Transcript O/W Emulsions

Pharmacy Practice
1
Emulsion
Dr. Muslim Suardi, MSi., Apt.
Faculty of Pharmacy University of Andalas
An emulsion is a thermodynamically unstable two-phase system consisting of at least two immiscible liquids, one of which is dispersed in the form o
Emulsion
“A thermodynamically unstable twophase system consisting of at least
two immiscible liquids, one of which is
dispersed in the form of small droplets
throughout the other, & an
emulsifying agent”
Phase of Emulsion
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
Internal phase
Discontinuous phase:
Dispersed liquid
External phase
Continuous phase:
Dispersion medium
Oil-in-Water Emulsion
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Dispersed phase: Oils, petroleum
hydrocarbons, waxes
Continuous phase: water or an
aqueous solution.
O/W emulsion: generally formed if the
aqueous phase constitutes > 45% of
the total weight, & a hydrophilic
emulsifier is used.
Water-in-Oil Emulsion


Water or aqueous solutions are
dispersed in an oleaginous medium.
Generally formed if the aqueous phase
constitutes <45% of the total weight
& an lipophilic emulsifier is used.
Usage of Emulsions

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Many routes of administration.
Oral administration can be used, but
patients generally object to the oily
feel of emulsions in the mouth.
Some times, emulsions are choosed to
mask the taste of a very bitter drug or
when the oral solubility or BA of a
drug is to be dramatically increased
Topical Emulsions

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Creams:
Have emollient properties.
Can be o/w or w/o & are generally
opaque, thick liquids or soft solids.
Emulsions are also the bases used in
lotions, as are suspensions.
Lotion
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Not an official term, but is most often
used to describe fluid liquids intended
for topical use.
Lotions have a lubricating effect.
Intended to be used in areas where
the skin rubs against itself such as
between the fingers, thighs, & under
the arms.
Usage of Emulsions


Also used a ointment bases & IV-ly
administered as part of parenteral
nutrition therapy.
Their formulation & uses in these roles
will be covered in the appropriate
chapters.
Consistency of Emulsions


Varies from easily pourable liquids to
semisolid creams.
Consistency will depend upon:
Internal phase volume to external
phase volume ratio in which phase
ingredients solidify what ingredients
are solidifying
Vanishing Creams


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Stearic acid creams are o/w emulsions
& have a semisolid consistency but are
only 15% internal phase volume.
Many emulsions have internal phases
that account for 40% - 50% of the
total volume of the formulation.
Any semisolid character with w/o
emulsions generally is attributable to a
semisolid external phase
W/O Emulsions

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Tend to be immiscible in water, not
water washable, will not absorb water,
are occlusive, & may be "greasy."
This is primarily because oil is the
external phase, & oil will repel any of
the actions of water.
Occlusiveness is because the oil will
not allow water to evaporate from the
surface of the skin.
O/W Emulsions


Miscible with water, are water
washable, will absorb water, are
nonocclusive, & are nongreasy.
Water is the external phase & will
readily associate with any of the
actions of water
Emulsions Instability


By nature, physically unstable
Tend to separate into 2 distinct phases
or layers over time.
Instability


Creaming:
Dispersed oil droplets merge & rise to
the top of an o/w emulsion or settle to
the bottom in w/o emulsions.
Emulsion can be easily redispersed by
shaking.
Instability
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
Coalescence
Breaking or cracking: complete &
irreversible separation & fusion of the
dispersed phase.
Phase inversion
Change from w/o to o/w (or vice
versa) may occur.
Emulsifying Agents
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Emulsions are stabilized by adding an
emulsifier.
Have a hydrophilic & a lipophilic part in their
chemical structure.
All emulsifying agents concentrate at & are
adsorbed onto the oil:water interface to provide
a protective barrier around the dispersed
droplets.
In addition to this protective barrier, emulsifiers
stabilize the emulsion by reducing the
interfacial tension of the system.
Emulsifying Agents


Enhancing stability by imparting a
charge on the droplet surface thus
reducing the physical contact between
the droplets & decreasing the potential
for coalescence.
Commonly used: tragacanth, Na lauryl
sulfate, Na dioctyl sulfosuccinate, &
polymers known as the Spans® &
Tweens®.
Emulsifyer Classification


