Emulsions
Alfred Martin
Lecturer: Dr. Majid R. Feddah
Introduction

Emulsion consists of two immiscible liquids one
of which is uniformly dispersed throughout the
other as droplets of diameter greater than 0.1µm.

To prepare a stable emulsion a third phase, an
emulsifying agent, is required.

Emulsions is a useful way to present oils and fats
in a palatable form.

Emulsions for external use are known as a lotion.
2
Oil in Water or Water in Oil
Oil
Water
Water in Oil
Oil in Water
3
Emulsion Types

Oil in Water, (O/W) the oil phase distributed as
globules in the aqueous phase (continuous phase).

Water in oil, (W/O) the water is distributed
through out the oil phase (continuous phase).

Pharmaceutical emulsion usually O/W emulsion.
4
Determining the type of emulsion
1. Water soluble dye to be dusted on the surface of
the emulsion:


O/W the dye will be dissolve the color & diffuse
through the system.
W/O, the dye will stay on as clumps on the tope
of the emulsion.
2. Dilution of the emulsion with water, if the
emulsion mixed freely with water, thus it is O/W.
5
Types of emulsion continue…
3. Electrical current test:
Electrodes connected to the external electric
source and immersed in the emulsion, if the
external phase is water a current will pass through
the emulsion.
4. Staining tests

Filter paper soaked in cobalt chloride solution
and allowed to dry
The filter paper will turns from blue to pink on
exposure to stable O/W emulsion.
6
Pharmaceutical Applications
1. Convenient of orally water insoluble liquids,
when the dispersed phase has unpleasant taste.
2. Increase the absorption (some ingredients such
as vitamins are absorbed completely when
emulsified with emulsifying agent).
3. For patients how can’t getting medicine and
nutrition's orally. (I.V Emulsion)
4. In many cosmetics preparations (dermatological
products, lotions and creams) because the
ability for spreading is high over the skin.
7
5. In diagnostic agents in x-ray examination.
6. In aerosols preparation for producing foams.
7. To prepare stable and homogeneous mixtures of
two immiscible liquids.
8. It permits the administration of a liquid drug in
a form of globules.
9. Reduce the droplet size of the oil, make it more
readily absorbed.
10. If the active ingredients irritating the skin, are
less irritant when used as internal phase.
8
Methods of Emulsion Preparation

1.
2.
Emulsion may be prepared in different methods
depends on:
The nature of emulsion component.
Available emulsion equipments.
In small scale a mortar and pestle, a mechanical
blender, a homogenizer.
In large scale, large tanks, and high speed mixer
homogenizer may be used to prepare an emulsion
9
In small scale
1. Continental or dry gum method.
2. English or wet gum method.
3. Bottle method.
10
Continental Dry Gum Method
The method is also referred to as the 4-2-1
(Oil-Water-Gum).
In this method:
1. The acacia or O/W emulsifier is triturated with the oil
in a dry wedgewood or porcelain mortar, until mixed.
A rough surface should be used, for good grinding to
reduce the globules size.
2. Then the two parts of water are added all at once.
3. The mixture triturated immediately, rapidly and
continuously until the primary emulsion is formed.
creamy white and produces a crackling sound.

11
Continental method continued.
4. Other liquid ingredients that are soluble in the
external phase may then be added.
5. Solid substances such as preservatives,
stabilizers colorants, and any flavoring material
usually dissolved in a water then added to an
emulsion.
6. Any substances that may interfere with the
stability of emulsion may added at the end.
12
English or Wet Gum method
1.
2.
3.
4.
5.
The same proportion of water, gum and oil is
used.
Triturating of acacia with water in a mortar.
The oil then is added slowly in portions.
The mixture is triturated to emulsify the oil.
The mixture is thoroughly mixed for several
minutes to insure uniformity of the emulsion.
Other substances may be added.
13
Bottle Method
1.
2.
3.
4.
5.
It is used for volatile oils or oleaginous
substances of low viscosity.
The powder acacia is placed in a dry bottle.
Two parts of oil then added.
The bottle is then shaken in a caped container.
A water is then added in portions.
When a primary emulsion is formed the other
ingredients is added.
It is not suitable for viscous oils.
14
Auxiliary Methods



To increase the quality of emulsion prepared by
any of the pervious methods:
The emulsion is passed through a hand
homogenizer.
The emulsion is forced to pass through a very
small orifice which reduces the globules of the
internal phase to a bout 5 µm.
15
In situ Soap method
The two types of soaps are developed by this method:
1. Calcium soap.
2. Soft soap
Calcium Soap: It is W/O emulsion contain vegetable
oils (Oleic acid in combination with lime water (calcium
hydroxide solution, USP).
• Prepared by mixing equal volumes of oil and the lime
water.
• The emulsifying agent is the calcium salt of the free fatty
acid which is formed from the combination of the two
entities.
 This formula is ideal where occlusion and skin softening
are desired.

