture which when divide into different
doses, every unit of divided doses must contain the correct proportion of each ingredient. It is critical
process because the quality of the final product and its attributes are derived by the quality of the
mixing.
• 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 semisolid 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.
APPLICATIONS OF MIXING
Mixing is an intermediate step in production of tablet or capsule. Mixing of powders in different
proportion prior to granulation or tableting.
Dry mixing of materials for direct compression into tablets.
Dry mixing of powder or composites powders in capsule and insufflations, respectively.
Blending of powders are also important in preparation of cosmetic products such as facial powder
or dental powder.
In case of potent drugs where dose is low, mixing is critical factor. Otherwise, it will affect content
uniformity of tablet.
Shear mixing, in this, shearing force is created within the mass of material by induced a stress using a
stirring arm (shaft) connected to circular disc on which blades mounted on it or a burst of air.
 TYPES OF MIXTURES (EXTRA)
Mixtures may be classified as follows:
1. Positive mixtures
2. Negative mixtures
3. Neutral mixtures
Positive Mixtures – These types of mixtures are formed when two or more than two gases or miscible
liquids are mixed together or soluble solid is dissolved in water by means of diffusion process.
These types of materials do not create any problem in mixing. Mixture formed is irreversible.
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. Mixture formed is reversible.
Neutral Mixtures – Many pharmaceutical products such as pastes, ointments and mixed powders are
the examples of neutral mixtures. They are static in their behaviour. The components of such products
do not have any tendency to mix spontaneously but once mixed, they do not separate out easily.
MECHANISM OF MIXING IN SOLIDS & LIQUIDS (EXTRA)
In all type of mixers, mixing is achieved by applying one or more of the following mechanisms:
In solids different mechanisms of mixing exist such as:
➢ 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/ blades and baffles 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 micro mixing.
Depending on the flow properties 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. Non-cohesive materials – These materials flow readily such as grain, dry sand, plastic chips etc.
➢ In liquids different mechanisms of mixing exist such as
• Bulk transport
• Turbulent Mixing
• Laminar mixing
• Molecular diffusion
 FACTORS INFLUENCING MIXING (EXTRA)
􀂙 Nature of the product –
Rough surface of one of the components does not induce proper mixing. The reason for this is that
the active substance may enter into the pores of the other ingredient.
A substance that can adsorb on the surface can decrease aggregation, for e.g., addition of colloidal silica
to a strongly aggregating zinc oxide can make it a fine dusting powder which can be easily mixed.
􀂙 Particle size –
Variation in particle size leads to separation as the small particles move downward through the
spaces between the bigger particles. As the particle size increases, flow properties also increase due
to the influence of gravitational force on the size. It is easier to mix two powders having approximately
the same particle size.
􀂙 Particle shape –
For uniform mixing, the particles should be spherical in shape. The irregular shapes can become inter-
locked and there are less chances of separation of particles once these are mixed together.
􀂙 Particle charge –
Some particles exert attractive forces due to electrostatic charges on them. This results to separation
or segregation. Some particles tending to aggregate also.
􀂙 Proportions of materials to be mixed –
The proportions of materials to be mixed play a very important role in powder mixing. It is easy to mix
the powders if they are available in equal quantities but it is difficult to mix small quantities of powders
with large quantities of other ingredients or diluents.
DOUBLE CONE BLENDER
Principles of Double Cone Blender:
Double cone blender works on the principle of tumbling and shear action i.e.; the mixing of powder
take place due to tumbling action (Due to rotation of vessel) and shear action with the blades. The
Double Cone Blenders design is most often used for the intimate dry blending of free-flowing solids.
The solids being blended in these units can vary in bulk density and in percentage of the total mixture.
Materials being blended are constantly being intermixed as the Double Cone rotates. Normal cycle
times are typically in the range of 10 minutes; however, they can be less depending on the difficulty of
blending. The slant double cone design eliminates dead spots which occasionally occur in conventional
double cone mixer. The conical shape at both end enables uniform mixing and easy discharge.
Construction of Double Cone Blender:
 The conical shape at both ends enables uniform mixing and easy discharge.
The cone is statically balanced which protects the gear box and motor from any excessive load.
Powder is loaded into the cone through a wide opening and discharged through a butterfly or a Slide
valve. Inside the vessel agitator blades are also present.
Double cone blender is made up of stainless steel and available in different capacities ranging from
5 Kg to 200 Kg or more. The speed of rotation of double cone blender is about 30 to 100 rpm.
Working of Double Cone Blender:
The solid to be mixed is taken in the conical shape vessel. Due to rotation the powder starts to mix.
When the vessel starts to rotate the powdered material moves along the side of the vessel and it reaches
to the top position then from the top position the powder falls at the bottom of the vessel and thus mixing
takes place.
As the vessel rotates the material undergoes tumbling motion and agitator blades provide shearing
action to the material and mixing takes place thoroughly.
Uses of Double Cone Blender:
Double cone blender is used to produce homogeneous solid-solid mixture.
It is used for effective mixing of powder and granules.
The double cone blender machine is of canonical shape at both ends that provide uniform mixing of
granules in bulk.
Merits of Double Cone Blender:
If fragile granules are to be blended, double cone blender is suitable because of minimum attrition.
They handle large capacities.
Easy to clean, load, and unload.
This equipment requires minimum maintenance.
Demerits of Double Cone Blender:
Double cone blender needs high head space for installation.
It is not suitable for fine particulate system or ingredients of large difference in particle size
distribution, because not enough shear is applied.
If powders are free flowing, serial dilution is required for the addition of low dose active ingredients.
TURBINE MIXER
Principle of Turbine Mixer:
A turbine mixer is a mechanical device that is used in mixing different type of liquids.
The turbine mixer works mainly on the principle of shearing action.
Construction of Turbine Mixer:

