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Em
Defin ul
itio si
n: on
An emulsion is thermodynamically unstable system consisting of at least two immiscible
liquid phases, one of which is dispersed as globules in the other liquid phase.
. The system is stabilized by the presence of an emulsifying agent.
. Disperse phase internal phase
.Continuous phase external phase
Consistency:
Either the disperse phase or the continuous phase may range from that of a mobile liquid
phase to a semi solid.
* Particle diameter of the dispersed phase:
* Generally: (0.1 - 100 micro m)
* in some preparations (0.01 - 100 micro m )
Applications:
* Pharmaceutical and cosmetic applications.
* Pharmaceutical applications.
* . Patient acceptance.
* Medicinal agents objectionable taste.
* More palatable for oral administration.
* Minearal oil - based laxatives.
* Oil - soluble vitamins.
* High - fat nutritive preparations.
Commonly administered as O/W emulsions .
* More efficient orally administered emulsions .
EX: absorption or bioavailability
* Patient acceptance topical y applied drugs
Types:
* Oil - in - water (O/W) emulsion
* Water - in - oil (W/O) emulsion
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O/W W/O emulsion ----------- inversion

W/O O/W emulsion ---------- inversion
* Multiple emulsions :_
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Oil in water in - oil (O/W/O) emulsion
Water in oil in water (W/O/W emulsion)
Multiple simple
W/O/W emulsion O/W emulsion
* Particle size of the disperse phase determines the appearance of an
emulsion.
* In an opaque, usually white, emulsion 0.25 - 10 mcm.
* In a transparent emulsion <120 nm .
Practical definitions:
* Usually one phase persists in droplet from for a prolonged period of time
Internal (dispersed) phase.
* An assembly of close - packed mono disperse spherical droplets, as the internal
phase can occupy no more than approximately 74% of the total volume of an
emulsion.
* An emulsifier I operationally defined as a stabilizer of the droplet form (globules) of
the internal phase.
* On the basis of their structure :
Emulsifiers (wetting agent or surfactants) may be described as molecules comprising
both hydrophilic (oleophobic) and hydrophobic (oleophilic) portions.
Amphiphilic (EX:_ water - and - oil loving) .
* The term emulsion should be limited to liquid - in - liquid system.

Formulation of emulsion
* Preparation of emulsion by the commonly employed method.
Breaking up the internal phase droplets.
Stabilizing them in the continuous phase.
Dependent on the time + temperature.
* Physical + chemical parameters
Selected
Controlled
Physical parameters:
* The application of energy:
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Is required to reduce the internal phase into smal droplets.

1. Condensation method:
- heat
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- Vaporization is an effective way of breaking almost al bonds between the molecules
of a liquid.
- Passing the vapor of a liquid into extend phase that contains suitable emulsifying
agents emulsion.
2. Emulsification by dispersion:
* Effect by change in temperature.
* Increase T ? (Unpleasant effect due to separation) favor
emulsification or coalescence.
* Storage
* Changes in T emulsifier - migration.
3. Phase inversion technique:
Benzene + water + sod. Stearate W/O emulsion
W/O emulsion Heating O/W emulsion
W/O emulsion cooling O/W emulsion
* PIT (phase inversion temperature):
- Is the temperature at which inversion occurs
- Depends on emulsifier concentration
- Can occur during the formation of emulsion
* This technique produces quite stable emulsion which contains a finely dispersed
internal phase
PIT :
- Is the temperature at which the hydrophilic and the lipophilic properties of the
emulsifier are in balance
- It is also called the HLB temperature
An O/W emulsion: polyoxyethylene - derived surfactant contains oil - swollen micelles of
the surfactant emulsified oil.
* Temp. water - solubility of surfactant
- Micelles are broken
- Size of emulsified oil droplets begins to
* A continued Temp. causes separation into :
Oil - phase, surfactant phase, and water
* Near this temperature :
The now water - insoluble surfactants begins to form a W/O emulsion containing both :
- Water - swollen micelles +
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- Emulsified water droplets in a continuous oil phase