16
Ideal Emulsion
Ideal Emulsion
1.
2.
3.
4.
5.
6.
Colorless
Odorless.
Tasteless.
Non-toxic.
Non irritant.
Able to produce stable emulsions at low
concentration.
18
Theories of Emulsification



1
No universal theory of emulsification.
Because emulsion can be prepared using several
different types of emulsifying agent, each of which
depends for its action on a different principles to
achieve a stable products.
Any theory to be acceptable should explain the
followings:
1. The stability of the product.
2. The type of emulsion formed.
19
2
What happened when two immiscible liquids are
agitated together?
Failure the two liquids to remain mixed, because :
The cohesive force between the molecules of
each separate liquid is greater than the adhesive
force between the two liquids.
The increase in the surface energy makes the
system thermodynamically unstable,
Hence the droplets have a tendency to coalesce.
3
To prevent coalescence:

Introduce third material (Emulsifying agent),
which form a film around the dispersed
globules and prevent them from come to each
other and form big one (globules).
Types of emulsifying agents
21
Types of Emulsifying Agents
4
1. Surface active agents:
Adsorbed at oil/water interfaces to form
monomolecular films - reduce interfacial tension.
2. Hydrophilic Colloids:
Form multi-molecular film around the dispersed
droplets of oil in water (O/W) emulsion.
3. Finely divided solid particles:
Adsorbed at the interface between two immiscible
liquid phases and form a film of particles around
the dispersed globules.
22
Summary


All of them form a film around the globules,
either mono, or multi layer, or particulate.
Table 18-1 page 488.
Classification of Dispersed Systems
Class
Range of particle
size
Characteristics of
the system
Examples
Molecular Dispersion
Less than 1.0nm (mµ)
Invisible in SEM, pass
through ultra filters
Oxygen molecules,
ordinary ions,
Glucose
Colloidal Dispersion
1.0nm to 0.5µm
Could be detected
under SEM
Colloidal silver
solution
Coarse Dispersion
Greater than 0.5µm (µ)
Visible under
microscope, not pass
through normal filter
Ref. Martin chapter 15, colloids
24
5
1.
Surfactant:
Monomolecular Adsorption:
Surface active agents, reduce the interfacial tension
because of their absorption at the oil water interface to
form monomolecular layer films.
 . The film should be:
1. Flexible, to reform rapidly in case of broken or disturbed.
2. The presence of surface charge, cause repulsion and
enhance stability of the emulsion.
3. Combination of more then one emulsifier are used in the
preparation of emulsion.
25
Recommendations

Atlas of surfactants, recommends that:
The hydrophilic Tween be combined with a lipophilic
Span, varying the proportion so as to produce the
desired O/W or W/O emulsion.

Tween 40 (polyoxyethylene sorbitan monopalmitate)
and Span 80 for stabilization of emulsion.

Mix of different emulsifying agents produce stable
emulsion such as , (sodium stearate, cholesterol,
sodium lauryl sulfate, glyceryl monostearate, tragacanth
and span).
7



The type of emulsion produced, depends on the
properties of emulsifying agent used.
This characteristics is called Hydrophile-Lipophyl
balance and referred to as (HLB).
It is the polar, and non-polar nature of the emulsifier.
Example: Sodium stearate C17H35COONa
─ The non-polar hydrophobic C17H35
go to oil.
is the lipophilic
─Polar group hydrophilic ─ COONa go to water.
The balance between the lipophilic and the hydrophilic
will determine the type of emulsion formed
27
HLB

The exam of the med
HLB
9
Whether a surfactant is an
 Emulsifier.
 Wetting agent.
 Detergent.
 Solubilizing agent.
It will be predicted from a knowledge of (HLB).
Each emulsifying agent is assigned an HLB value.
30
HLB continued


10
The usual range of HLB is between 1 to 20.
Material that are highly polar or hydrophilic have
higher number of HLB than materials less polar
lipophilic low number of HLB.
Materials having an:
HLB value (3-6) are lipophilic & produce W/O.
HLB value (9-12) are hydrophilic and produce O/W.
31
Rule of Bancroft
11

The type of emulsion is a function of the relative
solubility of the surfactant, the phase in which it is
more soluble being the continuous phase.

Emulsifying agent with a high HLB is soluble in water
and results in the formation of an (O/W) emulsion.
The reverse situation is true with surfactant of low
HLB, which tend to form (water in oil) emulsions.

12
HLB Values of emulsifying agents
Emulsifying agent
HLB value
Acacia
8.0
Sorbitan monolaurate
8.6
Sorbitan monostearate
4.7
Polysorbate 20
16.7
Polysorbate 60
14.9
Polysorbate 80
15.0
Sodium lauryl sulphate
40.0
Sodium oleate
18.0
Tragacanth
13.2
Triethanolamine oleate
12
33
13
II. Multi-molecular Adsorption & film
formation
Its hydrated lipophilic colloids, they considered
as surface active agents because they appear at
the oil water interface.
They differed from the surfactants in:
1. They do not cause an sufficient lowering of the
interfacial tension.
2. They form multi-layer rather a monolayer film at
the interface.

34
14



The action as emulsifying agents is due to the
multilayer formation around the droplets, so,
strong film which resist coalescence.
Another effect promoting stability is the
significant increase in the viscosity of the
dispersion medium.
These emulsifying agents are hydrophilic, and
they tend to promote the formation of O/W
emulsions.
35
III. Solid Particle Adsorption


15
Those solids particles are wetted by both oil and
water, so they can act as emulsifying agents.
They presents water and oil interface, where they
produce a film around the dispersed droplets.
By this way it prevent coalescence.
Powders which are wetted mainly by:
• Water form O/W emulsion.
• Oil they form W/O emulsion.

36
Physical Stability of Emulsions
16
Finished product and stability:
1. Absence of coalescence of the internal phase.
2. Absence of the creaming.
3. Maintenance of elegance with respect to appearance,
Odor, Color, and other physical properties.
4. Agglomeration of the internal phase and separation
from the product.
37
17
Physical stability continued

Creaming, resulting from flocculation and
concentration of the globules of the internal phase.
Is not considered as a mark of instability.

Creaming results from flocculation, which,
represent potential steps toward complete
coalescence of the internal phase.

