Mixing

Definition:

A process of intermingling of two different materials

to attain a desirable uniformity in the final product.
Mixing is probably the most widely performed
operation in pharmaceutical manufacturing.

Mixing = blending
Demixing = unblending = segregation

Mixing is done for

1.Powder mixing: a blend of solid particles.
2.Liquid mixing: a mixture of two liquids,
or to dissolve of suspend solid in a liquid.
3.Semisolid mixing: a dispersion of
particles in a semisolid as in the
preparation of ointments or pastes.

Objectives of mixing
Simple Physical Mixture
To secure uniformity of dosage forms to ensure
correct dose. (ex, dilution of a potent drug).
Dispersion
This includes the dispersion of two immiscible
liquids to form an emulsion or the dispersion of a
solid in a liquid to give a suspension.
Promotion of Reaction
Mixing will usually encourage and control a
chemical reaction, so ensuring uniform products.

Types of Mixtures:
Type

examples

Mixing

Segregation

Positive
mixtures

Miscible liquids

No need for
energy

Irreversible

Negative
mixtures

Suspensions

Needs energy

Reversible

Neutral
mixing

Creams and
ointments

Need energy

Irreversible

Degree of mixing:
Perfect (ideal) mixing indicates that each particle of one

component lies in contact with a particles of other ingredients.

Scale of scrutiny
It the mixture amount or volume containing the

drug dose.
This amount (scale of scrutiny) must be
examined/analyzed to ensure that it contains
the correct dose.
e.g. if the unit weight of a tablet is 200 mg then
a 200 mg sample from the mix needs to be
analyzed to see if mixing is adequate.
The scale of scrutiny therefore = 200 mg

Mechanisms of powder mixing

1. Diffusive mixing:
.By tilting the bulk of the material slipping of upper layers
will lead to mixing of the powders.
.E.g. tilting of paper carrying two types of powder.

2- Shear mixing:
The use of an agitator arm will create shear forces in the
powders.
E.g. mortar and pestle.

3- Convective mixing:
It is the transfer of a group of adjacent particles from one
location to another.
Eg. Insertion a spatula into a heap of powder withdrawing

a small amount of powder on its blade deposition of it

elsewhere.

Factors affecting mixing of solids:

1.Particle size & density difference: :
The large particles (Heavy particles) will
roll and flow over one another and settle to
the bottom of the mixer.
2. The small particles (light particle) tend to
move to the surface.
1.

.This could be minimized by: keeping

particle size uniform.

2-Electrostatic charge:
Friction of particles formation of similar

charges on the particles segregation

This could be minimized by:
1. Stop the mixing when a satisfactory blend is
obtained.
2. Addition of SAA (if permissible) to neutralize the
surface charges.

Conditions for good mixing:

1- Optimum space: to allow expansion and
movement of powder, over filling prevents mixing.
2- Optimum mixing time: otherwise, electrostatic
charges, due to friction, may lead to repulsion and
segregation.
3- Optimum handling of the mixture: the
mixture must be handled carefully to avoid any
vibration to minimize segregation the formed
mixture must be used in the next process
directly after mixing.
4- Use equipment where several operations can be
carried out without transferring the mix e.g. a
fluidized-bed drier or high speed mixer (Diosna) for

Types of mixers of dry powders:

1.Tumbling mixers: by tilting the material.

e.g. barrel mixer, cube mixer, double cone

and V-mixer. (Diffusive)
2.Agitator mixers: which shear is applied

by means of agitating arms (e.g. Ribbon

blender, Nautamixer and high shear mixer
(Diosna).

Tumbling mixers
Diffusive mixing predominates used

mainly for free flowing powder and

granular material
They include:
Barrel mixer.
Cubic mixer.
Double cone mixer.
V-shaped mixer.

Tumbling mixers
Barrel mixer
A barrel or drum
characte
rotating around axis rs
Inlet & outlet are the
same
1. Simple design
Adv.
2. Ease to clean

Shear force is low

Disadv.

Cube mixer
It has flat surface.
Inlet & outlet are
the same
Easy to construct
-Has corners so it is
difficult to be cleaned

character
s
Adv.
Disadv.

How to overcome cleaning problems in

cube mixer??

make semicircular corners instead of sharp

corners

Double cone mixer

2 cones are joined to characters
relatively short
cylindrical section,
The rotation axis is
centrally located on
the cylindrical portion
Most widely used in
factories

V-shaped mixer
2 inclined cylindrical sections and

Charact.

joined to form V shape

Internal baffles may be provided to
mixing efficiency
It has separate inlet and outlet
Ease of cleaning because all interior
surface can be reached through the
charge and discharge openings

Adv.

Factors to be considered in
operating Tumbling mixers
1-Optimum speed should be used :
*Too low speed very mild powder diffusion
*too high speed centrifugation hence segregation.

2. Charging capacity: The mixer should be

charged with no more than 50% - 60% of total
capacity to provide sufficient space for powder
movement.
3. Method of charging: E.g. by adding the
components together side by side

Advantages of tumbling mixers:

they produce mild forces gentle
mixing with no grinding so its used
for:
Friable fluffy material, e.g. Granules.

