This document discusses various methods for preparing novel emulsion systems, including multiple emulsions, microemulsions, and nanoemulsions. It describes multiple emulsion as emulsions of emulsions containing an internal phase dispersed in an intermediate phase that is then dispersed in an external continuous phase. Various preparation techniques are outlined, including two-step emulsification, phase inversion, and membrane emulsification methods. Microemulsions are described as thermodynamically stable, transparent or translucent systems formed using surfactants and cosurfactants. Methods for microemulsion preparation include phase titration and spontaneous emulsification. Nanoemulsions are defined as oil-in-water emulsions with droplets between 50-100 nm prepared using
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Methods of preparation of novel emulsion
1. Methods of Preparation
of Novel Emulsion
1
Presented By
Manali Parab
M.Pharmacy Ist year (Sem Ist)
Pharmaceutics Department
2. Emulsion
Emulsion can be defined as heterogeneous
system where one immiscible liquid is
dispersed in another in the form of droplets
and stabilized by third component called
emulsifying agent
These have been described as heterogeneous
systems of one immiscible liquid dispersed in
another in the form of droplets, which usually
have diameters greater than 1 μm .
Types of emulsion
Oil in water (o/w)
Water in oil (w/o)
2
4. MULTIPLE EMULSION
Multiple emulsions are more complex systems as the drops of
the dispersed phase themselves contain even smaller dispersed
droplets which normally consist of a liquid which is miscible,
and in most cases, is identical with the continuous phase.
They are therefore, emulsions of emulsions. For each type of
multiple emulsion, the internal and external phases are alike
and an intermediate phase separates the two like phases.
The intermediate phase is immiscible with the two like phases.
An emulsifier is present to stabilize the emulsion and a variety
of ionic and non-ionic surfactants are available for this
purpose.
Lipophilic (oil-soluble, low HLB) surfactants are used to
stabilize W/O emulsions, whereas hydrophilic (water-soluble,
high HLB) surfactants are used to stabilize oil/water systems.
4
5. The oil layer acts as a membrane separating these two aqueous
phases.
Polar molecules dissolved in either the internal aqueous phase
or the external continuous aqueous phase can pass through the
oil layer by diffusion because of the concentration gradient.
In the case of water this is driven by osmotic pressure.
Molecules are often transported via micelles of hydrophobic
surfactant present in the oil phase. Water diffusion causes
swelling, bursting, or shrinkage of the internal aqueous
droplets, affecting the stability of the multiple droplets as well
as the release profiles of the active ingredients loaded in the
inner dispersed aqueous phase
For eg. Valsartan multiple emulsion
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7. Method of preparation
Two step emulsification
Phase inversion technique
Membrane emulsification
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8. Two step emulsification
Complex system
Liquid membrane
system
Thermodynami
cally stable
Low HLB added to
Oily phase
Low HLB:
Hydrophobic
High HLB:
hydrophobic
Require two
emulsifier
Multiple emulsion
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9. Multiple emulsion w/o/w contains two types of emulsifier
Low HLB surfactants ( hydrophobic in nature)
High HLB surfactants ( hydrophilic in nature)
Low HLB surfactants are used in dispersed phase
High HLB surfactants are used in continuous phase
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12. Phase inversion technique/
one step emulsification
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Oil +lipophilic surfactant
aqueous solution +
hydrophillic emulsifier
migration of the emulsifier between phases
concentration of dispersed globules in dispersion
medium is quite high i.e., globules are packed
very closely in suspending fluid.
w/o/w emulsion
14. Membrane emulsification
technique
In this method, a w/o emulsion (a
dispersed phase) is extruded into an
external aqueous phase (continuous phase)
with a constant pressure though a porous
glass membrane.
The particle size can be controlled by
controlling size of porous glass membrane.