In pharmaceutical dosage forms creaming is results
in lack of uniformity of drug distribution.
38
Phase Inversion
18

It is the change of emulsion type from W/O to
O/W or vice versa.
It is considered as emulsion instability.

An oil in water emulsion stabilized with sodium
stearate can be inverted to the water in oil by
adding calcium chloride to form calcium
stearate.
Inversion occur by alteration in phase volume
ratio.

39
Classification of the emulsion instability
1.
2.
3.
4.
Flocculation and creaming.
Coalescence and breaking.
Miscellaneous physical and chemical changes.
Phase inversion.
Instability of Emulsion
19
41
Creaming and Stokes Law

20
If the dispersed phase is less dense than the
continuous phase (the case in O/W) emulsion, the
velocity of sedimentation become negative, that
results in upward creaming.

If the dispersed phase is heavier than the
contiguous phase (the case in W/O) emulsion, the
globules will settle in the bottom of the container
(creaming in the downward direction).
42
Factors reducing creaming in emulsion


21
Viscosity:
Increasing the viscosity of the external phase, by
adding thickening agents such as Methylcellulose,
Tragacanth, or Sodium alginate.
Globules size:
Reduction in the globules size by homogenization
to reach below 2 to 5 µm.
43
Coalescence and Breaking

22
Creaming is a reversible process.
It can re-dispersed by mixing and homogenization,
as the oil globules are still surrounded by the
protective film of the emulsifying agent.

Breaking is irreversible.
In this case the film surrounded the globules are
destroyed and the oil tend to coalesces
44
Coalescence and Breaking



23
Reduction in the globules size does not necessarily
lead to increased the stability of the emulsion.
Optimum degree of dispersion for each particular
system exists for maximum stability.
Viscosity alone does not produce stable emulsion,
however viscous emulsion are more stable than
mobile ones.
The phase volume ratio, the volume of oil and the
volume of water in the emulsion, the best is 50
parts of water:50 parts of oil.
45
24

Cracking:
Is the coalescence of dispersed globules (internal
phase) and separation of the disperse phase as a
separate layer.
(It is irreversible process and re-dispersion cannot
be achieved by shaking).
46
Electrolytes




25
Emulsion can be stabilized by electrostatic repulsion
between the droplets, by increasing their zeta
potential.
Lecithin is used to stabilize emulsion.
Lecithin produces very stable emulsion of triglyceride
acids in water for intravenous administration.
The stability of these emulsion some times is poor
because in clinical practice they are mixed with
electrolytes, amino acids, and other compounds for
parenteral nutrition.

The addition of positively charged species such as
sodium and calcium ions or cationic amino acids,
reduces the zeta potential and may cause
flocculation.

Heparin, an anticoagulant, is a negatively charged
polyelectrolyte that causes rapid flocculation in
emulsions containing calcium and lecithin.
Emulsifier

The most important factors in stabilization of
an emulsion is the physical properties of
emulsifier film at the interface.
To be effective, an emulsifier film must be:
1.
2.
3.
4.
Tough (strong).
Elastic
Should form rapidly during emulsification.
Form a film around the globules and protect the
globules from re aggregation during manufacturing
the film, then slowly increases the film strength over
a period of days or weeks.
26
Evaluation of Stability
1.
27
Size frequency analysis form time to time as the product ages.
Microscopic observation of separated internal phase.
The particle diameters are measured, and a size frequency
distribution of particles ranging from 0-0.9, 1-1.9 etc.
2.
Accelerating the separation process, which normally takes place
under stress conditions.
i. These methods employ freezing, thaw-freezing cycles, and
centrifugation.
ii. Electrical conductivity changes, during short heating cooling
heating cycles.

The stability index indicates the relative change in conductivity
between two cycles.
The smaller the conductivity, the greater is the stability of the
emulsion.
29
Source of contamination in emulsions


Contamination may be introduced from a
variety of sources including:
Natural emulsifying agents, for example,
starch, acacia gum etc, .
1.
2.
3.
4.
5.
Water, if not properly stored.
Carelessly cleaned equipment.
Poor closures on containers.
Environment where the emulsion prepared.
Container and closures systems.
51




Preservation of Emulsion
30
Is it necessary to achieve sterile condition in an
emulsion?
What about emulsion for parenteral use?
Different components of emulsion:
Water, Oil, emulsifying agents, color, odor, and
microbial contaminations.
Bacteria degrade nonionic & anionic emulsifying
agents, (glycerin, and vegetable gums) which,
presents as thickeners in the formula, resulting
consequence deterioration of the emulsion
52
Preservation of Emulsion - 2



31
The main problem is to get adequate concentration
of preservative in the system.
Factors should be considered to achieve this:
Emulsion is an heterogeneous system, hence
partitioning of the preservative is occurs between
water and oil phase.
Bacteria grow at the aqueous phase, and the
preservative partitioned to the oil phase, hence the
concentration of the preservative in aqueous phase
in not enough to prevent bacterial growth.
53
Preservation of Emulsion - 3



32
The phase volume ratio is significant in this regards.
The preservative must be in an un-ionized state to
penetrate the bacteria membrane.
The preservative must not be bound to other
ingredients in the emulsion since the complex form
(preservative-X) are ineffective as preservatives.
54
Preservatives used in Emulsions-4
Benzoic acid: (0.1% ) at pH below 5.
2. Esters of parahydroxybenzoic acid
such as methyl paraben (0.01 – 0.3%).
1.
33
3. Chloroform Water (0.25% V/V).
4. Chlorocresol (0.05 - 0.2%).
5. Phenoxyethanol (0.5 - 1.0%).
6. Quaternary ammonium compounds (cetramide).
7. Organic mercurial compounds such as
phenylmercuric nitrate and acetate (0.002 -0.01%).
55
Rheologic properties of Emulsion
The flow properties of emulsion is important
according to the type of use:
1. In dermatological preparations:

Spreadability is essential.
2. In case parenteral preparations:
Flow of emulsion through needles is important.
3.
The removal of emulsion from bottle and
tubes
56
4. The behavior of an emulsion in the various
operations employed in the large-scale
preparations.
5. Most emulsion exhibit Non-Newtonian flow.
57
Emulsifying agents

These agents helps in the production of stable
dispersion by reducing interfacial tension and
then maintaining the separation of the droplets
by forming a barrier at the oil water interface.

