Pharmaceutical emulsions

1. PHARMACEUTICAL EMULSIONS
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2. EMULSION
Emulsion may be define as the thermodynamically unstable system
consisting of two immiscible liquid phases in which one phase is dispersed
as globules throughout the other phase and system being stabilized by the
emulsifying agent.
Once the desire emulsion and emulsifier has been selected then consistency
is considered which maintain the stability and flow properties of the
emulsion.
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3. TYPES OF EMULSIONS
Simple emulsions (Macro emulsions)
Oil-in-water (O/W)
Water-in-oil (W/O)
Multiple emulsions
Oil-in-water-in-oil (O/W/O)
Water-in-oil-in-water (W/O/W)
Micro emulsions
Nanoemulsions
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4. DETERMINATION OF TYPE OF
SIMPLE EMULSION
Dilution test
In this test the emulsion is diluted either with oil or water. If
the emulsion is o/w type and it is diluted with water, it will
remain stable as water is the dispersion medium" but if it is
diluted with oil, the emulsion will break as oil and water are
not miscible with each other. Oil in water emulsion can easily
be diluted with an aqueous solvent whereas water in oil
emulsion can be diluted with a oily liquid
Dye solubility test
In this test an emulsion is mixed with a water soluble dye
(amaranth) and observed under the microscope. If the
continuous phase appears red, it means that the emulsion is
o/w type as water is in the external phase and the dye will
dissolve in it to give color. If the scattered globules appear
red and continuous phase colorless, then it is w/o type.
Similarly if an oil soluble dye (Scarlet red C or Sudan III) is
added to an emulsion and the continuous phase appears red,
then it is w/o emulsion.
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5. DETERMINATION OF TYPE OF
SIMPLE EMULSION
Conductivity Test:
The basic principle of this test is that water is a good conductor of electricity.
Therefore in case of o/w emulsion, this test will be positive as water is the external
phase. In this test, an assembly is used in which a pair of electrodes connected to an
electric bulb is dipped into an emulsion. If the emulsion is o/w type, the electric bulb
glows.
(a) o/w type emulsion (b) w/o type emulsion
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6. DETERMINATION OF TYPE OF
SIMPLE EMULSION
Cobalt Chloride Test:
When a filter paper soaked in cobalt chloride solution is
dipped in to an emulsion and dried, it turns from blue to
pink, indicating that the emulsion is o/w type.
Fluorescence Test:
If an emulsion on exposure to ultra-violet radiations
shows continuous fluorescence under microscope, then
it is w/o type and if it shows only spotty fluorescence,
then it is o/w type.
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7. PHARMACEUTICAL
APPLICATIONS OF
EMULSIONS
 Oral products
 It covers the unpleasant taste
 Increases absorption rate
 O/W Parenteral use emulsion
 i/v lipid nutrients
 Topical use :
 Washable
 Acceptable viscosity
 Less greasy
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8. PHARMACEUTICAL
APPLICATION
Basically, both macro and micro emulsions are generally
well documented as carriers for hydrophilic and lipophilic
drugs. Meanwhile , such system increase the solubility
and bioavailability of therapeutic drugs as well as the
ability to favor the topically transport of hydrophilic
drugs. Multiple emulsions especially W/O/W are
admirable candidates for controlled and sustained
release of drugs.
Micro emulsions are isotopic mixtures of oil , water
,surfactant often with co surfactant. Micro emulsion
improve drug solubilization and bioavailability.
Meanwhile, they act as potential drug delivery system by
integrating a wide variety of drug molecules.
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9. FORMULATION COMPONENTS
The ingredient of any pharmaceutical or cosmetic
emulsion must conform to various requirements. There
are situations in which certain oils ,emulsifiers and other
ingredients must be avoided or used exclusively.
Lipid Phase:
For pharmaceutical and cosmetic products the oil phase
includes the wide variety of lipids of natural and
synthetic origin e.g plant wax( candelilla , mineral oils,
petrolatum, synthetic includes i-propylmyristate etc.
A drug in an emulsion type of dosage form distributes
itself between the oil phase and the aqueous phase in
accordance with its oil/water partition coefficient.
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10. FORMULATION COMPONENTS
Phase Ratio
The ratio of the internal phase to the external phase is
frequently determined by the solubility of the active
ingredient , which must be present at a
pharmacologically effective level.
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11. ADDITIVES FOR FORMULATION
OF EMULSIONS
1. Emulsifying agents
2. Auxiliary emulsifiers.
3. viscosity modifier
4. Antimicrobial preservatives
5. Antioxidants
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12. EMULSIFYING AGENTS
Emulsifying agents
An emulsifying agent is any material that enhances the
stability of an emulsion (i.e. Prevention of coalescence
and reducing creaming). The ideal emulsifying agent is
colorless, odorless, tasteless, non- toxic, non-irritant
and able to produce stable emulsions at low
concentrations.
