Industrial Pharmaceutics1

Industrial Pharmaceutics
Semester 8th
Sir. Talib Hussain

Muhammad Kafeel | 8th Semester

 Industrial Pharmaceutics2

Emulsions
“An emulsion is a dispersion of a liquid as globules in another liquid that is immiscible with the
first and the system is stabilized with the emulsifying agents, emulgent or emulsifiers.”

Diameter of Globules:
The diameter of globules usually varies about 0.1—100 µm or
-3 -3
0.1 × 10 – 100 × 10 mm.

Types of Emulsions
A stable emulsion must contain at least these components;

Dispersed phase.
Dispersion medium.
Emulsifying agent.

Invariably, one of the two immiscible liquids is aqueous and the second is oil.

1. O/W Emulsions:
An emulsion in which the oil is dispersed as droplets
throughout the aqueous phase is termed as oil-in-water (O/W) emulsion.

Most pharmaceutical emulsions designed for oral administration are of the O/W type and
require the use of an O/W emulsifying agents. Theses include synthetic non-ionic surfactants,
acacia, tragacanth and gelatin.

2. W/O Emulsions:
When water is dispersed phase and oil is dispersion medium,
the emulsion is of water-in-oil (W/O) type.

Butter and salad creams are W/O emulsions. Emulsified lotions and creams are either O/W or
W/O, depending on their use.

Emulsifying agents used are sorbitan, ester etc.

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3. Multiple Emulsions:
The dispersed phase of these emulsions contain even
smaller droplets which are miscible with continues phase.

These multiple emulsions may be;

 O/W/O type.
 W/O/W type.

In case of oil-in-water-in-oil (O/W/O) emulsions, the aqueous phase is between two oil
phases. These emulsions are better formed b lipophilic, non-ionic surfactants using gum acacia
emulsified systems.

In case of water-in-oil-in-water (W/O/W) emulsions, the internal and external aqueous

phases are separated by an oil phase. Theses emulsions are better formed by non-ionic
surfactants in a two stage emulsification procedure.

In these systems both hydrophilic and hydrophobic emulsifiers are used and both have an
effect on the yield and stability.

Multiple emulsions have been developed with a view to delaying the release of active
ingredients.

4. Micro Emulsions:
Micro emulsions are liquid dispersions of water and oil that
are made homogeneous, transparent and stable by the addition of relatively large amount of
surfactant and a co-surfactant.

Micro emulsions may be oil-in-water (O/W) or containing droplets of water in oil (W/O) types,
with diameter of about 10—200 nm and volume fraction of the dispersed phase varies from 0.2
—0.8.

Applications of Micro Emulsions:

Micro emulsions are used in such a diverse applications as;

Floor polishes.
Agricultural pesticides formulations.
Tertiary petroleum recovery.

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O/W micro emulsions are being formulated as aqueous vehicle for oil soluble drugs to
be administered by the oral or parentral routes.

Determination of Emulsion Types

It is important for pharmacist to know the type of emulsion; they have prepared or dealing
with, because this can affect its properties and performance. Unfortunately, the several
methods available can give incorrect result. So, the type of emulsion determined by one
method should always be confirmed by means of second method.

1. Dilution Test:
The dilution method depends on the fact that an O/W emulsion
can be diluted with water and W/O emulsion with oil. When oil is added to an O/W emulsion or
W/O emulsion, the additive is not incorporated into the emulsion and separation is apparent.
The test is greatly improved if the addition of water or oil is observed microscopically.

2. Conductivity Test:
An emulsion in which continues phase is aqueous can be
expected to possess a much higher conductivity than an emulsion in which continues phase is
an oil.

Accordingly, it frequently happens that when pair of electrodes connected to a lamp and an
electrical source is applied into an O/W emulsion, the lamp lights because of the passage of a
current of between the two electrodes. If the lamp does not light, it is assumed that the system
is W/O.