Effective emulsifying agents are surface-active
agents, these have hydrophilic groups which are
oriented towards the water, and lipophilic nonpolar toward the oil. extra
58
Oil
Water
Extra
59
Extra
60
W/O/W
Oil in water
Extra
61
Emulsifying agents



Emulsion type determine by the solubility of the
emulsifying agent, if the emulsifying agent is more
soluble in water, i.e. hydrophilic then water will by
the continuous phase and O/W emulsion will
formed,
If the emulsifying agent is more soluble in oil, i.e.
hydrophobic then oil will by the continuous phase
and W/O emulsion will formed,
If some material is added which alters the solubility
of the emulsifying agent, this balance may be altered
and the emulsion may change type.
62
Naturally Occurring Emulsifying Agents
These agents come from animal or vegetable sources.,
the quality is vary and are susceptible to microbial
contamination.
1.
Polysaccharides:
- Acacia the best emulsifying agent 4 extemporaneously
prepared oral emulsions (it form a thick film at the
oil-water interface) to prevent the coalescence.
- Tragacanth is used to increase the viscosity of an
emulsion and prevent creaming.
- Other polysaccharides, such as Starch, Pectin and
Carrageenan, are used to stabilize an emulsion.
Extra
63
Semi-Synthetic polysaccharides

Low viscosity grades of:
Methylcellulose and Carboxymethylcellulose will be
form oil in water emulsion (O/W).
Sterol-containing substances:
These agents act as water in oil (W/O)
emulsifying agents.
(Beeswax, wool fat and wool alcohols).
Extra
64
Surfactants
Those agents contain hydrophilic and lipophilic
regions in the molecule.
 Classification according to their ionic
characteristics:
1. Anionic. 2. Cationic, 3. Non-ionic 4. Ampholytic.
Anionic Surfactants: Its organic salts which in
water have surface active anion.
They must be in ionized form to be effective.
Emulsion made with ionic surfactant are stable at
alkaline pH.

Extra
65
Example
1. Sodium Stearate. (o/w)
2. Calcium oleate (w/o).
3. Triethanolamine (TEA) oleate (o/w).
4. Sodium lauryl sulphate. (o/w)

66
Cationic Surfactant





These are quaternary ammonium compounds,
which, have surface active cation.
They are used in the preparation of O/W
emulsion for external used and must be in
ionized form to be effective.
Emulsion formed by cationic surfactant are
stable at acidic pH.
The cationic surfactant have antimicrobial
activity.
Example: Cetrimide and Benzalkonium chloride
67
Non-Ionic Surfactant

Non-ionic these are synthetic materials and
make up the largest groups of surfactants.

They are used to produce either (O/W) or
(W/O) emulsion for both external and internal
use.

Type of emulsion formed is depends on the
balance of hydrophilic and lipophilic groups
which is given by Hypophil Liphophyl Balance
68
Factors affecting the flow properties
1. Viscosity related properties of dispersed phase.



The phase volume ratio.
particle size distribution.
The viscosity of the internal phase.
 When volume concentration of the dispersed phase is
low, the system is Newtonian, as the volume
concentration increased, the system become more
resistant to flow and exhibits pseudo plastic flow, and
at very high concentration plastic flow occur.
When the volume conc. Approaches 0.74, inversion
may occur.
69
By increasing the concentration of the
dispersed phase
Newtonian
Plastic

Pseudo plastic
phase inversion.
Reduction in the particle size increases the
viscosity, the wider the distribution, the lower
the viscosity when compared to system having a
similar mean particle size but narrower
distribution.
70
2. The emulsifying agent.



The type of emulsifying agent used will affect
the particle flocculation and interparticle
attraction and this will affect flow.
The greater the concentration of the emulsifying
agent the higher will be the viscosity of the
product.
The physical properties of the film and its
electric properties are also significant.
71
Antioxidant

Some oils are liable to degradation by oxidation
and therefore antioxidant may be added to the
formulation.

Antioxidants used in oral emulsions which are
odorless and tasteless include ascorbic acid,
citric acid, sodium metabisulphite and
sodium sulphite.
72
Evaluation of Stability
73
Preservation of emulsion
74
Microemulsions



Clear, transparent solution, but unlike micellar
solubilized systems, microemulsions may not be
thermodynamically stable.
Its between stable solubilized solutions and
ordinary emulsions, which are relatively
unstable.
Microemulsion contain droplets of oil in a water
phase or droplets of water in oil with diameters
of about 10 to 200 nm, and the volume fraction
of the dispersed phase varies from 0.2 to 0.8
75




A third phase is used for emulsification of the
system such as surfactant and co-surfactant .
The micro-emulsion is studied as drug delivery
system for the following reasons:
To increase bioavailability of the drug poorly
soluble in water by incorporation of the drug
into the internal phase.
Micro-emulsion have also been considered as
topical drug delivery systems.
76
Micro-emulsion continued



