What is the relationship between

milk and emulsion?

PH 201.42 1
 Biphasic Liquid dosage forms
Should have two separate phases

Suspensions Emulsions
Solid in liquid Liquid in liquid
suspension dispersion
(Insoluble) (Immiscible)

PH 201.42 2
 EMULSIONS: What are they?
An emulsion is a thermodynamically stable two-
phase system consisting of at least two immiscible
liquids, one of which is dispersed in the form of small
droplets throughout the other with the help of an
emulsifying agent.

Size of droplets - range from around 0.1 to 10 µm in diameter -

Larger ones visible with light microscopy

• Microemulsion: Droplets size range 0.01 to 0.1 m m

• Macroemulsion: Droplets size range approximately 5 m m.

Internal phase or Dispersed phase or Discontinuous phase

External phase or Continuous phase
Continuous phase
Dispersed phase

PH 201.42 3
Emulsions tend to have a cloudy appearance –
Because the many phase interfaces (the boundary
between the phases is called the interface) scatter light
that passes through the emulsion.

Emulsions are unstable and thus do not form spontaneously–

Energy input through shaking, stirring, homogenizers, or
spray processes are needed to form an emulsion.

Over time, emulsions tend to revert to the stable state of oil

separated from water –
Emulsifying agents can increase the kinetic stability of
emulsions greatly so that, once formed, the emulsion
does not change significantly over years of storage.

PH 201.42 4
 Emulsions: Why are they used?
Systemic uses
Oral
• Nutrition - triglycerides (e.g. vegetable oils)
• Means of masking unpleasant flavour
Parenteral
• Nutrition - triglycerides
• Delivery of drugs poorly soluble in water
• Site-directed delivery of drugs
• Necessarily small droplet size,
• Comparable to chylomicrons
• Delayed-release (e.g. I.m.)

PH 201.42 5
Emulsions: Why are they used?

Local uses
Skin
• May be o/w or w/o
• Applied or rubbed
• Application of drugs
• Viscous and remain where applied
• Emolliency, greasiness, acceptability
• Called "creams", "lotions"
Oral/rectal
• Constipation
• Called "emulsions"/"enemas"

PH 201.42 6
Examples of emulsions as drug delivery systems

• Diazepam: Emulsion eliminates pain due to

crystallization of a solubilized drug following dilution in the
bloodstream

• Vegetable oils: Delivery of substrates high in metabolic

energy

• Propofol: Liquid anaesthetic dissolved in emulsified oil

• Fluorocarbons: Artificial blood substitutes

PH 201.42 7
 Advantages

1. Can mask the bitter taste and odor of drugs - make them more
palatable. e.g. castor oil, cod-liver oil etc.
2. Can be used to prolong the release of the drug - sustained
action.
3. Essential nutrients like carbohydrates, fats and vitamins can all
be emulsified and can be administered to bed ridden patients as
sterile intravenous emulsions.
4. Protects drugs against oxidation or hydrolysis.
5. Intravenous emulsions of contrast media have been developed
to assist in diagnosis.
6. Emulsions are used widely to formulate externally used products
like lotions, creams, liniments etc.

PH 201.42 8
 Disadvantages

1. Highly unstable
2. Susceptible to temperature and pH changes.
3. Microbial growth and subsequent spoilage is common
in emulsions prepared by using natural emulgents.
4. Size of globules is of great concern in parenteral
administration

PH 201.42 9
 Classification
Emulsions

Macro emulsions Mini emulsions Molecular emulsions

Primary emulsions / Secondary emulsions /
Simple emulsions Multiple emulsions

PIT emulsions
Micro emulsions
O/W/O Micellar emulsions
O/W
Nano emulsions
W/O/W

W/O

PH 201.42 10
 Droplet size and the appearance of emulsions
M
I
N
I

E
M
U
L
S
I
O
N
S

Macroemulsion Microemulsions

PH 201.42 11
Thermodynamic stability of different types of emulsions

PH 201.42 12
 ……Types of emulsions
Oil in Water emulsions (O/W)
• Oil is the dispersed phase and water is the dispersion
medium.
• Used mainly for internal/oral use
• Externally - non greasy creams, lotions and liniments.
• Cosmetic products as o/w emulsions can easily be removed
from the surface of the skin
• Example: Castor oil emulsion, foundation creams, vanishing
creams.

Water in oil Emulsions (W/O)

• Water is the dispersed phase and oil is the dispersion
medium
• Used mainly externally as lotions and creams.
• Also effective as cleansing cream. Example: Cold creams.
PH 201.42 13
Microscopic view of emulsions

PH 201.42 14
 Differences between O/W and W/O emulsions
Oil in water emulsion (O/w)
Water is the dispersion medium
Oil is the dispersed phase
Non greasy and easily removable from the
skin surface
Used externally to provide cooling effect e.g.
vanishing cream
Water soluble drugs are more quickly
released from o/w emulsions
Preferred for formulations meant for internal
use as bitter taste of oils can be masked.
Give a positive conductivity test as water is
the external phase which is a good
conductor of electricity.
Water in oil emulsion (w/o)
Oil is the dispersion medium
Water is the dispersed phase
Greasy and not water washable
Used externally to prevent evaporation of
moisture from the surface of skin e.g. Cold
cream
Oil soluble drugs are more quickly released from
w/o emulsions
Preferred for formulations meant for external use
like creams.
Do not give a positive conductivity test as oil is
the external phase which is a poor conductor of
electricity.
15
PH 201.42
 Multiple Emulsions
• Multiple emulsions are primarily used for formulating
sustained release dosage forms.

