Pharmaceutics I Emulsion & Dr.

Hana Amr FaYed

Emulsion
Phase inversion
Principles: the reversal of the emulsion type from O/W to W/O or the reverse

Result: The resulting emulsion has properties different from those of the original system

Examples:

Univalent soap such as (Sodium oleate) give O/W emulsion  reversed to a W/O emulsion by the
addition of electrolyte Such as (Calcium chloride)

Determination of emulsion type

1. Dilution
2. The dye solubilization method
3. Electrical Conductivity
4. Appearance
5. The filter paper wetting

1. Dilution

Method: placing a little of emulsion in water

Result:

a) If the emulsion is readily dispersing  it is O/W

b) If Not Disperses  it is W/O

2. The dye solubilization method

 Methylene blue give blue color in O/W emulsion

 Sudan III & Scarlet red gives red color in W/O emulsion
3. Electrical Conductivity
O/W emulsion conduct the electric currents, as water is ionizable

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
W/O emulsion doesn’t conduct the electric currents, as Oil is non-ionizable

4- The filter paper wetting method

Method: Drop of emulsion is placed on filter paper

If the external phase is spread quickly  this o/w and dry if exposed to air
While w/o emulsion stain the filter paper and doesn't dry

5- Appearance

O/W emulsion has a milky white appearance

W/O emulsion has a waxy yellow appearance

Experiment O/W W/O

The dilution method Dispersed or spread Not dispersed
Dye method
A) Methylene blue Blue -----
B) Scarlet red ------- Red
Electrical Conductivity Conduct Not conduct
Filter paper or Spreading Stain filter paper
wetting method Drying to air Not dispersed
Not dry
Appearance Milky white Waxy yellow

Methods of emulsion preparation.

For Mineral oil

1. The continental or dry gum method
 Used in preparation of mixture of a
part of fixed oil and part of volatile oil

2. The English or wet gum method For Fixed Oil

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
It is used for the preparation of emulsion
from:
3. The bottle or the Forbes bottle
- volatile oil
method
- oleaginous substances of low viscosities
- Not suited for viscous oils

Method:

1. Powdered acacia is placed in a dry bottle

2. 2 parts of oil are then added and the mixture is thoroughly‫ تماما‬shaken in the capped
container
3. A volume of water added in portions, the mix. Being thoroughly shaken after each
addition
4. When all water has been added, the primary emulsion thus formed may be diluted to the
proper volume with water or an aqueous solution of other formulate agents

Emulsion stability

- Characters of a stable emulsion

1- Absence of flocculation and creaming
2- Absence of coalescence and breaking of emulsion
3- Absence of microorganisms
4- Elegant and good appearance, odor, color and consistency
1. Flocculation and creaming

The joining together of globule to form large clumps of floccules which rise or
settle in the emulsion more rapidly than do the individual particles
Flocculation
Or: light, fluffy conglomerates that are held together by weak van der Waals
forces.

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
The rising (upward creaming) or settling (downward creaming) of globules or
- Creaming floccules to form a concentrated layer at the surface or the bottom of the
emulsion (such as milk)
Creaming results in: (Disadvantages)
l. Affect the appearance of emulsion
2. Lack of the uniformity of the product
3. Variation in the amount of drug administered
Factors affecting stability of emulsion
A Stock's equation included the various factors involved in the creaming processes
𝒅𝟐 (𝑷− 𝑷𝟎) 𝒈
V= 𝟏𝟖 𝝁

V𝛼d
V𝛼 (p-p0)
1
V𝛼
𝜇

Where: V= the velocity of the fall of a sphere particle ‫سرعة الترسيب‬

Internal phase ‫ كثافة ال‬P= the density of the sphere (internal)
Po= the density of the sphere (external)
g = the gravity force ‫عجلة الجاذبية‬
μ = the viscosity of the dispersion medium ‫لزوجة الوسط‬
‫) ؟ قالك هنشتغل على العالقات اللي فوق دي‬V( Creaming ‫يبقى ازاي اقلل ال‬
So, how can we reduce the tendency of the emulsion for creaming?
1-Globule size Reduce the particle size by using homogenizer decrease the velocity
of creaming
2-The density of the internal and external phase
When the density of the internal phase and external phase equal, the velocity of creaming
is zero, in this case not form emulsion but form solution with one phase.
When the density of the internal phase is less than external phase

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
 So, V= - ve the creaming occurs in an upward direction
 Occur in o/w emulsion
When density of the internal phase is denser than the external phase
 So, V= + ve the creaming occurs downward
 Occur in w/o emulsion
3-The gravity is constant
 Viscosity  rate of creaming
The velocity of creaming is inversely proportional to the viscosity of the
4- The viscosity external phase of the emulsion
 Auxiliary emulsifiers such as: agar - methyl cellulose added to
improve the consistency the emulsion

P=P0 V= Zero Stable Emulsion

P<P0 V= -ve Upward creaming O/W
P>P0 V=+ve Downward creaming W/O

2- Coalescence and breaking

Creaming Breaking (cracking)

Reversible Irreversible

Because the globules are still surrounded by a While in emulsion which has broken in which
protective sheath of emulsifying agent and the phase has separated as distinct layers
may be redispersed by agitating the product simple mixing fails to re-establish the stable

𝒅𝟐 (𝑷− 𝑷𝟎) 𝒈
emulsion.
V=
𝟏𝟖 𝝁
The emulsion may be reconstituted only by
incorporating more emulsifying agent and
passing the product through a homogenizer