Hydrophilic surfactants may be used to produce
transparent o/w emulsion of many oils
including flavor oils and vitamin oils such as A,
D and E.
Surfactant in the HLB range of 15 to 18 have
been used in preparation of such emulsions.
Surfactants commonly used in the preparation
of such oral liquid formulations are:
Polysorbate 60
Polysorbate 80
77
Advantages of microemulsion
1. Rapid and efficient oral absorption of drug
compared to solid dosage form.
2. Enhance trans-dermal drug delivery through
increased drug diffusion into the skin.
3. Potential application of microemulsion in the
development of artificial red blood cells and in
the targeting of cytotoxic drugs to cancer cells.
78
Stability of emulsions
In general the emulsions considered as
unstable systems.
1. The internal phase tends to form aggregates of
globules.
2. Large globules or aggregates rise to the top or
fall to the bottom of the emulsion, to form a
concentrated layer of internal phase called
“Creaming”.
3. Emulsions may affected by microbial
contaminations, and growth and by other
chemical and physical changes.
79

Creaming is a reversible process.
According to stokes’ equation, the rate of separation
of the dispersed phase of an emulsion is related to:
dx d 2 (ρ i  ρ e )g

dt
18η
1.
2.
3.
The particles size of the dispersed phase.
The differences in the density between the phases.
The viscosity of the external phases.
80
Rate of separation increased by:
1. Increasing particle size.
2. Increasing the differences in density between
the internal and the external phase dispersed.
3. Decreased by increasing the viscosity of the
vehicle.
81
Another destruction occur in the emulsions is the
coalescence of the globules of the internal phase
and the separation of that phase into a layer.
• This called “breaking” of the emulsion, and the
emulsion described as being cracked or broken.
• Care should be taken to protect emulsion from
the external environment conditions cold and
heat, freezing and thawing.
• Emulsions are transported to different countries
with different climate conditions so stability
should cover these variations.
82
Stability of emulsions




If the emulsion is light sensitive, a special
container, may be used.
For emulsions susceptible to oxidative
decomposition, antioxidants may be included in
the formulation.
Methylparaben and propylparaben are frequently
employed to serve this function.
Alcohol in the amount of 12-15% based on the
external phase volume is frequently added to
orally used o/w emulsions fro preservation.
83
Examples of oral emulsions
1. Mineral oil emulsion:
Mineral oil
Acacia
Syrup
Vanillin
Alcohol
Purified water (qs)
Prepared by dry gum method.
2. Simethicone Emulsion
3. Caster oil emulsion
500ml
125g
100ml
40mg
60ml
1000ml
84
Gels and Magmas
Semi-rigid systems in which the movement of the
dispersing medium is restricted by an interlacing threedimensional network in the system.
 A high degree of physical or chemical cross-linking
may be involved.
 Some gels are clear in appearance other are turbid. The
ingredients used may not be molecularly dispersed
(soluble or not soluble).
Two types of gels:
1. Single phase gels (the macromolecules are
distributed throughout the liquid in such a way no
boundaries exist between them and the liquid.
2. Two phase system or magma or milk The gel mass
consists of floccules of small distinct particles

85
Colloidal dispersions




“Sol” is a term to describe a dispersion of solid
in either a liquid, a solid or a gaseous dispersion
medium.
A prefix such as hydro- for water.
Alco- for alcohol.
Aerosol to describe a dispersion of a solid or a
liquid in a gaseous phase.
86
Colloidal dispersion there is no exact point of the
particle size to be considered as a colloidal
dispersion.
 In general solids in a range between (1nm to
0.5μm) called colloidal dispersion.
 Colloidal particles > than atoms, ions or molecules.
The difference between the true solution and the
colloidal dispersion is:
1. The particle size in the colloidal dispersion is larger.
2. The optical properties of the two systems, the
solution do not scatter light and therefore clear, but
colloidal dispersions scatter light thus appear turbid.
87

1.
2.
3.
The nature of the dispersing phase with respect to the
disperse phase (medium) is important.
The attraction or lack of attraction between the
disperse phase and the dispersion medium affects the
ease of preparation of colloidal dispersion and the
properties of the dispersion.
Terms used to describe the degree of attraction:
Lyophilic
solvent loving
Lyophobic
solvent hating
Amphiphilic this colloidal dispersion is formed by
association of molecules that exhibit both lyophilic
and lyophobic properties.
88
Lyophilic colloid (solvent loving)




Large organic molecules, these substances dispersed
readily upon addition to the dispersion medium to form
colloidal dispersions.
By increasing the disperse phase the viscosity increase.
And may turned to semisolid or solid dispersion,
termed a gel.
Temperature can affect the gel to be turned to solution.
Agitation also do the same and this phenomenon called
thixotrophy.
89
Lyophobic colloids (solvent hating)




Composed of inorganic particles.
When added to the dispersing phase, there is
little interaction between the two phases.
It needs some procedure to make them to
interact with the dispersion medium.
Their addition to the dispersion medium does
not affect the viscosity of the vehicle.
90




Most of the pharmaceutical preparations of colloidal
desperation and gels are aqueous preparations.
There is no general method for preparation of colloidal
dispersion, but according to the means of best suited to
the individual preparation.
Some material termed “Natural colloids” because they
are self-dispersing upon addition to the dispersing
medium. Such as Acacia.
Others require fine pulverization of coarse particles to
colloidal size by colloidal mill or micropulverizer, and
prepared under highly controlled condition. This called
Artificial colloids.
91
Amphiphilic