* Timing
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Formulation of emulsion:
A. Oil phase
B. Aqueous phase (AQ)
C. Emulsifiers
A- Oil phase: - A variety of oils vegetable ails or mineral oils
4. Additives:
- Buffers (phosphates, carbonate, acetate buffers) - Flavors
- Preservatives (parapens) - Colors ( acceptance, mask of bad colors
-Antioxidants (ascorbic acid, satiric acid, vit.E) of ingredient, identification of product)
- Perfumes - Humectants
- sweetening agents (sorbitol, sucrose (dental, diets, diabetes) glucose, saccharin)
A-Drug:
The oil phase itself active ingredient (drug)
EX: mineral oil, castor oil O/W emulsion for oral administration
A drug dissolved or dispersed in either the oil or aqueous phase of an emulsion which serves
as a vehicle.
i-
Hydrocarbone: mineral oils, petrolatum, polyethylene waxes.
ii-
Esteras: vegetable oils, animal fats , lanolin
iii-
Alcohols: long - chain (natural and synthetic)
iv-
Fatty acids: long - chain (natural and synthetic)
B- Aqueous phase:
* Water
* Any water soluble ingredient
C- Emulsifiers:
I-
Nonionic surfactants
II-
Ionic surfactants
a- Anionic surfactants
b- Cationic surfactants
Emulsifying agents assist in the formation of emulsions by three mechanisms:
1. Reduction of interfacial tension - thermodynamic stabilization
2. Formation of rigid interfacial film - mechanical barrier to coalescence
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3. Formation of an electrical double layer - electrical barrier to approach of particles



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Table 4: HLB values of selected emulsifiers
Chemical designation
HLB
Water dispersibility
Ethylene glycol distearate
1.5
No dispersion
Sorbitan monostearate
4.7
Poor dispersion
Polyoxyethylene (4)
9.6
Milky dispersion
Sorbitan monostearate
(stable)
Polyoxyethylene (20)
14.9
Clear solution
Sorbitan monostearate

Table 5: HLB values required by commonly used lipids

Oral emulsion (O/W):
(A):
* Cottonseed oil, winterized 460.0g
* Sulfadiazine 200.0g
* Sorbitan monostearate 84.0g
(B):
* Polyoxyethylene 20 sorbitan
* Mono stearate 36.0g
* Sodium benzoate 2.0g
* Sweetener q s
* Water potable 1000.0
(C):
* Flavor oil q s
Procedure:
1. Heat (A) to 50C0 and pass through col oid mil
P
P
2. Add (A) to 50C0 (B) at 65C0 and stir while cooling to 45C0
P
P
P
P
P
P
3. Add (C) and continue to stir until room temperature is reached
Equipment:
A - Special equipment:
- Mechanical stirrers - Ultra sonifiers
- Homogenizers - Colloidal mills
See other equipment in suspension
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Procedure:
1. The components of the oil or fat mixture are melted and mixed in a stain less steel

steam - jacketed kettle
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2. The components of the aqueous phase are dissolved in purified water and filtered ,
The solution may be heated to a temperature
3. A soluble drug may be added to the aqueous phase at this time
4. The oil phase is transferred by gravity or pump to the emulsion mixing kettle , whose
walls have been heated to the temperature of the oil phase
5. The aqueous phase is added slowly to the oil phase and mixed at a temperature of
the oil phase and mixed at the temperature of 70C0 until the formation of the
P
P
emulsion
6. The temperature of the cooling medium in the kettle jacket should be decreased
gradually and at a rate consistent with the mixing of the emulsion
7. If the drug is thermo labile
* It (Drug) is added in a solution form or as crystals into the cooled (R.T) emulsion
provided that it is soluble in the external phase
* Adjustment of the final water content of a W/O emulsion is not easy once the
emulsion has been formed
* Heating viscosity of the system enable shear forces to be transmitted
through the product more easily
* Continue stirring during cooling to avoid demulsification
* When the system (emulsion) reach room temp. , volatile ingredients (flavors ,
perfume ) can be added
* Alcoholic solutions and electrolytes :
Influence the physical stability of the emulsion requires to be diluted as much
as possible before adding slowly and with constant mixing.
Evaluation and QC: see the practical part
5. Manufacturing problems:
- Coalescence (breaking, cracking)
- Creaming
- Flocculation
- Foaming
- Others
Stable emulsions
A- Stable emulsion: is an emulsion in which the dispersed globules retain their initial
character and remain uniformly distributed throughout the continuous phase.
Emulsifying agent form an interfacial film around the dispersed droplet
Symptoms of instability:
Drug storage, emulsions in stability is evidenced by:
i- Creaming,
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ii- Reversible aggregation (flocculation) , and / or
iii- Irreversible aggregation (coalescence)