Types
• Oil in water in oil (o/w/o) emulsion
• Water in oil in water (w/o/w) emulsion

PH 201.42 16
 Identification tests for emulsions

Since emulsion (o/w or w/o) looks the same in appearance

with naked eyes, therefore certain tests have been
developed to differentiate between them.
They are
1. Dilution test (emulsion can be diluted only with external
phase)
2. Dye test (using water or oil soluble dyes)
3. Electrical conductivity test (o/w emulsions conduct
electric current)

PH 201.43 17
 Identification tests for emulsions……

4. Fluorescence test (some oils fluoresce under UV light)

5. Cobalt chloride paper test (CoCl2 blue paper turns pink
when hydrated)
6. Depending on the direction of creaming

At least two tests should be done to reach a conclusive

decision about the identity of the emulsion.

PH 201.43 18
 1. Dilution test
Few drops
of water Water distribute
uniformly O/W emulsion

Few drops Water separate

of emulsion out as layer W/O emulsion

Based on the solubility of external phase of emulsion.

- o/w emulsion can be diluted with water.
- w/o emulsion can be diluted with oil.

Dilution Test for oil in water Dilution test for water in oil emulsion
emulsion
PH 201.43 19
 2. Dye Solubility Test

• Emulsion is mixed with a water water soluble dye amaranth

soluble dye such as amaranth
and observed under the
microscope, if the continuous
phase appears red and
continuous phase colorless,
then it is w/o type.
• Similarly if an oil soluble dye
such as Scarlet red or Sudan
III is added to an emulsion and
the continuous phase appears
red, then it w/o emulsion.
PH 201.43 20
 3. Electrical Conductivity Test

• Based on the basic principle that water is a good

conductor of electricity.
• This test will be positive as water is the external phase.
• An assembly consisting of a pair of electrodes connected
to a lamp is dipped into an emulsion.
• If the emulsion is o/w type, the lamp glows.

PH 201.43 21
 ……..Electrical Conductivity Test

For oil in water emulsion For water in oil emulsion

PH 201.43 22
 Cobalt chloride
4. Cobalt Chloride Test paper (Dried)

When an emulsion is added to

a dried filter paper soaked in
cobalt chloride solution, it turns If oil is the If water is the
from blue to pink, indicating continuous continuous
phase phase
that the emulsion is o/w type.

Remains same Turns pink

PH 201.43 23
 5. Fluorescence Test

Emulsion

If an emulsion on exposure
to ultra-violet radiations
shows On exposure to UV light
continuous florescence under
microscope w/o
Spotty fluorescence o/w

W/O Emulsion O/W Emulsion

PH 201.43 24
 6. Depending on the direction of creaming

Most of the oils are lighter than water except clove oil.

Creaming is the formation of relatively concentrated

emulsion.

If creaming occurs at the top of the emulsion

- oil is the dispersed phase (O/W)

If creaming occurs at the bottom of the emulsion

- water is the dispersed phase (W/O)

PH 201.43 25
 What is Emulsification?

W/O
OIL

Emulsifier
WATER

O/W

PH 201. 44 26
Concept of formulation

PH 201. 44 27
Concept of formulation

PH 201. 44 28
 Formulation

1. Selection of oily phase

- Toxicity of the oil
- Desired consistency
- Possible chemical incompatibilities
For oral emulsions
- Mineral oils
- Edible vegetable oils

PH 201. 44 29
 Formulation…..

2. Phase volume ratio

The internal phase concentration will be determined by

A. Dosage requirement
For O/W emulsions – 31-45% water
For W/O emulsions - < 25% water
B. Consistency desired

PH 201. 44 30
 Formulation…..
3. Other additives in emulsion

A.Viscosity builders – To buildup the viscosity of the external

phase
Eg: Hydrocolloids

B. Antimicrobials – To protect against microbial degradation

Eg: Benzoic acid, Methyl paraben

C. Antioxidants – To protect against rancidity

Eg: BHT,BHA, Gallic acid,
Propylgallate, Tocopherols.

D. Organoleptic additives - To improve palatabilty of emulsion

Colour, Flavour and Sweetners.

PH 201. 44 31
 Formulation…..

