Pharmaceutical Emulsions: Iqra Zulfiqar (R#33)
Pharmaceutical Emulsions: Iqra Zulfiqar (R#33)
Pharmaceutical Emulsions: Iqra Zulfiqar (R#33)
EMULSIONS
- A type of Disperse System
Iqra Zulfiqar
(R#33)
By:
Company
LOGO
Topics to be Covered
1
Stability of Emulsions
Manufacturing of Emulsions
Pharmaceutical Application
Introduction
Types of emulsions
Classification of Emulsions
Theories of emulsification
Additives for formulation of emulsion
Emulsion
Suspension
is a dispersion in
which the dispersed
phase is composed
of small globules of
a liquid distributed
throughout a vehicle
in which it is
immiscible
is a two phased
system in which a
finely divided solid is
dispersed in a
continuous phase of
solid, liquid, or gas.
Emulsions (Definition)
An emulsion is a
thermodynamically unstable
system consisting of at least two
immiscible liquid phases one of
which is dispersed as globules
in the other liquid phase
stabilized by a third substance
called emulsifying agent.
-OR-
An emulsion is a dispersion in
which the dispersed phase is
composed of small globules of
a liquid distributed throughout a
vehicle in which it is immiscible.
Classification of Emulsion
Based on:
Oil in Water
(O/W): Oil
droplets
dispersed in
water
Water in Oil
(W/O): Water
droplets
dispersed in oil
Dispersed
phase
size of
Liq. droplets
Based on:
0.2 50 mm
Macro emulsions
(Kinetically
Stable)
0.01 0.2 mm
Micro emulsions
(Thermodynamically
Stable)
Types of Emuslion
Simple
emulsions
(Macro
emulsions)
Oil-in-water (O/W)
Water-in-oil (W/O)
- diameter greater than
0.1 m
Multiple
emulsions
Oil-in-water-in-oil
(O/W/O)
Water-in-oil-inwater
(W/O/W)
Micro
emulsions
Nano emulsions
- thermodynamically
stable optically
transparent , mixtures of a
biphasic oil water system
stabilized with surfactants
Lotions
Vitamin
drops
Linime
-nts
Emulsions
Creams
Ointments
Theories of Emulsification
Surface
Tension
Theory
by lowering of
interfacial
tension
OrientedWedge
Theory
mono molecular
layers of
emulsifying
agents are
curved around a
droplet of the
internal phase
of the emulsion
Interfacial
Film theory
A film of
emulsifying
agent
prevents the
contact and
coalescing of
the dispersed
phase.
Antimicrobial
Preservative
Emulsifying
agent
Auxiliary
Emulsifiers
# Emulsifying Agents
They are the substances added to an emulsion to prevent the coalescence of
the globules of the dispersed phase. They are also known as emulgents or
emulsifiers.
They help in formation of emulsion by three mechanisms.
- Reduction in interfacial tension thermodynamic stabilization
- Formation of a rigid interfacial film mechanical barrier to coalescence
- Formation of an electrical double layer electrical barrier to approach
of particles.
Pharmaceutically acceptable emulsifiers must also :
Be stable .
Be compatible with other ingredients .
Be non toxic .
Possess little odor , taste , or color .
Not interfere with the stability
of efficacy of the active agent .
Classification of Emulsifiers
1
Synthetic
Surface active
agents
( Monomolecular
films)
2
Semi synthetic and
natural
Hydrophilic colloids (
Multi-molecular
films)
Classification of Surfactants
Cationic
Nonionic
Anionic
Soaps
-Mono valent
-Polyvalent
-Organic
Sulphates
Sulphonates (CH3(CH2)n CH2SO3 Na+)
Company Logo
Classification of Hydrocolloidals
Semisynthetic
Includes mainly cellulose derivatives like sodium
carboxymethyl cellulose, hydroxyl propyl cellulose and
methyl cellulose. They are used for formulating o/w
type of emulsions. They primarily act by increasing the
viscosity of the system. e.g., methyl cellulose,
hydroxypropyl cellulose and sodium carboxy methyl
cellulose.
Natural
-Plant origin
Polysaccharides
(Acacia, tragacanth, agar, pectin, lecithin)
-Animal origin
Proteins ( Gelatin)
Lecithin
Cholesterol
Wool fat
Egg yolk
Bentonite,( Al2O3.4SiO2.H2O),
Veegum ( Magnesium Aluminium silicate)
Magnesium trisilicate
Metallic hydroxides
Magnesium hydroxide
Aluminium hydroxide
# Auxiliary Emulsifiers
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.
# Antimicrobial Preservatives
The preservative must be :
Less toxic
Stable to heat and storage
Chemically compatible
Reasonable cost
Acceptable taste, odor and color.
Effective against fungus, yeast, bacteria.
Available in oil and aqueous phase at effective
level concentration.
Preservative should be in unionized state to
penetrate the bacteria.
