This document summarizes information about pharmaceutical emulsions and creams. It discusses the types of emulsions like o/w and w/o, the oils, emulsifying agents, and factors that determine emulsion type. It also covers emulsion instability mechanisms like flocculation, creaming, coalescence, and phase inversion. The roles of surface-active agents, hydrophilic polymers, and particles in emulsion stabilization are described. Characteristics of nanoemulsions and acceptable preparations are also summarized.
1. Pharmaceutical Disperse
Systems
Emulsions and Creams
Emulsion and creams refer to disperse systems in
which an insoluble is dispersed as droplets within a
liquid phase.
Creams are pseudoplastic systems with more
consistency than emulsions.
Creams and emulsions may be o/w or w/o
o/w/o, w/o/w can be prepared.
Generally o/w emulsions may be administered
topically and orally while w/o creams are for topical
applications.
2.
3. Oils
Liquid paraffin alone or with paraffin wax.
Unsaturated veg oils undergo autooxidation.
Liquid paraffin, turpentine oil, benzyl benzoate,
silicon, for topical use.
Castor oil, liquid paraffin orally.
Soya bean, safflower, fractionated cocanut oil, refined
fish oil and olive oil for parenteral use because rich in
linolinic acid.
4. Emulsifying agents
Provides electrostatic repulsive forces and steric
repulsive forces to counteract Vander Waal attractive
forces.
It increases the viscosity of the extended phase.
Thus,
Hydrophilic surfactant forms o/w emulsion and
lipophilic surfactants emulsify with low HLB
promoting w/o systems.
7. Characteristics of acceptable
preparation
Physical stability, no phase separation.
The flow properties ; should be easily removed from
the container, if intended for topical use it should be
easily spread over the affected area.
Formulation must be aesthetically and texturally
pleasing.
8. Advantages of pharmaceutical emulsions
Incorporation of drugs with low aqueous solubility.
May be used to mask the taste of therapeutic agents, the
external phase may be formulated to contain sweetening and
flavouring agents.
May be used to administer oils.
Irritancy may be reduced by formulating the drug within the
internal phase of o/w emulsion.
May be employed to patients having difficulty to swallow.
Employed for total parenteral nutrition.
More faster absorption.
Self-Emulsifying-Drug-Delivery System SEDDS.
10. Emulsions instability and theories of
emulsification – Role of surface-active agents
The oil phase is in droplets, spherical in shape as this is
minimum surface area.
If droplet contact another droplet will provide a big droplet of
surface area less than that of the two droplets prior to
coalescence. This process will continue till complete phase
separation. Then there are two layers of the two phases.
An interfacial tension exists at the interface between the two
layers due to imbalance between the two layers.
Thermodynamically this situation may be described in terms
of the change in the interfacial Gibbs free energy ∆G,
interfacial tension between the two phases ᵧo/w and the change
in the surface area of the disperse phase when this is dispersed
∆A.
∆G= ᵧo/w ∆A
11. Dispersion of one phase into the other will cause increase in the
interfacial surface area = increase in the Gibbs free energy =
instability.
Correction of this instability lead to coalescence.
Stabilization of the dispersion system is by emulsifying agents
which tend to reduce the interfacial tension and hence negate to
some extend the destabilizing effect of the increased surface area.
Sodium cetyl sulphate and cholesterol when used, form a stable
film due to their interaction at the interphase. The mechanical
properties of this adsorbed interfacial film is sufficient to prevent
disruption even when the shape of the droplets is changed.
The close-packed nature of the surface-active agent at the
interface resulted in a greater lowering of the interfacial tension.
Oleyl alcohol ( cis isomer of cholestraol ) result in a poor
emulsion but the trans isomer of oleyl alcohol, elaidyl alcohol
produce stable emulsion.
Adsorbed layer may carry electrical charges leading to repulsion
between adjacent droplets especially when using ionic surface-
active agents.
12. Emulsions instability and theories of
emulsification – Role of hydrophilic polymers
Hydrophilic polymers is used as emulsions stabilizer.
It has no effect in the interfacial tension.
They have the ability to adsorb at the interface between the
dispersed phase and the external phase to produce
multilayers that are highly viscoelastic (gel-like) and can
therefore withstand applied stresses without deformation
and hence preventing coalescence ( gel network theory).
Ionic polymers ( gelatin, sodium alginate, sodium
carboxymethylcellulose) then the multimolecular adsorbed
film will be charged and therefore will exhibit zeta potential.
Due to the presence of the adsorbed polymeric layer , stearic
stabilization of the droplets occurs.
Hydrophilic polymer will increase the viscosity of the
external phase of o/w emulsion and so will affect the
sedimentation rate of the droplets.
13. Emulsions instability and theories of emulsification –
Role of adsorbed particles
Addition of finely divided solid particles will
stabilize the emulsion.
If the particles is wetted by the aqueous
phase more than the oil phase it will produce
o/w emulsion ( aluminium hydroxide,
magnesium hydroxide, bentonite, kaolin)
If the particles wetted by the oil phase more
than the aqueous phase it will produce w/o
emulsion ( talc, carbon black)
14. Microstructure of creams
Oil in water composes of four layers:
1- dispersed oil phase stabilized by monomolecular film.