Amphiphilic colloids form dispersions in both
aqueous and non-aqueous media. Depending
upon their individual character and the nature of
the dispersion medium.
They generally increase the viscosity of the
dispersion medium with an increase in
concentration.
92
Terminology related to gels

A number of terms are used to describe some of the
properties of gels:
Imbibitions.
Taking up of certain amount of water without a
measurable increase in volume.
Swelling.
Taking up water with an increase in volume. Only the
liquids that solvate the gel can cause swelling.
Syneresis.
The shrinking of gel due to the great interaction between
dispersed phase while standing.
This is considered as instability (aqueous and non-aqueous
gels).
93
Thixotropy:
Is a reversible gel-sol formation with no change
in volume or temperature a type of nonNewtonian flow.
Xerogel:
Xerogel is formed when the liquid is removed
from a gel and only the framework remain.
Examples: gelatin sheets, tragacanth ribbons
and acacia tears.
94
Classification and Types of Gels
Class
Description
Examples
Inorganic
Two phase systems
Organic gel
One phase system
Hydrogel
Contain water
Silica, bentonite, sodium
alginate, methylcellulose,
alumina
Organogels
Hydrocarbon type
Petrolatum, Mineral oil,
Polyethylene gel (Plastibase)
Hydrogels
Organic hydrogels
(Natural and synthetic
gums
Pectin paste, tragacanth jelly
(Methylcellulose, sodium
carboxymethylcellulose. 95
Aluminum hydroxide gel
and bentonite magma
Carbomer and tragacanth
Preparation of Magmas and Gels

Precipitating the disperse phase, to achieve fine
degree of subdivision of the particles and a
gelatinous character to those particles.

The desired gelatinous precipitate results from the
high attraction of inorganic agents with water.

As the microcrystalline particles of the precipitate
develop, they strongly attract water to yield
gelatinous particles, which combine to form the
desired gelatinous precipitate.
96



Theses preparations remain uniform on standing with
little settling of the disperse phase. Because of the high
degree of attraction between the disperse phase and the
aqueous medium in both magmas and gels.
Other magmas and gels may be prepared by the direct
hydration in water of the inorganic chemical, the
hydrated form constituting the disperse phase.
In addition to the water vehicle, other agents as
propylene
glycol,
propylgallate
and
hydroxypropylcellulose may be used to enhance gel
formation
97
Examples of Gelling Agents

Acacia, bentonite, carbomer,
carboxymethylcellulose, sodium, cetostearyl
alcohol, colloidal silicon dioxide, ethylcellulose,
gelatin, magnesium aluminum silicate,
maltodextrin, methylcellulose, polyvinyl alcohol,
povidone, propylene carbonate, tragacanth, and
xanthan gum.
98
Carbomer (Carbopol)






It is a resin, used in a variety of pharmaceutical dosage
systems including controlled release tablets, oral
suspensions and topical gels.
It is a high molecular weight.
They are fluffy, white, dry powders with large bulk
densities.
The pH of 0.5 to 1% aqueous dispersions are
(2.7 to 3.5) and (2.5 to 3) respectively.
There are many carbomer resins, with viscosity ranges
from 0 to 80,000 cps.
Carbomer 910, 934, 934p, 940, and 1342 are official in
the USP.
99
Carbomer continued




Carbomer 934 are highly effective in thick formulation
such as viscous gels.
It can be used as suspending and emulsifying in both
oral and topical formulation, the 934 polymer is also
used to provide sustained release properties in both the
stomach and intestinal tract for commercial products.
The addition of alcohol decrease its viscosity and
clarity, so the increase in the concentrations are
required.
The maximum viscosity and clarity occur at pH7.
100
Carboxymethylcellulose





Carboxymethylcellulose can be used in
concentration of 4 to 6% of the medium
viscosity grade to produce gels.
Glycerin may be added to prevent drying.
Precipitation can occur at pH of less than 2.
It is most stable at pH level between 2 and 10.
It is incompatible with ethanol.
101
Colloidal silicon dioxide





For preparation of transparent gels.
Adsorbs large quantities of water without
liquefying.
The viscosity is largely independent of
temperature.
Change in pH may affect the viscosity.
It is most effective at pH value 7.5
102
Gelatin

Prepared from gelatin by dispersing the gelatin
in hot water followed by cooling.
Magnesium aluminum silicate, veegum

It form film at concentration of about 10% from
(Thixotropic gels).
The material is inert and has few incompatibilities
but is best used above pH 3.5.

103
Methylcellulose


It is long chain substituted cellulose that can be
used to form gels in concentrations up to 5%
Methylcellulose hydrates slowly in hot water, the
powder is dispersed with high shear in about
1/3 of the required amount of water at 80 to
90ºC
104
Examples of Magmas and Gels
Bentonite Magma, NF
 Prepared by mixing 5% bentonite, and colloidal
hydrated aluminum silicate, in purified water.
1. By adding the bentonite directly to the purified
water in a blender while running.
2. Or by sprinkling the bentonite, in portion, on
hot purified water.
 By this method the mixture allowed to stand for
24 hours for complete hydration before stirring.
105
The bentonite is swells twelve times its volume
upon addition to water.
 Bentonite after standing, it sets to a gel.
 And by agitation the solution form return.
This phenomenon is termed thixotropy.
 It is alkaline pH,
Bentonite magma is used as:
1. Suspending agent .
2. Used in extemporaneous preparations.