Porous glass used is Shirasu porous glass
given by SPG technology Miyazaki, Japan
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15. The relation between membrane pore size and particle
size of emulsion exhibits good correlation as
described by the
formula:
Y= 5.03X + 0.19
Where,
X= the pore size
Y= the mean particle size
A micro porous glass membrane with narrow pore size
range was used successfully for preparing stable
simple (o/w) and water-oil-water (w/o/w) type
emulsion
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16. Cross-Flow Membrane
Emulsification
To prepare monodisperse emulsion using a particular
glass
membrane called Shirasu Porous Glass (SPG)
membrane (SPG Technology, Miyazaki, Japan)
In cross-flow membrane emulsification, the
dispersed phase is pressed through a microporous
membrane (micropore diameter is dp) while the
continuous phase flows along the membrane
surface. Droplets grow at micropores and detach
at a certain size (dd), which is determined by the
balance between the forces acting on the droplet.
Emulsifiers in the continuous phase stabilize the
newly formed inter-face, to prevent droplet
coalescence immediately after formation.
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17. DISADVANTAGES
Direct membrane emulsification (DME). There are some
potential disadvantages
with this technique
(i) the relatively low maximum dispersed phase flux (typically
0.01–0.1m3
/(m2
h)) that leads to low productivity;
(ii) it is difficult to prepare uniform emulsion droplets when the
dispersed phase has high viscosity
.
17
18. (iii) Uniform emulsion can only be
prepared using a microporous membrane
with very uniform pores. Because of these
restricted conditions, there have been some
limitations in choosing the dispersed
phase, the continuous phase, and the
membrane to obtain the desired
emulsification products
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25. Formulation
Microemulsion formulation is specific to
the nature of oil/surfactant pair, surfactant
concentration and the oil/surfactant ratio,
the concentration and nature of co-
surfactant and surfactant/co-surfactant ratio
and the temperature.
Hence main components of microemulsion
system are as follows
Oil phase
Primary surfactant
Secondary surfactant (co-surfactnt)
Co-solvent
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27. Methods of formulation of
microemulsion
Phase titration method (water titration method)
Microemulsion are prepared by spontaneous
emulsification method (phase titration method) and
can be depicted using phase diagrams.
Microemulsion formed with several association
structures (emulsion, micelles, various gels and oily
dispersions) depending on chemical composition and
concentration of various substances
As quaternary phase diagram is difficult to interpret,
pseudo ternary diagrams are constructed to find out
different zones, in each corner of the diagram
represents 100% of each component
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28. Ternary phase diagrams
Number of intermediate structural phases, including
bicontinuous, lamellar, hexagonal and multiple
phases, when a mixture of surfactant and oil at certain
ratios is mixed gradually with water.
Bicontinuous structure may exist in systems where
the amount of water and oil are similar and both oil
and water exist as a continuous phase
Multiple phases may exist where there is insufficient
surfactant to form a single microemulsion phase,
particularly for compositions close to the oil-water
binary axis
The transitions between the various phases mapped
out in the phase diagram can be driven by changing
the temperature or addition of a component
28
29. Preparation of samples for
analysis and construction of phase
diagrams
1. One is titration of a mixture of two components
with the third component, for example, using water
to titrate the mixture of surfactant and oil.
2. The other is preparation of a large number of
samples with different compositions (i.e. different
ratios of three components)
In order to speed up the process, heat and
sonication are often employed in the
experimentation
29
32. Emulsion titration/dilution
method This method involves a two step process in which a premade
nonionic surfactant stabilized (e.g. Tween 80) o/w
conventional emulsion is diluted into an aqueous surfactant
micellar solution (e.g. 1% Tween 80)
This method can thus be called ‘emulsion titration or dilution
method’, however, this method involves both high energy and
low energy methods
Formation of microemulsions by the emulsion dilution method
was shown to be highly dependent on the concentration of oil
in the final mixture.