They are classified into three broad classes
1 Surfactants
2 Hydrophilic colloids
3 Finely divided solids
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13. EMULSIFYING AGENTS
Selection criteria of emulsifying agents
They are selected on the basis of required “shelf life”
stability,
the type of emulsion desired, and emulsifier cost
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14. SURFACTANTS
Surfactants
Substance having both hydrophilic and hydrophobic
regions in their molecular structures are called surface
active agents or surfactants. These materials are soluble
in both water and oil. Upon addition of the surfactants
into the dispersed system the hydrophilic and
hydrophobic groups orient themselves in a
monomolecular layer facing the polar and non polar
solvents respectively.
Surfactants diffuse from the solution onto the interface
where adsorption and accumulation take place.
Interfacial tension must be lowered for the interface to
expand, if interfacial tension decrease sufficiently , the
dispersed system readily be emulsified.
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15. CLASSIFICATION OF
SURFACTANT EMULSIFYING
AGENTS
Anionic
Widely used surfactants, negatively charged in an aqueous
solution, e.g Sulphates ( sodium lauryl sulphates) , Soap (
sodium oleate), benzene sulphonate ( sulphonate sodium).
Cationic
They are positively charged in an aqueous solution e.g
quaternary ammonium and pyridinium. They are expensive.
They also utilized as preservatives, for sterilizing the
contaminated surfaces and emulsion as they posses
bactericidal action.
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16. CLASSIFICATION OF
SURFACTANT EMULSIFYING
AGENTS
Non-ionic surfactants
They are consist of (CH2CH2O)n OH or OH as the
hydrophilic group and exhibit a variety of hydrophile-
lipophile balance (HBL)which stabilize o/w and w/o
emulsions. Because of their low irritation and toxicity
non-ionic surfactants are used for oral and parenteral
formulations e.g Polysorbate 20 or Tween 20, Sorbitan
esters ( Spans)
Ampholytic surfactants
They are possess both cationic and anionic groups in
the same molecule and are dependent on the pH of
the medium. Lacithin is used for parenteral emulsions.
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17. CLASSIFICATION OF
HYDROCOLLOID
EMULSIFYING AGENTS
 Polymers that are water sensitive ( swellable or soluble) have
some utility as primary emulsifier
 Natural
 From plant origin
 Polysaccharides ( Acacia, tragacanth, agar, pectin, lecithin)
 From animal origin
 Proteins ( Gelatin)
 Lecithin
 Cholesterol
 Wool fat
 Egg yolk
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18. FINELY DIVIDED SOLIDS
Finely divided solids have been shown to be good
emulsifiers, especially in combination with surfactants
and /or macromolecules that increase viscosity e.g polar
inorganic solids such as heavy metal hydroxides, certain
non-swelling clays and pigments. Even non polar solids
carbon or glyceryl triesterate can be used.
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19. AUXILIARY EMULSIFIER
Auxiliary (Secondary) emulsifying agents include
those compounds that are normally incapable
themselves of forming stable emulsion. Their main
value lies in their ability to function as thickening
agents and thereby help stabilize the emulsion.
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20. AUXILIARY EMULSIFYING AGENTS
EXAMPLES
Product Use
Cetyl alcohol Lipophilic thickening agent and stabilizer for
o/w lotions and ointments.
Glyceryl mono stearate Lipophilic thickening agent and stabiliser for
o/w lotions and ointments.
Methyl cellulose Hydrophilic thickening agent and stabiliser
for o/w emulsions , weak w/o emulsions.
Sodium
carboxcymethyl
cellulose
Hydrophilic thickening agent and stabiliser
for o/w emulsions ,
Stearic acid Lipophilic thickening agent and stabilizer for
o/w lotions and ointments. Forms a true
emulsifier when reacted with alkali.
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21. VISCOSITY MODIFIER
Once the desired emulsion and emulsifier have been
chosen , a consistency that provides the desired stability
and yet has the appropriate flow characteristics must be
attained. The viscosity of an emulsion can be altered by
manipulating the composition of the lipid phase, by
variations in the phase ratio and the surfactant and by
addition of gums. The use of gums, clays and synthetic
polymers in the continuous phase of emulsions is a
powerful tool for enhancing an emulsion’s stability.
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22. ANTIMICROBIAL
PRESERVATIVE
Microbial contamination may occur during the
development or production of an emulsion and its use.
Frequently, the microbial contamination can arise from
the use of impure raw material or from poor sanitation
during preparation. A preservative or r a system of
preservatives can protect the emulsion from all of the
these possibilities. A preservative must has low toxicity,
stability to heat and storage , chemical compatibility,
reasonable cost and acceptable taste, odour and colour.