2- α- crystalline gel phase composed of bilalayers of surfactant
and alcohol separated by layers of interlamellar fixed water.
3- α- crystalline hydrates that shows limited swelling in water.
4- bulk continuous phase.
16. Types of emulsions
The type of emulsion depend on
several factors:
1. The volume of the internal phase.
2. The chemical properties of the
film surrounding the internal
phase.
3. The viscosity of the internal and
external phases.
17. The volume of the internal phase
The critical value of the internal phase is 74% for o/w
emulsions but in practice phase volume ratio is 50%.
The higher the phase volume of the internal phase ,
the greater the probability of droplet coalescence.
The critical value for w/o emulsion is 40%
18. The chemical properties of the film surrounding the
internal phase.
The chemical composition of the surface-active agent and
hydrophilic polymer at the external phase ( droplet)
dictate the whether w/o or o/w is formed.
Oil droplets are stabilized by an adsorbed film composed
non-ionic and specially ionic surfactants or hydrated
hydrophilic polymer chain.
The surface-active agents and polymers are therefore
predominantly aqueous but also processing hydrophobic
groups.
Conversely in w/o emulsions, the droplets are stabilized by
the non-polar portion of the surface-active agent, which
protrudes into the non-aqueous external phase and so
enhancing the mechanical integrity and reducing the
tendency for internal phase to coalesce.
19. Surface-active agents and polymers that are predominantly
hydrophilic will form o/w and those are predominantly
hydrophobic will form w/o emulsion.
Surface active agents contain both hydrophilic and lipophilic
groups, therefore the contribution of these groups determine
whether the agent is hydrophilic or hydrophobic.
This ratio of contribution is termed as hydrophile-lipophile
balance HLB .
The HLB from 1 – 40, the water solubility of the surface-active
agent increases as the HLB increases.
Surface active agent exhibiting HLB 3-6 are used to produce
w/o emulsion.
- Sorbitan sesquioleate ( Arlcel 83) : HLB 3.7
- Sorbitan monooleate ( Span 80) : HLB 4.3
- Sorbitan monostearate ( Span 60) : HLB 4.7
- Glyceryl monostearate HLB 4.7
20. Surface-active agents that exhibit an HLB 6 – 9, form
non-stable milky dispersions in water
- Sorbitan monopalmitate ( span40) HLB 6.7 and
Sorbitan monlaurate (Span20) HLB 8.6.
Surface-active agents exhibiting HLB 9-16 are used to
produce o/w emulsions these agents form stable milky
dispersions ( HLB 9 – 10.5) and translucent clear
dispersion in water (HLB 10.5 -13) and clear solution
when HLB is 13 – 16).
- Polyoxyethylene sorbitan tristearate, monostearate
(Tween 65, 60) HLB 10.5
- Polyoxyethylene sorbitan monooleate (Tween 80) HLB
15
- Polyoxyethylene sorbitan monolaurate (Tween 20)HLB
16.7
The HLB value of ionic surfactant is greater than 16.
21. Bancroft rule: the phase in which the emulsifying
agent more soluble being the continuous phase.
Griffin HLB: HLB = (E+P)/5
E: percentage by weight of the oxyethylene chain
P: percentage by weight of polyhydric alcohol
groups.
23. HLB Phase Inversion Temperature
PIT
The temperature at which the nonionic surfactant gets a
hydrophobic tendency just exceeding its hydrophilic
tendency. The emulsion phases will invert consequently.
24. Types of surfactants “ Emulgents”
1- Naturally occurring surfactants
2- Synthetic and Semisynthetic
30. Viscosity of internal and external phases
As the viscosity is high, the diffusion of the surface-
active agent into the droplet will be reduced.
The viscosity is inversely proportional to the diffusion
coeffiecient of the surface-active agent.
The increased viscosity will affect the process of
coalescence of the droplet of the external phase.
If the viscosity of one phase is increased there is a
greater chance for this phase to be the external phase
of the emulsion.
31. Tests to identify the type of emulsion
Electrical conductivity, o/w can conduct
electrical current while w/o can not.
Dilution with water; o/w can be diluted
with water while w/o cannot be diluted.
Use of dyes; oil-soluble dyes will stain the
internal phase if the emulsion is o/w
where water-soluble dyes will dye the
internal phase of w/o emulsion.
33. Cracking – irreversible instability
Complete phase separation.
Reasons:
- Incorrect selection of emulsifying agent
- Presence of incompatible excipients. ( addition of cationic
surfactant as cetrimide to emulsion stabilized by anionic
surfactant as sodium oleate).
- Temperature heating above 70 or freezing will destroy the
emulsion. .
- Microbial spoilage.
- Prevention: addition of monolayer of hydrophilic and
lipophilic emulgent.
34. Flocculation
In the flocculated state the secondary
interactions( van der waals forces) maintain the
droplets at a definite distance of separation.
