Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.

; Tolentino, Rochel Angela 3EPH

Chapter 27- Suspension & Emulsion
Coarse suspension- dispersion of finely divided insoluble solid particles (disperse phase) in a fluid
(dispersion medium/ continuous phase)
Colloidal dispersion- disperse phase with a mean particle diameter of up to 1 m
Ex: Aluminum hydroxide suspension and Magnesium hydroxide suspension
For coarse dispersions, it consists of solid in liquid dispersion where particles are bigger than
colloidal size
Emulsion- two immiscible liquids where one is finely subdivided and uniformly distributed as droplets
throughout the other; stabilized by adding emulsifying agent
Physical properties of well-formulated suspensions & emulsions:
Product must remain homogenous for at least the period between shaking the container and
obtaining the required amount.
Should sediment or creaming occur, it must be easily re-suspended by moderate agitation.
Product may be thickened to reduce settling rate of particles or creaming rate of oil globules.
However, resulting viscosity must not be so high so that removal of product from container and
transfer to site of application will not be difficult.
Suspended particles should be small and uniformly sized in order to produce a smooth, elegant
product, free from a gritty texture.
Pharmaceutical applications of suspensions:
Suspensions are administered as oral dosage forms, topically to the skin, eye or mucous membrane
surfaces, or parenterally by injection.
1. Suspensions as oral drug delivery systems
- Many people have trouble swallowing solid dosage forms, hence requires a drug to be dispersed
in a liquid.
-

Moreover, some materials are required to be present in the gastrointestinal tract in a finely
divided form, therefore their formulation as suspensions are preferred as they will provide the
desired high surface area.
Ex: Solids such as Kaolin, Magnesium carbonate and Magnesium trisilicate are used for
adsorption of toxins or to neutralize excess acidity. A dispersion of finely divided silica in
dimethicone 1000 is used in veterinary practice in treating frothy bloat.

Taste of most drugs is more noticeable in solution form rather than in an insoluble form.
Ex: Paracetamol is available both as a solution and a suspension for pediatric patients, but the
latter is more palatable and therefore more appropriate for children.

2. Suspensions for topical administration

- They can be fluid preparations (e.g. Calamine lotion) which leaves a light deposit of the active
ingredient on the skin even after the evaporation of the dispersion medium.
- Some are in the form of pastes, which are semi-solid in consistency and have high
concentrations of powders dispersed, usually in a paraffin base.
- Suspending a powdered drug in an emulsion base is also possible, just like in the case of Zinc
cream.
3. Suspensions for parenteral use and inhalation therapy
- Suspensions parenterally administered are used to control the rate of absorption of the drug.
Duration of the activity of the drug can be controlled by altering the size of the dispersed
particles. Absorption rate of the drug in the blood stream depends on its rate of dissolution.
Ex: If the drug is suspended in a fixed oil such as arachis or sesame, the product will remain
after injection in the form of an oil globule which will present to the tissue fluid a minimal
surface area from which the partitioning of drug can occur. On the other hand, drugs suspended
in aqueous vehicle will be released faster as diffusion of the product may occur along muscle
fibers and become miscible with tissue fluid.

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
-

Vaccines for immunity induction are often formulated as dispersions of killed microorganisms
(e.g. cholera vaccine). However, injectable versions of which are now replaced by orally
delivered suspensions. Alternatively, constituent toxoids can be adsorbed on to a substrate of
aluminum hydroxide or phosphate, as in adsorbed diphtheria and tetanus vaccine. Thus a
prolonged antigenic stimulus is provided, resulting to a high antibody titre.

Some x-ray contrast media are also formulated in this way. Ex: Barium sulfate- available as an
oral suspension or for rectal administration, is used or the examination of the alimentary tract.
Propyliodone- dispersed in either water or arachis oil, is used for the examination of bronchial
tract.

Adsorptive properties of fine powders are also used in the formulation of inhalations.
Ex: Volatile components of menthol and eucalyptus oil would be lost from solution very rapidly,
whereas a more prolonged release is obtained if they are adsorbed on to a light magnesium
carbonate prior to preparation of a suspension.