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
Causes of cracking of an emulsion

a- Addition of emulsifying agents of opposite types

1- Addition of monovalent soap to divalent or divalent to monovalent soap emulsifying agent
2- Anionic and cationic emulsifying agents are incompatible
b- Decomposition or precipitation of emulsifying agent
1- Alkali soaps are decomposed by acid so, acids cause cracking of soft soap emulsion
2- Electrolytes e.g. NaCl cause cracking where monovalent soaps are salted by NaCl
3- Phenols are incompatible with nonionic emulsifying agents
4- Alcohols precipitate gums, proteins, and gelatin because they are insoluble in alcohol
c- Addition of common solvent
Addition of a liquid in which both dispersed and continuous phases are soluble forms a one-
phase system and destroys the emulsion

e.g. castor oil, soft soap and water

They all are soluble in alcohols so, addition of sufficient amount of Alcohol to the
emulsion produce clear solution (no emulsions)

d- Creaming
It is undesirable because the coalescence of the globules in the cream favors the breakdown of
the interface
e- phase-volume ratio:
-If the dispersed phase concentration in excess of 74 % have unmarked tendency to crack
-The more stable emulsions are those having a phase volume of 50/50

3- Deterioration by microorganisms

Such as: mould, yeasts and bacteria lead to:

1- Decomposition of the emulsifying agent
2- Contaminate the aqueous phase
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3- Rancidity in the oil and destroy oil soluble vitamins.
So, system can be protected against micro-organism by using
(a) Benzoic acid
(b) High conc. Of alcohol
(c) Salicylic acid
(d) combination of:
- Para hydroxy benzoate 0.1%
- Methyl ester 0.2% (Soluble in water)
- Propyl ester 0.02% - 0.05% (Not soluble)

The ideal Characters of preservatives:

1- Low toxicity
2- Stability to heat and storage
3- Low cost, acceptable taste, odor and color
4- Effective against a variety of organisms
N B: Complex problems arise whenever the preservative interacts with one of the emulsion
ingredients such as interaction makes the preservative unavailable

Example
Phenolic preservative interacts with compounds containing poly oxy ethylene groups which
interact with preservative efficiency.
So, to compensate ‫تعويض‬for the loss of preservative by interaction an amount equal to the
complexed material may be added

4- Miscellaneous physical and chemical changes

Emulsion can be deteriorated by:

1. Light
2. Extreme temperature
3. Oxidative

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
4. Hydrolytic rancidity of the oil.

Light and rancidity affect the color and odor of oils and destroy their vitamin activity
therefore:

1- To prevent the rancidity: antioxidants are necessary Such as

 Butylated hydroxyl Anisole (BHA)
 b) Butylated hydroxyl toluene (BHT) in conc. (0.001-0.1 %)
2- Emulsions should be kept in tight containers and Stored at moderate temperature
3- If affected by light, they should be stored in dark bottles

Factors should be taken in during emulsion preparation

a) Soap is not used as an emulsifier a system having a final pH 5 (below 5)

Chemical stability b) Easily hydrolyzed ester is not used in an emulsion which is either acid
or alkaline
Lipid may be natural or synthetic the consistency of these lipids ranges
Choice of lipid phase
from mobile liquid to hard solid
It is the ratio of the internal phase to the external phase

Phase ratio

Choice of the Three broad classes of emulsifying agent

emulsifying agents EX: the surfactants - the hydrophilic colloids - finely divided solids
This depends on the HLB. Where in case of o/w emulsion type stable
Choice of surfactants emulsion can be prepared by combination of a lipophilic and hydrophilic
surfactant
Choice of auxiliary EX: agar, pectin, used to increase the viscosity of emulsion
emulsifiers

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
The building up of viscosity in a prepared emulsion requires some time
Consistency It is recommended that a formulated emulsion will be allowed to 24-48
hours
Due to the presence of carbohydrates, proteins and phosphatides which
Choices of an support the growth of microorganisms
antimicrobial
preservative It is necessary to prevent contamination by using uncontaminated raw
material and carefully cleaning equipment
-Butylated hydroxyl anisole (BHA)
Choice of antioxidant
- Butylated hydroxyl toluene (BHT)

Special emulsion systems

Example:

1-Multiple emulsions 1. if drug has bad taste and has lipophilic characters give
(W/O/W)  Water in oil in water
=Dual=Double
2. if drug has bad taste and has hydrophilic characters give
(O/W/O)  Oil in water in oil
1. Droplet size is 10-200 nm
2. Transparent
3. Expensive
2-Micro emulsions
4. More stable surfactant and co surfactants as emulsifying
agent
5. Finely divided

3-Nano particles They are similar in size and shape to micro emulsion

Assessment of emulsion shelf life

1) Aging and temperature

Storing them for varying periods of time at temperature that are higher than those
normally encountered
It would be stable at 40-45 °C but not to 50- 60 °C

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Pharmaceutics I Emulsion & Dr. Hana Amr FaYed
Place the emulsion between (4 -45 °C) at high temp.
1- Increase the rate of coalescence or creaming
2- Viscosity of emulsion become thinner (creaming)
At room temperature the emulsion more thicker
3- Freezing can damage emulsion more than heating
Due to the solubility of emulsifiers, both in lipid and aqueous phases in more sensitive to
freezing than worming
2) Centrifugation

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