4. Choice of emulgent

Selection based on
A. Toxicity
B. Chemical incompatibility
C. The cost
D. Types of emulsion desired
E. Shelf life

PH 201. 44 32
 HYDROCOLLOIDS
NATURAL INORGANICS SEMISYNTHETICS SYNTHETICS
Plants Animal Mineral Colloidal Methylcellulose Carbopol
Acacia Gelatin Bentonite alumina
Carboxy Polyox
Tragacanth Casein Attapulgite Milk of methylcellulose
magnesia Colloidal
Alginates Wool fat Veegum Hydroxy silicon
Magnesium methylcellulose dioxide
Chondron Egg yolk oxide
Microcrystalline
Guar gum Magnesium cellulose
Pectin trisilicate

PH 201. 44 33
 TYPES OF EMULGENTS
Hydrocolloids

Natural – Plant source (always forms o/w emulsions)

• Thickening, gelling and stabilizing agents.

• Water-soluble polysaccharides.
• Amount required is very low.
• Also interact with proteins, allowing for protein stabilization
and protection applications.

PH 201. 44 34
 Natural – Plant source
Gum acacia
• Solubility: Cold water soluble
• pH ~4.0 - 4.8
• Constituents:
• Anionic exudate polysaccharide of calcium salt of arabic acid,
along with magnesium and potassium.
• Major monosaccharides: D-galactose, D-glucuronic acid;
• Used as powder, 35% mucilage or as 10% syrup
• Low viscosity
• Milk reactivity
• Newtonian flow
• Excellent emulsifier
• Foam stabilizer
• Adhesive
• Film-foaming
PH 201. 44 35
 Natural – Plant source
Tragacanth
• Astralgus gummifer is a plant exudate from a shrub
originally located in the Middle East.
• Two components: water-swellable [bassorin]
water-soluble [tragacanthin]
• Others
• Acid stable and resistant
• Bifunctional emulsifier
• Creamy texture
• Pseudoplastic
• Film former
• Bodying agent
• Adhesive
• Suspending agent
• Thickener
• pH 5.0-6.0 PH 201. 44 36
 Natural – Plant source
Alginate

• Polysaccharide produced from brown seaweed.

• Brown seaweed contains mixed alginic acid salts, which
are the basic raw materials used in the production of
alginates.
• The seaweed grows mainly in the inter-tidal zones of
cold waters in many countries throughout the world.

PH 201. 44 37
 Natural – Plant source
Guar gum
• From the seeds of (Leguminosa: Cyamopsis tetragonolobus),
• The hull and germ of the seed are separated from the
endosperm by a natural milling process.
• Galactomannan consisting of a mannose chain branched
with galactose units.
• High water-binding capacity - extremely high viscosity in
water-based systems even at low dosage levels.
• Mainly used as a thickening agent.
• Stable at pH values between 3 and 11 - Used in a wide
range of products.
• cold soluble.
• synergism with xanthan gum. 38
PH 201. 44
 Natural – Plant source
Pectin

• The word “pectin” stems from the Greek word

“pektos”, which means firm and hard.

• Commercial pectin is derived from the peel of citrus

fruits (lemon, lime and orange) or from apple
pomace.

PH 201. 44 39
 Natural – Plant source
Agar
Polysaccharide found in the cell walls of some red algae
Composition:
• Sulfated galactose monomers
• D-galactose, 3,6-anhydro-L-
galactose
linear polymer of sulfated D-
glucuronic acid and
• Agarose (a neutral polymer of
agarobiose)
• Agarose-beta-D-gal;
• 3 anhydro-alpha-L-gal
• D-glcA=D-glucuronic acid
• D-galA=D-galacturonic acid
• L-gulA=L-guluronic acid
40
PH 201. 44
 Animal source
Egg yolk
Contains lecithin & Cholesterol
Produces o/w emulsions
Gelatin
Animal protein – o/w emulsion – requires preservative.
Incompatible with negatively charged hydrocolloids such as
acacia, tragacanth or agar.
Available in two forms
Pharmagel A (Acid treated) – Isoelectric point 7 - 9.
Pharmagel B – Alkali treated – Isoelectric point 4.7 - 5.
Wool fat
Contains cholesterol and its esters.
W/o emulsions – ointments & Creams.
PH 201. 44 41
 Mineral source

Bentonite
• Only official clay
• Colloidal aluminium silicate
• Non toxic , not absorbed from GIT
• Two types – Calcium bentonite & Sodium bentonite
• Bentonite magma (5%) give either o/w or w/o emulsions
depending on the order of mixing.

PH 201. 44 42
 Mineral source

Others
• Pulgite
• Veegum
• Colloidal alumina
• Magnesium oxide
• Magnesium trisilicate
• Milk of Magnesia

PH 201. 44 43
 Semi synthetic hydrocolloids

Methylcellulose
• Soluble in cold water
• Insoluble in hot water
• Non ionic
• Stable over wide range of PH
• Non toxic
Carboxy methylcellulose
• Available in low, medium and high viscosity grades
Hydroxy ethylcellulose
• Un affected by PH from 4 -10.
Microcrystalline cellulose
PH 201. 44 44
 Synthetic Hydrocolloids

Carbopol
• Carbopol 934, 940 & 941.
• More compatible
• Suitable for both internal & external preparations
Polyox
• Polymerized product of Ethylene oxide
• MW in millions
• Coagulated by electrolytes and temperature

PH 201. 44 45
 Surface active agents
• The term surfactant is a blend of "surface
acting agent".
• Surfactants are usually organic
compounds that are amphipathic,
meaning they contain both hydrophobic
groups (their "tails") and hydrophilic
groups (their "heads").
• They are soluble in both organic solvents
and water.
• Surfactants constitute the most important
group of detergent components.