106
Aluminum Hydroxide gel

1.
2.
Aluminum hydroxide gel USP,
Aqueous suspension of gelatinous precipitate of
Insoluble aluminum hydroxide.
and the hydrated aluminum oxide (eq to 4% aluminum
oxide).
Preparation:

By chemical reaction, the aluminum source of the
reaction is aluminum chloride, which yield aluminum
oxide and aluminum hydroxide precipitate.
Glycerin, Sorbitol, Sucrose, Saccharin and Antimicrobial
agents.
Peppermint may added to the formula as falvorant agent.
107






It is a white, viscous suspension.
It is effective in neutralizing the gastric Hcl.
The dose 10 ml three to four times daily.
Because it possesses a trivalent cation, aluminum
hydroxide has the capability to interfere with the
bioavailability of tetracycline.
Decreasing the bioavailability of other drugs by
adsorption onto the gel.
So care should be taken to ensure the proper
dose to given to the patient.
108
Milk of Magnesia, USP






This preparation contains between 7 -8.5% of
magnesium hydroxide.
Prepared by a reaction between sodium hydroxide
and magnesium sulfate.
The preparation has a pH of 10.
Used as acid neutralizer.
Side effects the development of diarrhea.
Thus the problem of diarrhea from magnesium
hydroxide and the constipating effect from of
aluminum hydroxide, these two drugs are
combined in an antacid preparation.
109
Lubricating Jelly Formula
Methylcellulose, 4000 cps.
Carbopol 934
Propylene glycol
Methylparaben
Sodium hydroxide, qs ad
Purified water
0.8%
0.24%
16.7%
0.015%
pH 7
100 %
110
Preparation
1.
2.
3.
4.
5.
6.
Disperse the methylcellulose in 40 ml of hot water.
Chill overnight in a refrigerator to effect solution.
Disperse the Carbopol 934 in 20 ml of water.
Adjust pH to 7.
Dissolve Methylparaben in propylene glycol.
Mix the methylcellulose, Carbopol and propylene glycol
fractions with care to avoid incorporation of air.
Uses:
To assist in medical procedures, to aid in inserting of
various devices and drugs, including catheters and
suppositories, and as a vehicles for some drug products.
111
Methods of preparation





There are two possible methods, with the dry
gum method being the most popular:
Dry gum method of preparation.
Look on page 132
Wet gum method of preparation.
Look on page 132.
112
Pharmaceutical application of
Emulsions




Oral, rectal, and topical administration of oils
and oil-soluble drugs.
To enhance palatability of oils when given orally
by disguising taste and oiliness.
They can increase absorption of oils and oil
soluble drugs through intestinal walls.
Intramuscular injections of some water-soluble
vaccines to provide slow release.
113



Parenteral nutrition formulated as emulsion.
Sterile oil-in water emulsions are used to deliver
oily nutrients intravenously to patients, using
non-toxic emulsifying agents, such as lecithin.
Examples cod liver oil emulsion, liquid paraffin
oral emulsion and castor oil emulsion.
Examples of emulsions for external use are
Turpentine Liniment BP and oily calamine
lotion BP.
114
Emulsions types

Oil in water (O/W).

Water in Oil (W/O).

Multiple emulsion

Water in oil and all in water (W/O/W).
For delay-action of drug delivery systems.
If the emulsion is for oral or i.v administration it will
always be oil-in water.

Oil in water and all in oil (O/W/O).
115
Emulsion for External use:

The therapeutic use, texture and patient
acceptability will be taken place into account.

Oil in water emulsion are less greasy, easily
washed from the skin and more cosmetically
acceptable than water in oil.

They have an occlusive effect, which hydrates
upper layers of skin called an emollients.

Water in oil emulsions rub in more easily.
116
Identification of emulsion type




Miscibility tests.
Conductivity measurements.
Staining tests.
Dye tests.
117
Formulation of Emulsions

An ideal emulsion has globules of disperse phase
that retain their initial character, that is the mean
size does not change and the globules remain
evenly distributed.

The formulation of emulsions involves the
prevention of coalescence of the disperse phase
and reducing creaming.
118
What causes emulsions to crack or cream?










Incorporation of excess disperse phase as discussed above.
Globule size. Stable emulsions require a maximal no of small sized
(1-3µm) diameter globules, and as few as larger(15-20µm) diameter
globules.
Storage temperature.
Potential for globule coalescence. Increasing the viscosity of the
continuous phase will reduce the potential for globule coalescence as
this reduces the movement of globules.
Changes which affect the interfacial film formed by the emulsifying
agent. These changes may be chemical, physical or biological effects:
Microbiological contamination may destroy the emulsifying agent.
Addition of a common solvent.
Addition of an emulsifying agent.
Addition of a common solvent.
Addition of an emulsifying agent of opposite type, for instance
cationic to anionic.
119
Dispensing emulsions





Emulsions can be prepared in small scale using mortar
and pestle. Electric mixers can also be used.
Incorporation of excess air may be a problem.
All equipment must be clean and dry.
All oil-soluble and water soluble components of the
emulsion are separately dissolved in the appropriate
phase.
A suitable emulsifying agent must then be chosen.
120
Quantities for primary emulsions
Type of oil
Examples
Fixed
Oil
water
Gum
Almond, arachis, cod liver oil, 4
castor
2
1
Mineral
(Hydrocarbon)
Liquid paraffin
3
2
1
Volatile
Turpentine, cinnamon,
peppermint
2
2
1
Oleo-resin
Male fern extract
1
2
1
121
122
123
124
125
126
Theories of Emulsification



Surface-tension theory.
Oriented-wedge theory. Block
Plastic or interfacial film theory.
127
1. Surface tension theory

All liquids have a tendency to assume a shape
having the least amount of surface area exposed.