Preservative must no bind to other components
of the emulsion
# Antioxidants
Autoxidation occurs by free radical reaction
Can be prevented by
absence of oxygen,
a free radical chain breaker
by reducing agent
# Examples:
Gallic acid, Propyl gallate - pharmaceuticals and cosmetics - Bitter taste
Ascorbic acid Suitable for oral use products
Sulphites - Suitable for oral use products
L-tocopherol - pharmaceuticals and
cosmetics -Suitable for oral preparations
e.g. those containing vitamin A
STABILITY OF EMULSION
Section contains:
Physical Instability
Creaming
Flocculation
Phase Inversion
I - Flocculation
The reversibility of
flocculation depends upon
strength of interaction between
particles as determined by:
a the chemical nature of
emulsifier,
b the phase volume ratio,
c. the concentration of dissolved substances, specially
electrolytes and ionic emulsifiers.
II - Creaming
Upward creaming, is due to the dispersed phase is less dense than the
continuous phase. This is normally observed in o/w emulsions. The velocity of
sedimentation becomes negative.
Downward creaming occurs if the dispersed phase is heavier than the continuous
phase. Due to gravitational pull, the globules settle down. This is normally
observed in w/o emulsions.
III- Coalescence
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.
This type of closed packing induces
greater cohesion which leads to coalescence.
In this process, the emulsifier film around the globules is
destroyed to a certain extent. This step can be recognized by
increased globule size and reduced number of globules.
Coalescence is observed due to:
Insufficient amount of the emulsifying agent.
Altered partitioning of the emulsifying agent.
Incompatibilities between emulsifying agents.
Breaking:
This involves the change of emulsion type from o/w to w/o or vice versa.
When we intend to prepare one type of emulsion say o/w, and if the final
emulsion turns out to be w/o, it can be termed as a sign of instability.
MANUFACTURING OF EMULSION
Section contains:
Extemporaneous Methods
Large Scale Methods
Extemporaneous Methods
Emulsification process can be carried out by four methods mainly:
Bottle Method
Auxiliary Method
Heat :
Emulsification by vaporization
Emulsification by phase inversion
Low energy emulsification
Mechanical equipment for emulsification (Agitation)
Equipements
Equipements
Agitators
Mechanical
stirrers
Propeller
mixers
Colloid
mills
Ultrasonifiers
Mechanical Stirrers
An emulsion may be stirred
by means of various impellers
mounted on shafts, which are
placed directly into the
system to be emulsified.
This is used for mixing,
suspending, milling,
dispersing, disintegrating
solids etc. & reduces batch
time. It consists of stator and
rotor assembly. The rotor
rotates inside the stator
assembly which is fixed with
three tie rods to the motor.
Propeller Mixers
Simple top entering propeller mixers are adequate
for routine development work in the laboratory and
production.
The degree of agitation is controlled by propeller
rotation but the pattern of liquid flow and resultant
efficiency of mixing are controlled by the type of
impeller, its position in the container, the presence
of baffles, and the general shape of the container.
These stirrers can not be used when :
vigorous agitation is needed,
extremely small droplets are needed.
Foaming at high shear rates must be avoided.
These mixers may have paddle blades, counter
rotating blades or planetary blades .
Major Types
Turbine Type Mixers
Homogenizers
Colloid Mills
They operate on principle of high shear
which is normally generated between
rotor and stator of the mill.
Colloid mill consists of a fixed stator
plate and a high speed rotating rotator
plea.
Material drawn or pumped through an
adjustable gap set between the rotor and
stator is homogenized by the physical
action and he centrifugal force is created
by high rotation of the rotor which
operates within 0.005 to0.010 inch of the
stator.
ROTOR AND
STATOR
Ultrasonifiers
Ultrasonic energy s used to produce
pharmaceutical emulsions.
These transduced piezoelectric
devices have limited output and are
expensive.
They are useful for laboratory
preparation of emulsions of
moderate viscosity and extremely
low particle size.
Commercial equipment is based n
principle of Pohlmn liquid whistle.
The dispersion is forced through an
orifice at modest pressure and is
allowed to impinge on a blade. The
pressure range is from 150-350 psi .
This pressure causes blade to
vibrate rapidly to produce an
ultrasonic note. When the system
reaches a steady state, a cavitational
field is generated at the leading edge
of the blade and the pressure
fluctuations of approx. 60 tones psi
can be achieved in commercial
equipment.
Dilution
Conductivity
Dye-solubility
Tests
Refractive index
measurement
Filter paper
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.
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.
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.
PHARMACEUTICAL APPLICATIONS
Emulsions can be used for following dosage forms:
Oil
Products
O/W
Parenteral
a. I/V route :
Lipid nutrients are emulsified and given to patients by i/v rout. Such
emulsions have particle size less than 100 nm.
b. Depot injections :
W/o emulsions are used to disperse water soluble antigenic
materials in mineral oil for i/m depot injection.
Topical
Products
washable character,
Acceptable viscosity,
Less greasiness.
REFERENCES