PH 201. 45 46
 Uses of Surfactants
1. Emulsifiers
Water in Oil - Low HLB
Oil in Water - High HLB
2. Foam Stabilizers
3. Lipid Crystal Modifiers
4. Wetting Agents
5. Solubilizers
6. Starch Complexers
7. Protein Modifiers
8. Detergents
PH 201. 45 47
 Surfactants
Anionics Cationics Nonionic Ampholytics

Alkali soaps Esters

Quarternary
Metallic soaps ammonium Glyceryl
compounds monostearate Meranols
Amine soaps
Eg. Benzalkonium
Sulphated oils Sorbitan esters
chloride
Sulphated alcohols Ethers Deriphates

Aliphatic sulphonates Brij

Aromatic sulphonates Octoxynol

Tyloxynol

Ethers Esters

Tweens
Spans

PH 201. 45 48
A micelle - the lipophilic ends of the surfactant molecules dissolve in the
oil, while the hydrophilic charged ends remain outside, shielding the rest of
the hydrophobic micelle

PH 201. 45 49
 Critical micelle concentration (CMC)

• All surfactants possess the common property of lowering

surface tension when added to water in small amounts.

• The characteristic discontinuity in the plots of surface

tension against surfactant concentration can be
experimentally determined.

• The corresponding surfactant concentration at this

discontinuity corresponds to the critical micelle
concentration

PH 201. 45 50
 How do surfactants work?

Types of emulsion

PH 201. 45 51
 How do surfactants work?

+ + + + +
+ +
+ +
+ + + +
+ ++
OIL + +
+ + OIL
+ +
+ + + +
WATER +
+ + + + +
+ + +

SINGLE SURFACTANT MIXED SURFACTANT

• Cetrimide • Cetyl alcohol
• Repulsion • Cetrimide
Less stable film More stable condensed film (barrier)
Charge repulsion between drops

PH 201. 45 52
 Good emulgent?
Contact angles

> 90° produces o/w Equals 90° ? Depends on oil : water ratio
< 90° produces w/o

Poor emulgent
• Poorly soluble in both phases
• Concentrates at the interface
• Relative attraction for the two phases
PH 201. 45 53
 Anionics
• An anionic surface-active agent is the
reaction product of an organic compound such as a high
molecular weight acid or alcohol
with an inorganic compound such as sodium hydroxide
or sulfuric acid,
yielding a product wherein the organic part of the
molecule, or the water-insoluble part of the molecule,
has a negative charge and the water-soluble part of the
molecule wherein the sodium ion has a positive charge.
• The anionics have the advantage of being high and
stable foaming agents.
54
PH 201. 45
 Cationics

• Cationics are formed in reactions where

alkyl halides react with primary, secondary, or tertiary fatty

amines.

Here the water-insoluble part of the molecule has a

positive charge and the water-soluble part of the molecule
is negatively charged.
• Have no detergent action when formulated into an alkaline
solution.

PH 201. 45 55
 Nonionic
• Nonionic surface-active agents have a
hydrophobic/hydrophilic balance wherein there is neither
a negative nor a positive charge in either part of the
molecule, thus giving it the nonionic terminology.

• These surface-active agents have the advantage that

they are not affected by water hardness or pH changes
as the anionic and cationic surfactants are, and in many
cases it is an advantage that they are considered
medium to low foaming agents.
PH 201. 45 56
 Surfactants –
Affirmed GRAS Emulsifiers
• Diacetyl tartaric acid esters of mono- and diglycerides.
• Glyceryl monooleate.
• Glyceryl monostearate.
• Glyceryl behenate.
• Lecithin
• Mono- and diglycerides.
• Monosodium phosphate derivatives of mono- and
diglycerides

PH 201. 45 57
 Mono & diglycerides

• Most commonly used

• Generally as mono & di

• HLB values range from 1 to 10

• Produced by transesterification of glycerol and

triacylcerides

PH 201. 45 58
 Polysorbates

• Polyoxyenthyene esters of sorbitan monoesters

• Polysorbate 60
• Polyoxyethylene sorbitan monostearate or Tween 60
- HLB = 14.9
Polysorbate 65
• Polyoxyethylene sorbitan tristearate
• Polysorbate 80
• Polyoxyethylene sorbitan tristearate
• Special dietetic foods, fat soluble vitamins
PH 201. 45 59
 Sorbitan monostearate

• Sorbitan monostearate approved for food use

• HLB = 4.7

• Used in conjunction with polysorbates

PH 201. 45 60
 Lecithin

• A mixture of phospholipids including phosphatidyl

cholines, phosphatidyl ethanolamines, inositol

phosphatides, etc

• Can be chemically modified by provide a wide range of

HLB values for various applications

PH 201. 45 61
 Hydrophillic - Lipophillic Balance (HLB)

• This is a concept for choosing emulsifiers.