This means that the level of oil concentration required to be
diluted into the surfactant solution to enable to form
microemulsions (e.g., oil droplet size smaller than 50 or 100
microm) is limited and determined by the amount of titrated
conventional emulsion into a surfactant solution
This method has also been called “oil exchange”, “swelling of
o/w emulsion”, “oil solubilisation” or “molecular transport”
32
33. It was shown that the size of oil droplets smaller than
100 nm could be formed by this approach only when
a oil concentration added was lower than 1.5 wt% oil
in the final mixture
When the volume of emulsion added has a relatively
low concentration of oil droplets, all of the oil
molecules in the emulsion move out of the droplets
and are incorporated into the surfactant micelles.
several possible mechanisms
(1) oil molecules are directly solubilized in water, and
then they are accommodated by micelles in the
aqueous phase;
(2) oil molecules are incorporated into micelles due to
the collision of micelles with the surface of emulsion
droplets;
33
34. DISADVANTAGES
Certain types of emulsifiers can be used which are
limited to mostly nonionic small molecule
surfactants
Certain types of low viscosity and non triglyceride
oils, and the level of oil concentration should be
low
34
39. Nanoemulsion
Nanoemulsion can be defined as oil in water
emulsion with mean droplets diameters ranging from
50 to 100nm.
It is also called as sub micron emulsion or mini
emulsion
These are group of dispersed particles used for
pharmaceutical and biomedical aids and vehicles that
show great promise for cosmetics, diagnosis, drug
therapies and bio technologies.
Due to their small droplet size Nanoemulsions
possesses stability against sedimentation or creaming
with Ostwald forming main mechanism
Nanoemulsions breakdown.
39
40. Methods of formulation of
nanoemulsion
High pressure homogenization
In high pressure homogenizer, the dispersion of
two liquids (oily phase and aqueous phase) is
achieved by forcing their mixture through small
inlet orifice at very high pressure (500 to
20000psi), which sublet the product to intense
turbulence and hydraulic shear resulting in
extremely fine particles of emulsion.
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41. Aqueous phase+ oleaginous phase (heated and pH adjustment)
heated and filtration
41
Add emulsifying agent
Rapid cooling
High pressure homogenizer (500 to 20000psi)
Formation of droplets of very small size
43. Microfluidization
Microfluidic technologies are indicated to manipulate
small quantities of liquids or fluids usually through
channels with at least one dimension smaller than 1
mm, for emulsion formation, mixing and dispersion.
Microfluidizer high shear fluid processors are unique
in their ability to achieve uniform particle size
reduction, bottom-up crystallization and efficient cell
disruption.
Product enters the system via the inlet reservoir and is
powered by a high-pressure pump into the interaction
chamber at speeds up to 400 m/s.
43
44. An interaction chamber where two channels of fluid
flow at high velocity and collide with each other
When the fluids from the two channels collide, it
generates intense, disruptive forces that result in very
small emulsion droplets.
It is then effectively cooled, if required, and collected
in the output reservoir.
The exclusive fixed-geometry interaction chambers
combines with a constant pressure pumping system to
produce unparalleled results
44
47. Ultrasound emulsification
In this method, a probe emits ultrasonic waves (20kHz)
to disintegrate microemulsion by means of cavitation
forces.
In the dispersing zone, imploding cavitation bubbles
cause intensive shock waves in the surrounding liquid
and result in the formation of liquid jets of high liquid
velocity.
n order to stabilize the newly formed droplets of the
disperse phase against coalescence, emulsifiers (surface
active substances, surfactants) and stabilizers are added
to the emulsion.
47
48. As coalescence of the droplets after disruption
influences the final droplet size distribution,
efficiently stabilizing emulsifiers are used to maintain
the final droplet size distribution at a level that is
equal to the distribution immediately after the droplet
disruption in the ultrasonic dispersing zone.
By varying ultrasound energy input and time, the
nanoemulsion of desired properties can be obtained.
Undesirable for thermolabile drugs and
macromolecues (retinoids, proteins, enzymes and
nucleic acids)
48
20 - 500 Å, and so is much smaller than the wavelength of light (4000 Å ≤ l light ≤ 7000 Å). Hence, microemulsions are generally weak scatterers of light, and this explains their transparency.