The examples includes, benzoic acid and salts, alcohols,
aldehydes , phenolics etc.
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23. ANTIOXIDANT
Many organic compounds are subject to autoxidation
upon exposure to air, and emulsified lipids are
particularly sensitive to attack. Many drugs are
incorporated into emulsions are subject to autoxidation
and resulting decomposition.
Upon autoxidation, unsaturated oils such as vegetable
oils, give rise to rancidity with the resultant unpleasant
odour, appearance and taste. To prevent this process
antioxidants are used. The choice of a particular
antioxidant depends on its safety, acceptability for a
particular use , and its efficacy. Antioxidants are
commonly used at concentrations ranging from 0.001 to
0.1%(w/v). The examples of antioxidants include,
Butylated hydroxyanisole(BHA), Butylated
hydroxytoluene( BHT), L-tocopherol and alkyl gallates
are particularly popular in pharmaceutical and cosmetics.
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24. EMULSIFICATION
TECHNIQUES
Laboratory scale preparation techniques
Large scale preparation techniques
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25. EXTEMPORANEOUS
(LABORATORY SCALE )
METHOD OF PREPARATION
For the laboratory scale or prescription department
emulsification of fixed/volatile oils, the most
frequently used equipment's are Wedgwood or
porcelain mortars and pestles
Continental or dry gum method
Wet gum method
Bottle or Forbes bottle method
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26. DRY GUM METHOD (
CONTINENTAL METHOD)
The continental method is also referred
to as the 4:2:1 method because of
every 4 parts by volume of oil, 2parts
of water and 1 part of gum are added
in preparing the initial or primary
emulsion.
Fixed oil = 4:1:2
Mineral oil = 3:1:2
Volatile oil = 2:1:2
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27. DRY GUM METHOD (
CONTINENTAL METHOD)
 In a mortar gum ( acacia) is levigated with oil until
the powder is thoroughly wetted; Then water is
added all at once and the mixture is vigorously
and continuously triturated until the primary
emulsion formed is creamy white.
 Additional water or aqueous solutions may be
incorporated after the primary emulsion is
formed.
 Solid substances ( e.g. active ingredients,
preservatives , color, flavors) are generally
dissolved and added as a solution to the primary 27

28. WET GUM METHOD (ENGLISH
METHOD)
 By this method the same proportion of oil, water and gum
are used as in the dry gum method, but the order of mixing
is different and proportion of ingredients may be varied
during the preparation of the primary emulsion. The gum is
triturated with water to form a mucilage; Then oil is slowly
added in portions , while triturating .After all the oil is added
, the mixture is triturated for several minutes to form the
primary emulsion. Then other ingredients are added as in
continental method.
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29. BOTTLE METHOD OR FORBES
BOTTLE METHOD
 Used to prepare emulsions of volatile oils, or
oleaginous substances of vary low viscosities.
 Powdered acacia ( or other gum) is placed in a dry
bottle and two parts of oil are added, Then the
bottle is capped and thoroughly shaken.
 A volume of water approximately equal to that of
the oil is added in portions and the mixture
thoroughly shaken after each addition. When all
of the water is added , the primary emulsion thus
formed may be diluted to the proper volume with
water or an aqueous solution of other formulative
agents
 This method is not suitable for viscous oil as they
are not thoroughly agitated in bottle when mix
with emulsifying agentsss.
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30. PREPARATION OF
EMULSIONS ON LARGE
SCALE
1-Group the ingredients on the basis of solubility in
aqueous and oil phases.
2-Determine the type of emulsion required and calculate
an appropriate HLB value.
3-Blend two emulsifiers to achieve desired HLB.
4-Dissolve the oil soluble ingredients and emulsifier into
oil phase and heat at 70 – 80 degree C.
5-Dissolve the water soluble ingredients in water and
heat at same temperature as that of oil phase.
6-Add aqueous phase to the oil phase with agitation.
Examine the emulsion for its stability.
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31. PROCESSING EQUIPMENT FOR
EMULSIONS
Agitators
Mechanical Mixers
Colloid Mill
Homogenizers
Ultrasonic Devices
Microfluidic Devices
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32. AGITATORS
These are frequently used for emulsion formation
Preferred for low viscosity oils
Lab Shaker mixers
Shaking tends to break globules of dispersed phase
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33. MECHANICAL STIRRER
An emulsion may be stirred by means of various impellers
mounted on shaft which are placed directly into the system
to be emulsified. If viscosity of emulsion is low then simple
top entering propellers are used in lab and for production.