• The value of HLB ranges from 1-20.

• Low HLB emulsifiers are soluble in oil while high HLB

emulsifiers are soluble in water..

PH 201. 45 62
 HLB….

The HLB of a surfactant is a measure of the degree to

which it is hydrophilic or lipophilic, determined by

calculating values for the different regions of the

molecule, as described by Griffin.

Other methods - by Davies.

PH 201. 45 63
 Griffin's method

Griffin's method for non-ionic surfactants as described in

1954 works as follows:

HLB = 20 * Mh / M

Where Mh is the molecular mass of the hydrophilic

portion of the Molecule, and

M is the molecular mass of the whole molecule, giving a

result on an arbitrary scale of 0 to 20.

PH 201. 45 64
 How to calculate HLB value?

For alkanoic (fatty) acid esters of polyhydric alkanols

HLB = (1-S/A)
where S is the saponification number and
A is the acid number of the fatty acid

For non-ionic surfactants with polyoxyethylene as the only

hydrophilic component
HLB = E/5
where E is the percentage w/w of PEG (polyoxyethylene)
PH 201. 45 65
 Griffin's method…

The HLB value can be used to predict the

surfactant properties of a molecule:

1 to 3.5 Antifoaming agents

3.5 to 6 W/O emulsifiers
7 to 9 Wetting and spreading agents
8 to 12 O/W emulsifiers
12 to 15 Detergents
15 to 20 Solubulizers or Hydrotropes.

PH 201. 45 66
 Solubility and HLB

Solubility HLB Range

No dispersability in water 1-4

Poor Dispersion in water 3-6

Milky appearance 6-8

Stable milky appearance 8 - 10

Translucent to clear dispersion 10 - 13

Clear solution 13 +

PH 201. 45 67
Surfactant HLB

Sorbitan trioleate (Span 85) 1.8

Sorbitan tristearate (Span 65) 2.1
Sorbitan sesquioleate (Arlacel 83) 3.7
Glyceryl monostearate, NF 3.8
Sorbitan monooleate, NF, (Span 80) 4.3
Sorbitan monostearate, NF, (Span 60) 4.7
Sorbitan monopalmitate, NF, (Span 40) 6.7
Sorbitan monolaurate, NF, (Span 20) 8.6

PH 201. 45 68
Polyoxyethylene sorbitan tristearate, (Tween 65) 10.5
Polyoxyethylene sorbitan trioleate, (Tween 85) 11.0
Polyethylene glycol 400 monostearate 11.6
Polysorbate 60, NF, (Tween 60) 14.9
Polyoxyethylene monostearate (Myrj 49) 15.0
Polysorbate 80, NF, (Tween 80) 15.0
Polysorbate 40, NF, (Tween 40) 15.6
Polysorbate 20, NF, (Tween 20) 16.7

PH 201. 45 69
Ingredient "Required HLB" for
w/o o/w Emulsion

Acid, Stearic 6 15
Alcohol, Cetyl -- 15
Alcohol, Stearyl -- 14
Lanolin, Anhydrous 8 10
Oil, Cottonseed 5 10
Oil, Mineral 5 12
Petrolatum 5 12
Beeswax 4 12
PH 201. 45 70
 Emulsification

Comminution (Destruction)

Mechanical energy or pressure is doing the job the most

widely used procedure

Condensation (Construction)

Thermodynamics takes care swelling of colloidal

systems such as micelles or solid (polymer) particles
with liquids

PH - 201 - 46 71
• Methods for preparing Emulsions for Internal
use
The methods commonly used to prepare emulsions can be
divided into two categories:

• Trituration Methods
• Dry Gum Method
• Wet Gum Method

• Bottle Method
PH - 201 - 46 72
Comminution methods

PH - 201 - 46 73
 Comminution - Structure of the Emulsion
Which liquid forms the dispersed phase and which will be
the continuous one?