Chemical structure: synthetic, natural,
finely dispersed solids, & auxiliary
agents.
Mechanism of action: monomolecular,
multimolecular, & solid particle films.
Emulsifier Requirement
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Regardless of their classification, all
emulsifiers must be chemically stable,
inert & chemically non-reactive with
other emulsion components, nontoxic
& nonirritant.
They should also be reasonably
odorless & not cost prohibitive
Synthetic Emulsifiers
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Cationic
Anionic
Nonionic
Synthetic Emulsifiers
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Cationic & anionic surfactants are
generally limited to use in topical, o/w
emulsions.
Cationic:
Benzalkonium chloride
Benzethonium chloride
Cationic Agents
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Quarternary ammonium salts
Incompatible with organic anions
Infrequently used as emulsifiers.
Soaps are subject to hydrolysis & may
be less desirable than the more stable
detergents.
Anionic
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Alkali soaps:
Na or K oleate
Amine soaps
TEA stearate; Detergents: Na lauryl
sulfate, Na dioctyl sulfosuccinate, Na
docusate).
Nonionic
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Sorbitan esters (Spans®)
Polyoxyethylene derivatives of sorbitan
esters (Tweens®)
Glyceryl esters
Natural Emulsifier

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A variety of emulsifiers are natural
products derived from plant/animal
tissue.
Most of the emulsifiers form hydrated
lyophilic colloids (called hydrocolloids)
that form multimolecular layers around
emulsion droplets.
Hydrocolloid Emulsifiers
Have little/no effect on interfacial
tension, but exert a protective colloid
effect, reducing the potential for
coalescence, by:
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

Providing a protective sheath around the droplets
Imparting a charge to the dispersed droplets (so
that they repel each other)
Swelling to increase the viscosity of the system (so
that droplets are less likely to merge)
Classification of
Hydrocolloid Emulsifiers
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Vegetable derivatives: acacia,
tragacanth, agar, pectin, carrageenan,
lecithin
Animal derivatives: gelatin, lanolin,
cholesterol
Semi-synthetic agents:
methylcellulose, CMC
Synthetic agents: Carbopols®
Naturally Plant
Hydrocolloids
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Advantages: inexpensive, easy to
handle, & nontoxic.
Disadvantages: require relatively large
quantities to be effective as
emulsifiers, subject to microbial
growth & thus their formulations
require a preservative.
Vegetable derivatives are generally
limited to use as o/w emulsifiers.
The Animal Derivatives
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General form w/o emulsions.
Lecithin & cholesterol form a
monomolecular layer around the
emulsion droplet instead of the
typically multimolecular layers.
Cholesterol is a major constituent of
wool alcohols & it gives lanolin the
capacity to absorb water & form a w/o
emulsion.
Lecithin
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A phospholipid derived from egg yolk
Produces o/w emulsions because of its
strong hydrophilic character.
Animal derivatives are more likely to
cause allergic reactions & are subject
to microbial growth & rancidity.
Advantage: in their ability to support
formation of w/o emulsions
Semi-synthetic Agents
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Stronger emulsifiers, nontoxic, & less
subject to microbial growth.
Synthetic hydrocolloids: strongest
emulsifiers, nontoxic, not support
microbial growth.
Cost may be prohibitive.
Generally limited to use as o/w
emulsifiers.
Natural Emulsifiers
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
Derived from plant or animal tissue.
Most of them form hydrated lyophilic
colloids (called hydrocolloids) that
form multimolecular layers around
emulsion droplets.
Hydrocolloid Emulsifiers
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Little/no effect on interfacial tension,
but exert a protective colloid effect,
reducing the potential for coalescence,
by:
Providing a protective sheath around the droplets
Imparting a charge to the dispersed droplets (so that they
repel each other)
Swelling to increase the viscosity of the system (so that
droplets are less likely to merge)
Hydrocolloid Emulsifiers
Classification
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Vegetable derivatives: acacia,
tragacanth, agar, pectin, carrageenan,
lecithin
Animal derivatives: gelatin, lanolin,
cholesterol
Semi-synthetic agents:
Methylcellulose, CMC
Synthetic agents, e.g., Carbopols®
Plant Hydrocolloids
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Advantages
Inexpensive, easy to handle, & nontoxic.