6. Coalescence (breaking, cracking)
Separation of the emulsion into it is constituent phases
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Factors cause an emulsion to crack:
1. Addition the chemical that is incompatible with the emulsifying agent , thus
destroying its emulsifying ability.
2. Bacterial growth.
3. Temperature change.
- Increase in T :
Denaturation protein emulsifying agent
Change solubility of non - ionic emulgent
* Heating above 70C0 destroys most emulsions
P
P
* Freezing crack emulsion (separation)
7. Creaming:
Is the separation of an emulsion into two regions one of which is richer in the disperse phase
than the other.
EX: creaming of the milk when fat globules slowly rise to the top of the product
* It is not serious instability problem
* Shaking the emulsion uniform dispersion
* Undesirable increase like hood of coalescence of the droplets
* Inelegant
* Risk of the patient obtaining an incorrect dosage
Methods of reducing creaming
1- Production of an emulsion of same droplet size
2- Increase in the viscosity of the continuous phase
3- Reduction intensity difference between the two phases
4- Control of disperse phase concentration
Flocculation:
Flocculation involves the aggregation of the dispersed globules into loose clusters within the
emulsion.
The individual droplets retain their identities but each cluster behaves physically as a single
unit (increase creaming rate)
As the flocculation must precede coalescence any factor preventing or retarding flocculation
would therefore maintain the stability of the emulsion
Flocculation
secondary minimum
Primary minimum
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The presence of a high charge density on the dispersed droplets high energy barrier



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Reduces the incidence of flocculation in the primary minimum
Emulsion stability assessment:
- Aggregation (Flocculation) - Coalescence - Phase separation
Stability testing of emulsions
Methods of assessing stability:
1- Macroscopic examination :
* Examination of degree of creaming or coalescence occurring over a period
of time.
* By calculating the ratio of (V) of creamed (separated) part / total V of
emulsion, and compare the values for different products.
2- Globules size analysis :
If mean globule size with time (No. of globules decreases)
Cause Coalescence
Therefore, it is possible to compare rates of coalescence for a variety of emulsion
formulations.
A- Microscopic method
B- Electronic particle counting devices :
I-
Coulter counter
II-
Laser diffraction sizing
3- Viscosity changes :
* Factors viscosity of emulsion
* Any variations in globule size or number or in orientation or migration of
emulsifier over a period of time
May be detected by a change in apparent viscosity
Accelerated stability testing:
1. Storage of adverse temperature :
* Subjecting an emulsion to extreme variation in temperature effective
way of assessing its physical stability.
* Temperature cycling method.
2. Centrifugation :
- Centrifuge at 200 - 300 rpm
- Accelerates the rate of creaming

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Document Outline

• Definition:
  • Consistency:
  • Applications:
  • Types:
  • Practical definitions:
  • Formulation of emulsion
  • Physical parameters:
  • Formulation of emulsion:
  • Procedure:
  • Equipment:
  • Procedure:
  • Stable emulsions
    • Symptoms of instability:
    • Factors cause an emulsion to crack:
    • Methods of reducing creaming
    • Stability testing of emulsions
    • Accelerated stability testing:

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