Influenced by
• Volume ratio

• Kind of the emulsifying agent

• Concentration

Shear exceeds the cohesive forces of the liquids in the

drops they split up to smaller units
Cleavage occurs as long as a balance between the
external stress and the internal stress is reached
PH - 201 - 46 74
Emulsion preparation by Comminution is influenced by:

• Comminution power
• Duration of the comminution
• Viscosity of both phases
• Interfacial tension
• Degradation after comminution is stopped

PH - 201 - 46 75
 Acacia emulsions
• Emulsions for internal use at dispensing table.
• Primary emulsion is to be prepared first.
• Primary emulsion is the initial thick emulsion during which
globules of internal phase is reduced to the minimum size.
• The quantities of oil, water and gum for primary emulsion
depends on the type of oil used.
• The primary emulsion can be diluted with any volume of
water.
• Two methods – Dry gum method
Wet gum method can be used for the
preparation of primary emulsion

PH - 201 - 46 76
Table 46.1 : Parts of Oil : Water : Gum, for primary emulsion

Type of oil Example Quantities for primary emulsion

Oil water Gum

Fixed Almond oil 4 2 1
Arachis oil
Castor oil
Cod liver oil

Mineral Liquid paraffin 3 2 1

Volatile Turpentine oil 2 2 1

Cinnamon oil
Peppermint oil

Oleo-resin Male fern extract 1 2 1

PH - 201 - 46 77
 Continental or Dry Gum Method

Also called as "4:2:1" Method

4 parts (volumes) of oil
2 parts of water
1 part of gum used in the preparation of primary emulsion

Acacia or other o/w emulsifier is triturated with oil in a

perfectly dry Wedgwood or porcelain mortar until
thoroughly mixed.

PH - 201 - 46 78
After the oil and gum have been mixed, the two parts

of water are then added all at once and the mixture is

triturated vigorously.

The finer the globules, the whiter is the product.

PH - 201 - 46 79
 Dry gum method….

• Do not use glass mortar: Too smooth a surface to produce

the proper size reduction of the internal phase.

• Always use dry measures to measure oil

• Pestle and mortar must be absolutely dried

• Quantities of oil, water and gum should be

measured/weighed accurately

PH - 201 - 46 80
• Trituration must be vigorous, continuous and

unidirectional after the addition of water until the

primary emulsion is formed (hearing of clicking sound).

• Dilute primary emulsion with more water in small additions

PH - 201 - 46 81
Emulsions prepared by dry gum method…
R
Olive oil 30 mL
Purified water upto 120 mL
Formula for primary emulsion
Olive oil 30 mL
Water 15 mL
Gum acacia 7.5 g
Method:
• Measure the oil in a dry measure.
• Powder gum acacia in a dry mortar. Add oil and mix
thoroughly.
• Water is added all at once and Triturate unidirectionally,
vigorously and continuous until clicking sound is heard.
(Formation of primary emulsion)
PH - 201 - 46 82
• Add more quantity of water until it become pourable.
• Remove any foreign particles if present.
• Transfer to the tared final container.
• Add rinsing too.
• Incorporate more water to produce the final volume.
• Shake well.
• Cork, label and dispense.

PH - 201 - 46 83
 English or Wet Gum Method
• Is not popular because the results are not good.
• Same proportion of oil, water and gum are used as in the
continental or dry gum method but the order of mixing is
different.
• Mucilage of the gum is prepared by triturating acacia (or
other emulsifier) with water.
• The oil is then added slowly in portions, and the mixture
is triturated to emulsify the oil.
PH - 201 - 46 84
 Special cases

1. Inorganic salts:

Dissolved in part of vehicle and diluted before adding to

the diluted emulsion in small amounts with constant

stirring.

High concentrations of electrolytes may precipitate the

emulsifying agent.

PH - 201 - 46 85
2. Tinctures and other Alcoholic solutions:
The emulsion is diluted to its final volume less the volume
of the alcoholic solution.

The latter is added drop by drop to the centre of the

emulsion with constant stirring.

PH - 201 - 46 86
 Special cases….

3. Substances insoluble in oil or water:

Such substances are finely powdered and gradually

triturated with diluted emulsion, or they can be mixed

with acacia powder before preparing emulsion.

PH - 201 - 46 87
4. Modification when preparation of oil is small:
In case of acacia emulsion, if oil phase is less than 20%,

istarts creaming readily. Thus to prevent this a bland

fixed oil (e.g. Arachis oil) should be added to increase the

oil phase upto 20% of the total volume e.g. emulsion of

calciferol and Bromoform.

PH - 201 - 46 88
 Official preparations

Castor oil Emulsion

Castor oil 30ml
Mucilage of Acacia 60ml
Chloroform water to 180ml
Comments:
It is a o/w type of emulsion prepared by emulsification with
mucilage of acacia (40% acacia in chloroform water). It
is internally taken for its purgative action.
Method:
Use the wet-gum method for acacia emulsion.
PH - 201 - 46 89
 Bottle or Forbes Bottle Method

• Useful for extemporaneous preparation of emulsion from

volatile oils or oleaginous substance of low viscosity.

• Put powdered acacia in a dry bottle

• Add 2 parts of oil

• Thoroughly shake the mixture in the capped bottle.

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• A volume of water approximately equal to the oil is then

added in portions, the mixture being thoroughly shaken after

each addition.

• This method is not suitable for viscous oils (i.e. high

viscosity oil).

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 Emulsions for External use

Soap emulsions
e.g. soft soap is used as an emulsifying agent. If the
quantity of soap is not mentioned in the preparation,
the following proportions:

For fixed and Volatile oils : 10 percent of the weight of oil.