Disadvantages
Require relatively large quantities to be
effective as emulsifiers
Subject to microbial growth, require a
preservative.
Generally limited to use as o/w emulsifiers.
Animal Derivatives
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General form w/o emulsions.
Lecithin & cholesterol form a
monomolecular layer around the
emulsion droplet instead of the typically
multimolecular layers.
Cholesterol: a major constituent of wool
alcohols & it gives lanolin the capacity to
absorb water & form a w/o emulsion.
Lecithin
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
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A phospholipid derived from egg yolk
Produces o/w emulsions because of its
strong hydrophilic character.
Animal derivatives are more likely to
cause allergic reactions & are subject
to microbial growth & rancidity.
Advantage: ability to support
formation of w/o emulsions.
Semi-synthetic Agents
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Stronger emulsifiers, nontoxic, & less
subject to microbial growth.
Synthetic hydrocolloids are the
strongest emulsifiers, nontoxic, & not
support microbial growth.
Cost may be prohibitive.
These synthetic agents are generally
limited to use as o/w emulsifiers
Finely Dispersed Solid
Particle Emulsifiers
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Finely Divided Solid Particle
Emulsifiers
Form a particulate layer around
dispersed particles.
Most will swell in the dispersion
medium to increase viscosity & reduce
the interaction between dispersed
droplets.
Finely Dispersed Solid
Particle Emulsifiers
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
Most commonly they support the
formation of o/w emulsions, but some
may support w/o emulsions.
Include: bentonite, veegum, hectorite,
Mg(OH)2, Al(OH)3 & Mg trisilicate.
Auxilarry
Fatty acids: stearic acid,
Fatty alcohols: stearyl or cetyl alcohol
Fatty esters: glyceryl monostearate
Serve to stabilize emulsions through
their ability to thicken the emulsion.
Have only weak emulsifying
properties, always used in combination
with other emulsifiers.
HLB System
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Hydrophile-lipophile Balance System
A system was developed to assist in
making systemic decisions about the
amounts & types of surfactants needed
in stable products.
Has an arbitrary scale of 1 - 18.
HLB numbers are experimentally
determined for the different emulsifiers
HLB System
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If an emulsifier has a low HLB number,
there is a low number of hydrophilic
groups on the molecule and it will
have more of a lipophilic character.
Ex: Spans® generally have low HLB
numbers & they are also oil soluble.
They will cause the oil phase to
predominate & form an w/o emulsion.
The higher HLB number would indicate that the emulsifier has a large number of hydrophilic groups on the molecule and therefore should be more h
HLB System
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The higher HLB number would indicate
that the emulsifier has a large number
of hydrophilic groups on the molecule
More hydrophilic in character.
Tweens® have higher HLB numbers &
also water soluble.
They will cause the water phase to
predominate & form an o/w emulsion.
HLB System

Combinations of emulsifiers can
produce more stable emulsions than
using a single emulsifier with the same
HLB number. The HLB value of a
combination of emulsifiers can be
calculated as follows:
Excercises

What is the HLB value of a surfactant
system composed of 20 g Span 20
(HLB = 8.6) + 5 g Tween 21 (HLB =
13.3)?
Methods of Emulsion
Preparation
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
Commercially, emulsions are prepared
in large volume mixing tanks & refined
& stabilized by passage through a
colloid mill or homogenizer.
Extemporaneous production is more
concerned with small scale methods.
Methods of Emulsion
Preparation
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
Several methods are generally
available to the pharmacist. Each
method requires that energy be put
into the system in some form.
The energy is supplied in a variety of
ways: trituration, homogenization,
agitation, & heat.
Continental Method
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Dry Gum, or 4:2:1 Method
Used to prepare the initial or primary
emulsion from oil, water, & a hydrocolloid or
"gum" type emulsifier (usually acacia).
The primary emulsion, or emulsion nucleus,
is formed from 4:2:1 parts of
oil:water:emulsifier. 4 parts oil & 1 part
emulsifier represent their total amounts for
the final emulsion.
Continental Method
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
In a mortar, the 1 part gum is levigated
with the 4 parts oil until the powder is
thoroughly wetted
2 parts water are added all at once, &
the mixture is vigorously continually
triturated until the primary emulsion
formed is creamy white & produces a
"crackling" sound as it is triturated,
usually 3-4 min
Continental Method