Turbine consists of number of blades attached to the circular disk.

The blades used in the mixture are of various types: flat blades, disk-type flat blades, inclined
blades, curved blades, arrow headed blades, and so on.
The diameter of turbine varies from 30 to 50 percentage of the diameter of vessel.
It usually rotates at lower speed and the speed of rotation is about 50 to 200 rpm.
As compared to propeller turbines rotates at lower speed.
Working of Turbine Mixer:
When turbine mixer operates at sufficiently at high rotational speeds, the radial tangential flow
becomes pronounced with the formation of vortex.
It is necessary to install baffles in the vessel for the mixing process for uniform mixing.
The radial flow of the impeller impinges on vessel walls, where it slits in to two streams.
Merits of Turbine Mixer:
Turbines give greater shearing force than propeller.
Therefore, turbines are suitable for emulsification.
Demerits of Turbine Mixer:
Turbines have less pumping rate.
Uses of Turbine Mixer:
A turbine mixer suitable for viscous fluids (7.0 pascal-second).
Turbines used for thin paste and emulsification.
Turbines can also be used to handle slurries with 60 percentage solids.
Mainly used for semisolid materials.
SILVERSON EMULSIFIER/ Mixer/ Homogeniser
Principle of Silverson Emulsifier:
The silverson homogenizer works on the principle that the large globules in a course emulsion are
broken into smaller globules by intensive shearing forces and turbulence by high-speed rotors.
Construction of Silverson Emulsifier:

It consists of emulsifier head.

The emulsifier head consist of a number of turbine blades.
The blades are surrounded by mesh which is enclosed by cover having perforations.
The blades are rotated by using electric motor fitted at the top.
There is also one shaft whose one end is connected to motor and other end is connected to head.
Working of Silverson Emulsifier:
The emulsifier head is dipped in to the vessel containing immiscible liquids.
When the motor is started, shaft rotates the head.
Therefore, turbines blades also rotate at very high speed.
 The liquids are sucked trough the fine holes.
The complex flow pattern can cause droplet break up under either laminar or turbulent conditions
Centrifugal force expels the content through mesh and then to cover and subjects them to
mechanical shear.
This is followed by intense hydraulic shear.
The oil is reduced in to globules quickly resulting in a homogenous uniform product.
Then the fine emulsion emerge trough opening of cover.
As a result, bigger globules rapidly break in to smaller globules.
Merits of Silverson Emulsifier:
Fast and efficient.
They are used to get a fine droplet or particle size (2-5 microns).
Process efficiency is good.
Low operating cost.
Demerits of Silverson Emulsifier:
Chance of chocking of pores of mesh.
Uses of Silverson Emulsifier:
Used in preparation of creams, ointments, pharmaceutical suspension and emulsion of fine particle
size.
Triple Roller Mill
Principle
Triple roller mill works on the principle of milling by compression and shear action.
Construction
 It consists of three rollers which are made up of hard abrasion metals, the rollers are arranged in such
a way that they can come very close to each other.
These rollers are rotating at different rate of speed. Speed of rollers generally understood by this
statement. (3rd ˃2nd˃1st).
Hopper is attached between 1st & 2nd roller, Whereas the scraper is attached at 3rd roller. The gap
between roller 2nd & 3rd is usually less than the gap between 1st & 2nd roller.
Working
The materials to be mixed are put into the hopper. From the hopper the material comes between the
roller number 1 & 2 and the size of material is reduced in this process.
After this the material comes in between roller number 2 and 3, in this step the material becomes
more mixed and becomes smoother.
After mixing the material is removed with the help of scrapper which is present at the roller number
3.
Application
Triple roller mill is used for the mixing of solid powder in the ointment base.
It is also used in the process of ointment, cream and paste making.
It is also used for mixing of pharmaceutical materials, herbal and chemicals.