For Fats : 20 percent of the weight of oil

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 Emulsions for External use
Method :
• Finely powder any solid ingredients and mix it with
soap in a mortar.
• Add oil in small amount, mix well after each addition.
• Transfer the above mixture in a beaker.
• Take a calibrated bottle about 50% larger than the final
volume of product, in which water is added.
• Add the oily mixture from the beaker into bottle is small
quantites, shaking vigorously after each addition
• Add any other fluid liquid and makeup the volume. If
necessary, pass it through a muslin strainer
• Finally, transfer gently to a container of the correct size
PH - 201 - 46 93
 Official preparation
Turpentine Liniment B.P.
Soft soap 75g
Camphor 50g
Turpentine oil 650ml
Purified water 225ml

Comments:
It is an emulsion-type liniment made with an alkali soap. It
is used as counter-irritant.

Method:
Follow the general method of preparation of soap
emulsions.
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 Ammonium soap type

Ammonium soap is prepared by interaction of a fatty acid

and ammonia during the preparation.

White Liniment B.P.C.

Ammonium Chloride 12.5g

Dilute ammonia solution 45.0ml
Oleic Acid 83.3ml
Turpentine oil 250.0ml
Purified water 625.0ml
PH - 201 - 46 95
Method:
• Mix the turpentine oil and oleic acid in a bottle 50%
larger than the prescribed volume.
• Add an equal volume of warm water (approx. 50°C) to
the dilute ammonia solution and add this diluted
ammonia solution, in small amounts, to the oily liquid,
shaking vigorously after each addition.

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• Dissolve the ammonium chloride in the rest of the water and

add to the bottle, in small amounts, again shake vigorously

after each addition.

• Transfer to calibrated bottle and finally make-up the volume

PH - 201 - 46 97
 ‘Lime’ Cream type

Lime creams are w/o type of emulsions.

E.g. Olive oil contains sufficient free fatty acids which can
combine with lime water producing enough calcium
soap to emulsify rest of the oil.

Calamine 1g
Zinc Oxide 1g
Olive oil 15ml
Lime water 15ml

PH - 201 - 46 98
Method:

Sift suitable quantities of the powders. Weigh out the

required amount and mix in a mortar. Use a
separate sieve for each powder.

Use olive oil to produce a smooth paste, add the lime

water (freshly prepared) and triturate briskly to
produce a good emulsion.

PH - 201 - 46 99
 Instabilities in Emulsions
• An emulsion is a thermodynamically unstable preparation. So
care has to be taken that the chemical as well as the physical
stability throughout the shelf life.

• There should be no appreciable change in

• Mean particle size or

• Size distribution of the droplets of the dispersed phase and

• Secondly droplets of the dispersed phase should remain

uniformly distributed throughout the system.

PH - 201 - 47 100
Instabilities seen in emulsion can be
grouped as

PH - 201 - 47 101
Instabilities seen in emulsion can be
grouped as

PH - 201 - 47 102
 Instabilities of emulsions

Stable Creaming/ Aggregation Coalescence Cracking

emulsion Sedimentation

Degree of severity

PH - 201 - 47 103
 1) Creaming or Sedimentation

• An emulsion is said to cream when the oil or fat rises up

to the surface (Creaming) or settles at the bottom
(Sedimentation), but remains in the form of globules,
which may be redistributed throughout the dispersion
medium by shaking.

• An oil of low viscosity tends to cream more readily than

one of high viscosity.

PH - 201 - 47 104
• Increasing the viscosity of the medium decreases the
tendency to cream.

• It is a reversible phenomenon which can be corrected

by mild shaking.

PH - 201 - 47 105
 Stokes' Law
The factors affecting creaming are best described
by stroke’s law
V= 2r2 (d1-d2) g/9η
Where
V = rate of creaming
r =radius of globules
d1 = density of dispersed phase
d2 = density of dispersion medium
g = gravitational constant
η = viscosity of the dispersion medium

PH - 201 - 47 106
 Stokes' Law

Creaming or sedimentation is

Directly proportional to:

1. Diameter of the particle squared
2. Difference in density between the particle and the
continuous phase
and
Inversely proportional to
3. Viscosity of the continuous phase

PH - 201 - 47 107
 Approaches to decrease creaming

Reduction of globule size:

Bigger is the size of the globules, more will be the

creaming.

Gglobule size should be reduced by homogenization.

PH - 201 - 47 108
Increasing the viscosity of the continuous phase:

More the viscosity of the continuous phase, less will the problem of creaming.

The viscosity of the continuous phase should be increased by adding suitable

viscosity enhancers like gum acacia, tragacanth etc.

PH - 201 - 47 109
 2) Aggregation and Coalescence or Cracking

• The aggregation and possible coalescence of the

dispersed droplets to reform separate bulk phases.
• These are more serious problems than creaming.

• In aggregation

• the dispersed droplets come together but do not fuse.