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Additional water or aqueous solutions may
be incorporated after the primary emulsion
is formed.
Solid substances: active ingredients,
preservatives, color, flavors. Generally
dissolved & added as a solution to the
primary emulsion.
Oil soluble substance: in small amounts,
may be incorporated directly into the
primary emulsion.
Continental Method


Any substance which might reduce the
physical stability of the emulsion, such as
alcohol (which may precipitate the gum)
should be added as near to the end of the
process as possible to avoid breaking the
emulsion.
When all agents have been incorporated,
the emulsion should be transferred to a
calibrated vessel, brought to final volume
with water, then homogenized or blended to
ensure uniform distribution of ingredients.
English (Wet Gum)
Method


Proportions of oil, water, & emulsifier
are the same (4:2:1), but the order &
techniques of mixing are different.
The 1 part gum is triturated with 2
parts water to form a mucilage; then
the 4 parts oil is added slowly, in
portions, while triturating.
English (Wet Gum)
Method

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After all the oil is added, the mixture is
triturated for several min to form the
primary emulsion. Then other
ingredients may be added as in the
continental method.
It is more difficult to perform
successfully, especially with more
viscous oils, but may result in a more
stable emulsion.
Bottle (Forbes) Method
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May be used to prepare emulsions of
volatile oils, or oleaginous substances
of very low viscosities.
It is not suitable for very viscous oils
since they cannot be sufficiently
agitated in a bottle.
This method is a variation of the dry
gum method.
Bottle (Forbes) Method
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
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One part powdered acacia (or other
gum) is placed in a dry bottle & four
parts oil are added.
The bottle is capped & thoroughly
shaken.
The required volume of water is added
all at once, the mixture is shaken
thoroughly until the primary emulsion
forms.
Bottle (Forbes) Method

It is important to minimize the initial
amount of time the gum and oil are
mixed. The gum will tend to imbibe
the oil, and will become more
waterproof.
Bottle (Forbes) Method
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
It is also effective in preparing an olive
oil & lime water emulsion, which is
self-emulsifying.
In the case of lime water & olive oil,
equal parts of lime water & olive oil
are added to the bottle & shaken. No
emulsifying agent is used, but one is
formed "in situ" following a chemical
interaction between the components.
Beaker Method
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
When synthetic or non-gum
emulsifiers are used, the proportions
given in the previous methods become
meaningless.
Most appropriate method for preparing
emulsions from surfactants or other
non-gum emulsifiers is to begin by
dividing components into water
soluble & oil soluble components
Beaker Method
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
All oil soluble components are
dissolved in the oily phase in one
beaker & all water soluble components
are dissolved in the water in a
separate beaker.
Oleaginous components are melted &
both phases are heated to ±70°C over
a water bath.
Beaker Method
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
The internal phase is then added to
the external phase with stirring until
reaches room temperature.
The mixing of such emulsions can be
carried out in a beaker, mortar, or
blender; or, in the case of creams &
ointments, in the jar in which they will
be dispensed.
Auxiliary Methods

Instead of, or in addition to, any of the
preceding methods, the pharmacist
can usually prepare an excellent
emulsion using an electric mixer or
blender.
Auxiliary Methods

An emulsion prepared by other
methods can also usually be improved
by passing it through a hand
homogenizer, which forces the
emulsion through a very small orifice,
reducing the dispersed droplet size to
about 5 µm or less.
HLB Values
Commercial Name
Chemical Name
HLB Value
PEG 400 Monolaurate
Polyoxyethylene monolaurate
13.1
Sodium lauryl SO4
Sodium lauryl SO4
40
Span® 20
Sorbitan monolaurate
8.6
Span® 60
Sorbitan monostearate
4.7
Span® 85
Sorbitan trioleate
1.8
TEA oleate
TEA oleate
12
Tween® 20
Polyoxyethylene sorbitan
monolaurate
16.7
Tween® 65
Polyoxyethylene sorbitan
tristearate
10.5