Application of shearing stress will redisperse
these droplets to form homogeneous formulation.
There is a possibility that the close location of the
droplets at the secondary minimum would enable
droplet coalescence to occur if the mechanical
properties of the interfacial film are compromised.
Prevented by presence of high energy barrier on
the droplets
35. Creaming
Either sedimentation or elevation of the droplets of the
internal phase producing a layer of concentrated emulsion
either at the top or at the bottom of the container but not
coalesces.
Upon shaking a homogeneous emulsion will result.
The rate of creaming may be described by Stocks' equation
and can be reduced by: where,
v is the velocity of creaming, a is the radius, η is the viscosity of the dispersion
medium, ρσ id the densities of the disperse medium and the dispersed phase.
- Particle size reduction by colloidal mill.
- Increase viscosity by addition of hydrophilic polymer to the
external phase of o/w emulsion or non-aqueous viscosity
enhancer ( aluminium stearate salts Thixin)into w/o
emulsions.
- Prevention is controlled by Stocks' Law.
ν=
𝟐𝒂𝟐𝒈(σ−ρ)
𝟗η
36. Phase inversion
Occurs whenever the critical value of the phase
volume ratio has been exceeded.
In o/w the ratio is 74:26
In w/o the ratio is 40:60
Addition of a substance that alter the HLB; Mg salt
to emulsion stabilized by Na Oleate.
Addition of electrolyte to emulsion stabilized by
anionic or cationic surfactant due the effect of the
common ion.
Heating emulsion stabilized by nonionic surfactant.
37.
38. Problem Reason Description Prevention
Creaming Large droplets separation of droplets under
the influence of gravity to form
a layer of more concentration (
cream)
1. Gentle shaking
2. Use smaller droplets.
3. Addition of viscosity modif
ier.
4. Increase the density of oil.
Flocculation It is in the
secondary
minimum
Association of droplets
separated by the continuous
phase. ( cluster of drops)
1. Mild agitation.
2. Use of suitable emulsifier.
Coalescence Droplets overcome
the repulsive
energy (primary
minimum)
Mergence of droplets to form
large droplet and continue till
cracking.
Emulsifiers mixture of
polymers.
Ostwald
ripening
Slightly soluble
dispersed phase.
Irreversible, the smaller
droplets dissolves and diffuse
through the continuous phase
and redeposit on larger
droplets.
1. Addition of small quantitie
s of immiscible second oil.
2. Addition of Pluronic
F68 surfactant.
3. Increase of viscosity.
39. Factors affecting the consistency of
emulsion
Volume concentration of the dispersed phase.
Particle size of the dispersed phase.
Viscosity of the continuous phase.
Viscosity of the dispersed phase.
Nature and concentration of the emulgent.
40. Formulation of
pharmaceutical emulsions
Type of emulsion?
Volume of internal phase?
Droplet size?
Viscosity of the internal and
external phases?
Selection of type and concentration
of emulsifying agents?
41. Type of emulsion?
Emulsion for oral and intravenous administration is
o/w.
For topical application ( creams) may be o/w or w/o
Most moisturizing formulations are w/o emulsions.
42. Volume of internal phase?
Volume of the internal phase according to
the type of emulsion should be within the
applied ratio.
43. Droplet size?
The rate of creaming may be reduced by droplet size
reduction.
Colloidal mill.
44. Viscosity of the internal and external
phases?
The difference between oral or parenteral
emulsion and cream is the increased viscosity of
creams.
Viscosity also affects the stability , controlling
the rate of upward/downward sedimentation.
45. Selection of type and concentration of
emulsifying agents?
Anionic surfactants are restricted to external
formulations.
To determine the type of emulsifying agent refer to the
HLB requirements of the internal phase of the
formulation.
If HLB is not known, a series of emulsions using a
mixture of surface-active agents is to be prepared.
Practically a mixture of different surface-active agents
is used and calculated on the basis of HLB.
The concentration of surface-active agent should be
the lowest possible to ensure stability.
47. Vehicles
Purified water and sterile water for injection.
Non-aqueous phase:
- Vegetable oils
- Petrolatum and mineral oils.
- Isopropyl myristate.
- Antioxidant; lipophilic as butalylated hydroxyl anisole
0.02 – 0.5% w/w.
- Favours and sweetening agents.
- Viscosity modifier, hydrophilic polymer.
- calculation of preservative in emulsion ( practical)
48. Preservative
P. hydroxybenzoate, benzoic acid, phenoxyethanol.
Incompatibility of Phenolic compounds and the
emulsifier polyoxyethelene nonionic surfactant:
- Destroy the preservative effect.
- destroy the emulsification properties.
49. Manufacture of emulsions
1. Dissolution of the oil-soluble components in the oil vehicle.
2. Dissolution of the water-soluble components in the aqueous
vehicle.
3. Mixing the two phase under turbulent mixing conditions.
Manufacture of creams involves mixing of the two heated
phases using a mortar and pestle and in industry using
homogenizer or ultrasonifier.