• It is not as serious as coalescence.
• It is somewhat reversible and upon shaking may form
emulsion.
• It is related to electrical potential on the droplet

PH - 201 - 47 110
• In coalescence
• The complete fusion of droplets and ultimate
separation of the two immiscible phases.

• It depends on the structural properties of the

interfacial film (Emulgent).

• Leads to breaking of emulsion and will not restore

upon shaking.

PH - 201 - 47 111
 Reasons for cracking

• Insufficiency of emulgent
• Decomposition of emulgent
• Addition of substance incompatible with emulgent.
• Alteration of PH of the continuous phase.
• Presence of electrolyte
• Presence of antagonistic emulgent
Eg. Addition of Calcium oleate to an O/W Emulsion
prepared by using Sodium oleate
• Abrupt changes in temperature
• Microbial growth
• Addition of common solvent like alcohol
Eg. Turpentine Oil, Soft soap, Water

PH - 201 - 47 112
• Presence of antagonistic emulgent
Eg. Addition of Calcium oleate to an O/W Emulsion
prepared by using Sodium oleate
• Abrupt changes in temperature
• Microbial growth
• Addition of common solvent like alcohol
Eg. Turpentine Oil, Soft soap, Water

113
PH - 201 - 47
Salt (NaCl) Effect on the Emulsion Stability (2 day test)

Amount of Sodium chloride solution

20 ml 5 ml 2 ml 1 ml 0.5 ml 0.25 ml

PH - 201 - 47 114
 Effect of Temperature

At room temperature in Oven (130oF)

PH - 201 - 47 115
 3) Phase Inversion

• In phase inversion o/w type emulsion changes into

w/o type and vice versa.

• It is a physical instability.

• It may be brought about

• by the addition of an electrolyte or

• by changing the phase volume ratio or
• by temperature changes.

PH - 201 - 47 116
• Phase inversion can be minimized

• by using the proper emulsifying agent in adequate concentration,

• keeping the concentration of dispersed phase between

30 to 60 % and

• by storing the emulsion in a cool place.

PH - 201 - 47 117
 Packaging of Emulsions

• Depending on the use, emulsions should be packed in

suitable containers.
• Emulsions meant for oral use are usually packed in well
filled bottles having an air tight closure.
• Light sensitive products are packed in amber coloured
bottles.
• For viscous emulsions, wide mouth bottles should be
used.

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 Labelling of Emulsions

• The label on the emulsion should mention that these

products have to be shaken thoroughly before use.

• External use products should clearly mention on their

label that they are meant for external use only.

PH - 201 - 47 119
 Storage of Emulsions

• Emulsions should be stored in a cool place

• Refrigeration should be avoided as this low temperature

can adversely effect the stability of preparation.

PH - 201 - 47 120
 Preservation from microorganisms

Microorganisms can proliferate easily in emulsified

systems
• with high water content,
• particularly if carbohydrates, proteins or steroidal
materials are also present.

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•Contamination due to microorganisms can result
in problems

• such as color and odor change,

• gas production,
• hydrolysis,
• pH change and
• eventually breaking of emulsion.

Emulsified systems be adequately preserved.

PH - 201 - 47 122
 An ideal preservative should be

• Nonirritant
• Nonsensitizing
• Nontoxic in the concentration used
• Physically as well as chemically compatible with other
ingredients of the emulsions and with the proposed
container of the product
• Stable and effective over a wide range of pH and
temperature

PH - 201 - 47 123
• Have a wide spectrum of activity against a range of
bacteria, yeasts and moulds.

• Have high water solubility and a low oil/water partition coefficient

• Bactericidal rather than bacteriostatic activity

• It should not impart any taste, color or odor to the

product

PH - 201 - 47 124
 Examples of antimicrobial preservatives
• Parahydroxybenzoate esters
• Methyl, Propyl and Butyl parabens

• Organic acids
• Ascorbic acid and Benzoic acid

• Organic mercurials
• Phenylmercuric acetate and phenylmercuric nitrate

• Quarternary ammonium compounds

• Cetrimide

• Cresol derivatives
• Chlorocresol

• Miscellaneous agents
• Sodium benzoate, chloroform and phenoxyethanol.

PH - 201 - 47 125
 Preservation from oxidation

• Oxidative changes such as rancidity and spoilage due to

atmospheric oxygen and effects of enzymes produced by

micro-organisms is seen in many emulsions containing

vegetables and mineral oils and animal fats.

• Antioxidants can be used to prevent the changes occurring

due to atmospheric oxygen.

PH - 201 - 47 126
The ideal antioxidant should be

• Nontoxic
• Nonirritant
• Effective at low concentration under the expected
conditions of storage and use
• Soluble in the medium
• Stable
• For oral preparations - also be odorless and tasteless.

PH - 201 - 47 127
Commonly used antioxidants

• Alkyl gallate such as ethyl, propyl or dodecyl gallate

• Butylated hydroxyanisole (BHA)

• Butylated hydroxytoluene (BHT)

PH - 201 - 47 128