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34. MECHANICAL STIRRER
If more viscous agitation is required or if preparation has
moderate viscosity , turbine type mixers are employed
both in lab and on production.
Other mixers, provided with paddle-blades, counter-
rotating blades, planetary action blades are available for
special requirements.
Degree of agitation is controlled by the speed of impeller
rotation , but pattern of liquid flow and efficiency of
mixing are controlled by
Types of impeller
Its position in the container
The presence of baffles
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35. HOMOGENIZERS
In a homogenizer the dispersion of two liquids achieved
by forcing their mixture ,through a small inlet orifice, at
high pressure.
A homogenizer generally consist of a …..
1) pump, which raises the pressure of dispersion
between 500-5000p
2) an orifice , through which the fluid impinge upon the
homogenizing valve held in place of the valve seat by a
strong spring. This valve set at the 90 degree to the flow
of liquid.
As the pressure builds up, the spring is compressed and
some of dispersion escape between the valve seat, at this
point the energy that has been stored in liquid as a
pressure , is released and subjects the product to
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36. HOMOGENIZER
36

37. HOMOGENIZER
Homogenizer is based on the principle that when large
globules of a coarse emulsion is passed under the
pressure through a narrow irifice are broken into small
globules of high g=degree of uniformity and stability
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38. ULTRASONIC DEVICES
The preparation of emulsions using ultrasonic vibrations.
100 – 500 kHz oscillations through high frequency
oscillator.
Not suitable method for large scale production.
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39. COLLOID MILL
The emulsion is passed through stator and high speed
rotor revolving at 2000 – 18000 rpm.
Gap adjustment is 0.001 inches and above.
Usually used for size reduction of solids in suspensions
and emulsions.
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40. MICROFLUIDIC DEVICES
Used to produce very fine particles.
The process subjects the emulsion to an extremely high
velocity through micro channel into interaction chamber.
These particles are subjected to shear, turbulence,
impact and cavitation.
Advantages of this technique are lack of contamination
in the final product and easy scale up.
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41. MICROFLUIDIC DEVICES
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42. EMULSION STABILITY (
INSTABILITY) - TYPES
Physical instability
i. Flocculation
Ii. Creaming or sedimentation
iii. Aggregation or coalescence
Iv. Phase inversion
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43. PHYSICAL INSTABILITY OF
EMULSIONS
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Emulsion
Coalescence
Flocculation
Emulsion
Breaking

44. PHYSICAL STABILITY OF
EMULSION
Creaming :
Creaming is the upward movement of
dispersed droplets of emulsion relative
to the continuous phase ( due to the
density difference between two
phases).
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45. PHYSICAL STABILITY OF
EMULSION
 Aggregation, Coalescence, Breaking
 Aggregation : Dispersed particles come
together but do not fuse.
 Coalescence is the process by which
emulsified particles merge with each to
form large particles.
 Breaking is the destroying of the film
surrounding the particles.
 The major factor to prevent coalescence is
the mechanical strength of the interfacial
film. 45

46. PHYSICAL STABILITY OF
EMULSION
Phase inversion
An emulsion is said to invert when it changes from an
o/w to w/o or vice versa.
Addition of electrolyte :
Changing the phase volume ratio :
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47. STRESS CONDITION
Stress conditions normally employed for evaluating the
stability of emulsions include
Aging and temperature
Its is stated that many emulsions are perfectly stable at
40-45°C temp but cannot tolerate 55 °C or above.
Following would be the problems including
Viscosity
Partitioning of emulsifiers
Inversion phase
Crystallization of certain lipids
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°C

48. STRESS CONDITION
The normal effect of aging in emulsion at elevated
temperature is accelerated coalescence or creaming.
Most emulsion become thinner at elevated temperature
and vice versa.
2) Centrifugation
The shelf life under normal storage condition can be
predicted by observing the separation of dispersed phase
due to creaming and coalescence when emulsion
exposed to centrifugation
Ultra centrifugation creates three layers
Top layer, intermediate and pure aq layer
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49. STRESS CONDITION
3) agitation
Emulsion droplets are in Brownian movement, in fact no
coalescence of droplets take place unless droplet
impinges upon each other. Some micro emulsion become
cloudy due to short agitation in blender. Similarly
conventional emulsion deteriorate due to gentle rocking
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50. STRESS CONDITION
Physical parameters
phase separation
Viscosity
Electrophoretic properties
-Zeta potential
-Electrical conductivity
Particle size number analysis
Chemical parameters
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51. ASSESSMENT OF AN
EMULSION
Shelf life
The final acceptance of an emulsion depends on the
stability. Apperance and functionality of the packaged
products
Container
Interaction of ingredient with container
Loss of water or volatile ingredients through container or
closure
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