Disperse Systems

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Introduction
Disperse systems fall into two categories
Emulsions
Suspensions
In addition, pharmaceutical products contain
API, which may be solid or liquid, uniformly
dispersed into the emulsion or dispersion base
Hence, many types and variations of mixing,
dispersion, emulsification and size reduction
equipments can be used to prepare disperse
systems
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Factors influence selection
process
Suspension
Viscosity
Density
Particle shape, size and size distribution
Emulsion
Surface tension
Chemical activity of liquid phases
Surfactants
Stabilizers

Parameters
Relationship of Mixing equipment to viscosity
A large no. of dispersed products exhibit
Plasticity
Pseudo plasticity
Thixotropy
Macroscale versus Microscale mixing
Macroscale mixing refers to adequate flow in all
areas of mixing vessel (also called as blending)
In microscale mixing individual components are
mixed
Mixer power equation
P = C.[ ND
2
/]
-a
.[ N
2
D

/g]
-b

N
3
D
5
Where
P= power consumed
D= impeller diameter
N= speed of rotation
g= acceleration due to gravity
= liquid density
= viscosity
a & b = exponents determined experimentally
C= proportionality constant
[ ND
2
/] = Reynolds number, [ N
2
D

/g] = Frounde number
When flow is laminar , a is close to 1 & b is close to zero
When flow is turbulent both the exponents are close to zero

Methods
Blending of miscible liquids
Suspension of solids
Dispersion of solids (size reduction)/
emulsification
Emulsification of immiscible liquid systems
Preparation of liposomes
Scale up
Vacuum processing
Scale up
Scale up ratio = large scale production rate
small scale production rate

Scale up ratio 10 to 100 for laboratory to pilot
and 10 to 200 for pilot plant to commercial
production

Scale up parameters
Power P
P/V ratio= power consumed/ vol. of Vessel
Tip speed of impeller = DN
Pumping rate per unit volume, Q/V
Pumping rate Q ND
3

Geometric, kinetic and dynamic similarity



Scale up
For dispersions, the controlling factor is often
tip speed, which determines the maximum
shear rates.
Never use laboratory scale or pilot scale
equipment that can not be built or operated in
larger sizes
Optimization of scale up around only one
parameter is not usually feasible. Some
compromises are normally necessary
Vacuum processing
Presence of dispersed air is almost a detrimental
factor to emulsion stability
All mixing steps should be conducted to incorporate
least amount of air
One way of combating the aeration problems is to
perform the entire process in a vacuum
Vacuum processing also allows the option of
drawing powders into batch from the bottom outlet.
This promotes immediate dispersion
Foam may form even during processing under
vacuum.
Steps to prevent foam
formation
Gentle mixing is best for initial deaeration
step
Increase the absolute pressure (decreasing
the vacuum) outside of the foam bubble to
crush bubble
By increasing and then decrease in the
vacuum, the batch can be deaerated
Devices are available for deaeration on
continuous basis.
Mixing equipment
A. Mixers
B. High speed dispersers
C. Rotor stator mixers
D. Combination mixers
E. In- line mixers
F. Non- mechanical disperse processing
G. Fine suspension and size reduction
equipment
Mixing equipment
A. Mixers
Propeller mixers
Turbine mixers
Anchor mixers
Scraped surface agitators
Counter rotation

B. High speed Dispersers
Design: Also called as saw blade disperser
This machine consists of a variable speed shaft
connected to an impeller with a serrated edge
The tip speed is set around 4000 ft/min
The diameter of impeller should be 1/3 of diameter of
vessel
The impeller should be located one impeller diameter
off the bottom of vessel
Application: This is used to disperse pigments into liquids
Limitation: The high speed disperse design is ineffective if
the viscosity is low
Suitable for suspensions not emulsions
Air incorporation is another problem
C. Rotor/ stator mixer
Radial flow with stator
Rotating stator:
In this both impeller and the stator both rotate on
drive shaft and hence produce combined shear
Hence no supporting rod necessary and no
steady bearing is required
Axial flow rotor/ stator mixer

D. Combination Mixers
Anchor plus Rotor/ stator
Anchor plus high speed disperser
In line Mixers
Rotor/stator mixer disperser emulsifiers
Colloid mills
Piston homogenizers
Ultrasonic vibrating homogenizer
Micro fluidizer technology
Low pressure cyclone emulsifiers
Static mixers: pipe line mixers contain series
of baffles in a cylindrical pipe
Microfluidizer Technologies
This device uses a high pressure positive displacement
pump operating at pressure 500-20000 psig through
interaction chamber.
The interaction chamber consists of microchannels as
narrow as 50 microns and cause the flow of product to
occur as very thin sheets
Microchannels are Y- shaped divides flow into two
micro streams
At the impingement area the collision of two high speed
flow streams in a very tight spot creates various droplet
size reductions and mixing
This technology is used to prepare unilamellar
liposomes and micro emulsions
F. Non mechanical disperse
processing
Critical fluids liposome process
Super critical or near critical fluids are gases CO2 and propane
under ambient conditions
When compressed at conditions above their critical temperature and
pressure, these substances become fluids with liquid like density
and gas like properties of low viscosity and high diffusivity.
The gaseous characteristics increase mass transfer rate, thereby
decrease processing time
A circulating pump operating in a high pressure loop ensures good
mixing between the supercritical fluids and the liposomal raw
materials
After specified residence time, the resulting mixture is trough the dip
tube with its nozzle in a decompression chamber that contains
aqueous solution or fine dispersion of drug for liposomal
encapsulation.
Fine suspension and size
reduction equipment
Three roll mills
Ball mills or jar mills
Continuous stirred media mills
Three roll mills
Capable of dispersing small tightly bound
agglomerates and hard discrete particles
Premixed suspension allowed to travel
between rotating rolls that are located about
10- 50 microns apart.
The particles not only subject to very high
shear mechanical crushing and smearing
Three rolls are named as feed roll, center roll
and apron roll
Three roll mills
The shear rates in a three roll mill are a
function of
The roll radius, R inches
The difference in rpm of the rolls in contact, rpm
Clearance between the rolls known as nip
clearance, z (mils)
Shear rate, = 105R /z
Ball mill
For true size reduction of fine particles or for
deagglomeration of very tightly bound
agglomerates
Small version of ball mill is known as jar mill
Disadvantage is time consuming process
For difficult to grind materials, ball mill is still
the machine of choice
Agitated bead mills
Just like ball mill ,the bead mill uses a charge
of inert small balls around 2-8mm in diameter
If the beads are ceramic media mill
If the beads are steel balls- shot mill
Large grains of sand(3mm)- sand mill
The cylinder is either horizontal or vertical
Not often used in ph. industry, except when
particle size requirements fall below 10
microns
References
Disperse systems,vol-1 to 3
Remingtons pharmaceutical
sciences
Ansels pharmaceutical dosage
forms
Dispencing pharmacy by cooper
and gunn
THAN-Q-U