3. Dye Solubility Test:

This test is based on solubility of dye in external phase.
E.g. methylene blue (water soluble dye) when spread over an emulsion, if continues coloration
takes place emulsion is o/w and if patches of dye are observe then emulsion is w/o. same test
can be performed with oil soluble dye.

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Stability of Emulsions
“A stable emulsion may be defined as a system in which the globules retain their initial
character and remain uniformly distributed throughout the continues phase.”

Various types of deviation from this ideal behavior commonly are;

1. Breaking or Cracking:
This involves coalescence of the dispersed globules
and produced eventual separation of the emulsion into phases. It will occur if the barriers to
coalescence are inefficient or if they are weakened by some means.

Some of the factors that cause breaking are;

The addition of a substance that is incompatible with the emulsifier may destroy its
emulsifying ability. E.g.
The effect of large anions on cationic emulsifying agent.
The effect of Mg or Ca ions in hard water on the alkali
soaps.
The effect of phenolic substances on cetomacrogol.
An increase in temperature will increase the number of collisions between globules that
are effective in overcoming the barrier to coalescence.
An increase in temperature may coagulate certain type of macromolecular emulsifying
agent. E.g. proteins.
Freezing of the aqueous phase will produce ice crystals that may exert unusual pressure
on the oil globules. In addition, dissolved salts will concentrate in the remaining
unfrozen water and may affect electrical barriers to coalescence.
2. Creaming:
This involves the concentration of dispersed globules in either the
upper or lower layers of the emulsions. It is caused by the influence of gravity on the globules,
since they usually have a different density from that of the continues phase. If the globules
have lower density, they will tend to concentrate in upper layer of the system. This is common
in dilute O/W emulsion. The cream on milk is a familiar example.

Globules will settle to the lower layer if they have a greater density than the continues phase.
This is common in dilute W/O emulsion.

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In creaming the dispersed globules retain their identities and do not coalesce as they do in
breaking. A uniform dispersion of globules can be re-obtained by shaking the system. Creaming
is not therefore such a serious instability as breaking. However creaming is undesirable from
pharmaceutical point of view because a creamed emulsion is in-elegant in appearance, provides
the possibility of inadequate dosage and increase the likelihood of coalescence, since the
globules are closer together in the cream.

The main factors utilized in reducing the rate of creaming in pharmaceutical emulsions are;

Reduction in mean globules diameter. This is usually achieved by using an efficient

homogenizer.
Increase in viscosity of continues phase by using thickening agents. For example
tragacanth and methylcellulose for O/W emulsions and soft paraffin for W/O emulsions.
Storage at low temperatures. Freezing the aqueous phase should be avoided since this
may cause breaking of the emulsion.
3. Flocculation or Coagulation:
This involves globules aggregating into
loose masses within the emulsion. The globules do not coalesce and may redistribute o shaking.
Thus, flocculation is less serious than breaking.

Formation of emulsion
Emulsion are not prepared spontaneously but requires a dispersion method with a sequence of
processes.

 For breaking up the internal phase into droplets.

 Stabilizing them in the external phase .

The complete process is designed in such a way that both steps are carried-out before internal
phase coalesce.

 The breakup of internal phase is rapid and stabilizing step & rate of coalescence are
time & temperature dependant.
 So for the formation of emulsions suitable physical & chemical parameters are selected
&controlled to favor emulsion formation.

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Physical Parameters:
The reduction of internal phase into droplets required
application of energy in the form of heat, mechanical agitation, ultrasonic vibration or
electricity etc.