For a drop of a liquid, it is a spherical shape.

In the spherical drop of liquid there are internal
forces which promote the association of the
molecules to resist the distortion of the drop
into a less spherical form.
128
Theory continued

If two or more drops of the same liquid come
into contact with one another, the tendency is
for them to join or to coalesce, making one large
drop having less surface area.

This tendency of liquids may be measured
quantitatively, and when the surrounding of the
liquid is air, it is referred to as Liquid’s surface
tension.
129

When a liquid is in contact with a second liquid in
which it is insoluble and immiscible, the force
causing each liquid to resist breaking up into
smaller particles is called interfacial tension.

Substances that can promote the lowering of this
resistance to break up and encourage a liquid to
be reduced to smaller drops or particles.

These substances is called
Surface Active Agent.
130

Thus surface active agent facilitate the breaking up
of large globules into smaller ones. Which then
have lesser tendency to form coalesce.
131
2. Oriented-wedge theory



Assume monomolecular layers of emulsifying
agent curved around a droplet of the internal
phase of the emulsion.
Certain emulsifying agents orient themselves
about and within a liquid in a manner reflective of
their solubility in the particular liquid.
In a system containing two immiscible liquids,
presumably the emulsifying agent would be
preferentially soluble in one of the phases and
would be embedded more deeply and strongly in
that phase then the other.
132
Oil
Water
133





This theory based on:
emulsifying agent have a hydrophilic or water
loving portion and a hydrophobic or oil loving
portion.
The molecules will position themselves into each
phase.
Depending on the shape and size of the
molecules, their solubility characteristics and their
orientation,
the wedge-shape arrangement envisioned for the
molecules will cause the surrounding of either oil
globules or water globules.
134
Wedge theory continued


Emulsifying agent having greater hydrophilic
character than hydrophobic character will
promote an oil-in-water emulsion.
Emulsifying agent having a greater hydrophobic
character than hydrophilic character will
promote an water-in oil emulsion.

135

The plastic or interfacial film theory places the
emulsifying agent at the interface between the oil
and water, surrounding the droplets of the
internal phase as a thin layer of film adsorbed on
the surface of the drops.

The film prevents the contact and coalescing of
the dispersed phase.
The formation of an oil-in-water or water-in-oil
emulsion is dependent upon the degree of
solubility of the agent in the two phases.

136
Preparation of emulsions emulsifying agent.
1.
2.
3.
4.
5.
Selection of emulsifier
Must be compatible with the other formulative
ingredients, and must not interfere with the stability or
efficacy of the therapeutic effect.
Must be stable.
Non-toxic in the concentration used.
Little odor, taste or color.
The compatibility of the emulsifying agent to promote
emulsification and to maintain the stability of the
emulsion of the intended shelf life.
137
Type of emulsifiers
1. Carbohydrate materials:
Acacia, Tragacanth, Agar, Chondrus, and Pectin.
Formed oil in water emulsion
2. Protein substances.
Gelatin, Eggyolk, and Casein.
Form oil in water emulsion
3. High molecular weight alcohols
Stearyl alcohol, cetyl alcohol, and glyceryl
monostearyl alcohol.
Used as thekining agent and stabilizers for oil in
water emulsions.
138
4. Wetting agents.
May be anionic, cationic or nonionic, these agent contain
both hydrophilic and lipophilic groups.
The lipophilic group account for it’s activity:
 In anionic agents, lipophilic portion is negatively charged.
 In cationic it is positively charged.
 Non ionic show no tendency to ionize. Some of them
form oil in water, others form water in oil emulsions.
 Non ionic surfactant are effective over pH (3 to 10).
 Cationic surfactant are effective over pH range (3 to 7).
 Anionic surfactants require a pH of greater than (8).
139
5. Finely divided solids
Colloidal clays including bentonite, magnesium
hydroxide, and aluminum hydroxide.
These agents form oil in water emulsions.


The relative volume of internal and external phases of
an emulsion is important, regardless of the type of
emulsifier used.
As the internal concentration of an emulsion increased
there is an increase in the viscosity of the emulsion to
a certain point after which the viscosity decrease
sharply. At this point the emulsion
undergo inversion.
140
The HLB System



In general each emulsifying agent has a
hydrophilic and lipophilic portion with one or
the other being more or less predominant and
described the type of emulsion.
Emulsifying agents are categorized on the basis
of their chemical make-up as to their
hydrophile-lipophile balance.
Each emulsifying agent is assigned an HLB
value.
141
HLB continued




The usual range of HLB is between 1 to 20.
Material that are highly polar or hydrophilic
have higher number of HLB than materials less
polar and more lipophilic.
Those materials having an HLB value (3-6) are
lipophilic and produce W/O emulsion.
Those materials having an HLB value (8-18) are
hydrophilic and produce O/W emulsion.
See table 13. 2 for examples
142
Methods of Emulsion Preparation

1.
2.
Emulsion may be prepared in different methods
depends on:
The nature of emulsion component.
Available emulsion equipments.
In small scale a mortar and pestle Wedgewood, a
mechanical blender, a homogenizer.
In large scale, large tanks, and high speed mixer
homogenizer may be used to prepare an emulsion
143
Micro-emulsions






Thermodynamically stable.
Optically transparent.
Isotropic mixtures of a biphasic oil-water system
stabilized with surfactants.
The diameter of droplets is microemulsion may be in
the range of (100Å to 1000Å).
W/O and O/W may be formed with carefully selected
surfactant.
The type of emulsion produced depends on the oil and
surfactants used
144
145