N.B. Baffles can be added to all tumbling

mixers to increase mixing efficiency.

Agitator mixers for powders

A. Horizontal ribbon
blender
A ribbon mixer is a stationary trough with semicircular bottom fitted
with a longitudinal shaft
It has 2 spiral ribbons; an outer ribbon moves the material in one
direction and an inner ribbon moves it in the opposite direction.
The outer ribbon maintains a fairly close clearance with the shell
bottom no stationary material remains adhering to the shell

 The mixing occur due to :

Mainly Convective effect of ribbons
Shearing action
Little Diffusive mixing (sliding on the semi circular bottom)

It is used for:
Mixing powder which do not flow freely (poor flowability) and
tend to aggregate

*disadvantages:
1. Produce some size reduction for the material

2.It requires high power.

B- Nauta mixer: (ideal mixer)

It consists of conical vessel with rotating arm

carrying helical conveyer.

3 different mechanisms
acting EQUALLY for mixing:

It combines the

1.Diffusive (conical vessel).

2.Convective (helical conveyer).
3.Shear mixing (small distance).

Advantages:
1.No dead points.

ItCconsists
a vessel
containing
3 blades
High of
Shear
Mixer
(Diosna):
rotor.
Used for:
1.Mixing.
2.Granulation by adding a binder
(granulating fluid) wet mass (paste)
The chopper cut the wet mass into
granules.
3.Drying by vacuum

Advantages of multi process equipment

Low labor cost
Low operation cost
Decrease material loss
Decrease the possibility of mixture

segregation.

II. Mixers for semisolid

materials
1.Beaters
2. Kneaders
3. Mixer extruders
4. Mixing rollers

1-Beaters:
Hobart's mixer (planetary mixer):
The arm rotates on its own axis and circulates round the vessel.
The arm visits all parts of the vessel (planetary movement) in a

stationary pan.

 The arm passes with close clearance (<1mm) over the side and

bottom of the mixing vessel... WHY?

1. To eliminate dead spots.
2. Provide self-cleaning action by scraping any material adhering to the
walls or the bottom of the vessel.
Suitable for mixing powders moistened with a liquid as before

tablet wet granulation.

jacketed for cold or hot process.

2- Kneaders:
Double arm mixer:
It consists of:
o A mixing vessel, in which 2 heavy arms or blades rotate on

horizontal shafts.

 Blades may be
(a) Sigma:
(b) Double naben:
(c) Dispersion:

- The mixing tank can be cooled, heated or operate under vacuum.

- It is used for:
a. Preparing tooth paste and ointments.
b. Processing volatile or harmful substances as it is a closed system.

3- Mixer extruders:

The operation depends on cutting and folding the material

Roto - feed mixer:
- The material is fed into large conical chamber where a helical

agitator cuts and folds the material on itself as it flows towards

the discharge end.

- Used to mix materials that are difficult to mix.

- Perform 3 main processes: mixing, size reduction

or size enlargement (granulation)

Outlet of roto feed mixer may be:
A single opening used for mixing
A narrow sieve used for size reduction
A wide sieve used for size enlargement

(granulation)

4- Triple roll mill:

It has 3 rolls, fit closely to each other and

rotate at different speeds.

- The material is subjected to intense shear by

repeated passage between rolls.

- It is transferred from roll to roll, taken from

the slower to the faster roll.

- The gap between the rolls is adjusted for controlling the fineness of

dispersion.
- The rolls can be cooled by passing water through the inside of the rolls.
It is used for 2 process operations
1. Size reduction.
2. Mixing of ointments and pastes.

III. Mixing of Liquids

(Agitation)
As velocity of liquid increased during mixing, the mixing will be

more efficient.

Mixing of 2 miscible liquids +ve mixtures

Mixing of 2 immiscible liquids -ve mixtures

Paddles
20-120 rpm (low speed)

120-200 rpm (moderate speed)

Turbines

propellers
400-1750 rpm (high speed)

Types of Paddles
Single paddle
For gentle mixing of

Gate Agitator
For mixing viscous

miscible low viscosity

liquids or thin pastes.

liquids.

Multiple-Blade

Anchor Paddle

For mixing viscous liquids ...

Is a poor mixer.

By moving them between stationary

It is used during evaporation to

baffles (arise from the vessel) and

prevent solid deposition on the heat

rotating paddle

transfer surface.

Types of
Turbines

Straight - Blade

Curved - Blade

Turbine

Turbine

Shrouded Turbine

Blades are straight.

Blades are twisted to Curved blade rotates inside

*It is used for: thin

semicircular.

liquids

*It is used for:

Viscous liquids

stator ring (static).

*It is used for:
emulsification.

Types of Propellers
Standard

Saw Toothed

Weedless

Guarded stator
ring

For mixing of
thin liquids

For mixing of viscous liquids

Has rotor blades

and a stator ring
For
emulsification