 The amount of work (done) input depends on length of time during which energy is
supplied. Thus timing during which work input is schedule become another important
parameter.
1. Heat:
(Have 2 methods)

1; condensation method 2: dispersion method

a) Condensation Method:
The bonds b/w molecules of liquid can be easily broken by vaporization,
So the prepared emulsion vapors of internal phase is passed through external phase
that contain suitable emulsifying agent,
This process is slow & limited to the preparation of dilute emulsions having low vapor
pressure.
b) Disperse Method:
Practically emulsification is more favorable by dispersion affected by
Heat or change in temp.
An increase in temp results in decrease viscosity. So emulsification is favored by
increase in temp.
At the same time on increase in temp will raise the kinetic energy of droplet &
facilitate coalescence.
This type of instability is observed when emulsion is stored at elevated temp for
longer period of time.
Change in temp. alter the distribution coefficient of emulsifiers b/w two phases &
cause emulsifier migration
But this distribution of emulsifier caused by temp Change doesn’t correlate directly
with emulsion formation or stability although changes in surface tension & viscosity
occur simultaneously.
2. Phase inversion temp ; (PIT)
Inversion of emulsion type is the major influence of temp on emulsion.
When w/o emulsion of benzene in water being stabilized by sodium stearate invert to
o/w upon heating & reform w/o emulsion upon cooling.
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The temp at which inversion occur is called phase inversion temp. & depends on
emulsifier concentration.

As emulsion is usually prepared at relatively high temp & then allow to cool at room temp
favors this inversion.

Emulsion prepared by PIT is generally stable & believe to contain finely divided dispersed
phase.

 PIT is generally considered the temp. at which hydrophilic & lipophilic properties of
emulsifier are in balance & is therefore called HLB temp.

Shinoda’s description of processes:

An o/w emulsion stabilized by a non-ionic polyoxyethylene

derived (ether) surfactants contains oil swollen micelles of surfactants as well as emulsified oil,
the water solubility of ether type surfactant is due to formation of hydrogen bonds b/w water
& O-atom of ether. when temp. increases water solubility decreases as hydrogen bond are
broken at elevated temp. called as cloud point. So as water micells are broken & size of
emulsified oil droplets being to increase.

The continuous rise in temp. cause separation into an oil phase , a surfactant phase & water , so
it is near this temp. that water insoluble surfactant being to form w/o emulsion containing both
water swollen micelles & emulsified water droplet in a continuous oil phase.

3. Timing:
Timing also exerts marked & complex influence on process of emulsification

 Initial agitation during emulsification form droplets however continuous agitation

increases the chances of collisions b/w droplet & coalescence can occur
 So it is advisable to avoid excessive shaking during & after emulsification. As it is
impossible to specify the time period of agitation required for emulsification

Baiggs describe process; two immiscible liquids are mixed in presence of emulsifying agent &
shake until emulsion is formed, he showed that best way to make emulsion is intermittent
shaking.

 Benzene 60% can be emulsified in 1% aq.sodium oleate by mechanical shaking 750

times during 4-5min.

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 The same mixture can be emulsified in nearly fine hand shakes in 2min. if emulsion is
allowed to stand for 20-30sec. after each shake.

The reason for this time dependent droplet stabilization is distribution of emulsifier b/w two
phases, slow formation of clerical double layer on benzene droplet surface, or interruption of
droplet formation by continuous shaking.

 Timing & scheduling also affect the speed at which two immiscible liquids are blended
e.g. in o/w emulsion the rate at which oil phase is added to aqueous phase affect
particle size & ultimate stability of finished emulsions.
4. Low energy emulsification ; (Lin’s process)
Classical procedure of emulsification requires considerable expenditure of energy during both
heating & cooling cycle of emulsion formation.

In low energy emulsification all of the internal phase & only a portion of external phase
are heated. After emulsification of the heated portion, the remainder of external phase
is added to emulsion concentrate or pre-formed concentrate is blended into continuous
phase

In those emulsions in which PIT arise emulsification is done above PIT, which results in
emulsions with externally small droplet size.

 So by careful control of variables (emulsification temp., mixing intensity, the amount of

external phase employed during emulsification, method of blending) it is possible to
prepare emulsion of smaller and more uniform particle size than those resulting from
conventional process.

Muhammad Kafeel | 8th Semester