Solubility and stability consideration

- Some drugs are poorly soluble in a suitable solvent, hence the need to formulate a suspension
arises.
Ex: Hydrocortisone acetate and Neomycin eye drops are formulated as suspensions due to the
poor solubility of hydrocortisone in a suitable solvent.
- Degradation of a drug in the presence of water may prevent its use as an aqueous solution,
therefore it may be needed to synthesize a derivative that can be formulated as a suspension.
- Contact between the solid drug particles and the dispersion medium can be lessened by
preparing the suspension immediately prior to administration.
Ex: Amoxicillin is provided as trihydrate salt mixed with other powder/ granulated ingredients;
the pharmacist then reconstitutes the product to required volume with water immediately prior
to use, allocating a 7 or 14 day shelf life at a temperature below 25C.
Formulation of Suspensions
A. Particle Size Control
-It is necessary that the drug to be suspended is of fine particle size prior to formulation as this will
ensure slow sedimentation of the particles. Large particles (>5 m diameter) will impart a gritty texture
and may cause irritation when injected or instilled in the eyes. The size and shape of the particle is
important in ensuring the ease of administering parenteral suspension, also it is possible to block a
hypodermic needle with particles over 25 m diameter, especially if they are acicular in shape rather than
isodiametric.
-Though the particle size of a drug may be small when the product is manufactured, there is
always a degree of crystal growth which occurs on storage especially when temperature fluctuations occur.
This is caused by the increase of the solubility of the drug as temperature rises, but upon cooling the drug
will crystalize out. This is common with slightly soluble drugs such as Paracetamol.
-If drugs are polydispersed, the very small crystals of less than 1 m will exhibit greater solubility
than larger ones. Over a period of time, small crystals will become even smaller while large particles will
increase; hence it is advantageous to use a suspended drug of narrow size range. Addition of surfaceactive agents or polymeric colloids may also help prevent crystal growth.
-Different polymorphic forms of a drug exhibit different solubilities, the metastable state is the most
soluble. Conversion of the metastable, in solution, to the less soluble stable state, and its subsequent
precipitation, will lead to changes in particle size.
B. Use of wetting agents
-Some insoluble solids are easily wetted by water and will readily disperse throughout the aqueous
phase with minimal agitation, but most will have different hydrophobicity and will not be easily wetted.
Some will form large porous clumps within the liquid, while others remain in the surface and attaches to
the upper part of the container. The foam produced on shaking will be slow to subside due to the
stabilizing effect of the small particles at the liquid/air interface.
-To ensure adequate wetting, the interfacial force between the solid and the liquid must be reduced
so that the adsorbed air can be displaced from the solid surfaces by the liquid. The particles then disperse
throughout especially when an intense shear action is applied in mixing. If a number of suspensions are

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
created with different range of concentrations, the concentration to be chosen will be the lowest which
yields adequate wetting.
Most widely used wetting agents:
a. Surface-active agents
-Surfactants with an HLB value between 7 and 9 are suitable as wetting agents. Hydrophobic
particle surfaces would adsorb hydrocarbon chains while polar groups project into the aqueous
medium and become hydrated. Wetting reduces the interfacial tension between both the solid and
the liquid, and between the liquid and the air. Most surfactants are used at concentrations up to
0.1% and include, for oral use, the polysorbates (Tweens) and sorbitan esters (Spans). For external
use, sodium lauryl sulfate and sodium dioctylsulfosuccinate may be used. The choice of surfactant
for parenteral is limited, but the main ones used are the polysorbates, some of poloxamers
(polyoxyethylene/ polyoxypropylene copolymers) and lecithin. The disadvantages of using this type
of wetting agent include excessive foaming and the possible formation of deflocculated system.
b. Hydrophilic colloids
-These act as protective colloids by coating the solid hydrophobic particles with a multimolecular
layer, imparting a hydrophilic character and so will promote wetting. These include acacia,
bentonite, tragacanth, alginates, xanthan gum, and cellulose derivatives. These materials are also
used as suspending agents and may produce deflocculated system especially if used at low
concentrations.
c. Solvents
-These solvents penetrate the loose agglomerates of powder, displacing the air and so enabling
wetting to occur. These materials include alcohol, glycerol, and glycols which are water miscible
and will reduce liquid/air interfacial tension.
C. Flocculated and deflocculated systems
-Having added a suitable wetting agent, one must determine whether a suspension is flocculated or
deflocculated and decide which is more desirable. Whether or not it is flocculated or deflocculated
depends on the magnitudes of the forces of repulsion and attraction between the particles.
-In a deflocculated system, the dispersed particles remain as discrete units and settling will be slow.
The supernatant in this system remains cloudy for an appreciable time after shaking due to the slow
settling rate of the smallest particles even though the larger ones have sedimented. The repulsive forces
between each particle allow them to slip past each other as they sediment. The slow rate of settling
prevents entrapment of liquid within the sediment, which thus becomes compacted and can be very
difficult to redisperse. This is called caking or claying which is the most serious physical stability problem
in suspension formulation.
-The aggregation of particles in flocculated system will lead to a faster rate of sedimentation
because each unit is composed of several individual particles which makes it larger. The rate of settling
will depend on the porosity of the aggregate. If it is porous, the dispersion medium can flow through and
around each aggregate or floccule as it sediments. The supernatant liquid in this system quickly turns
clear as the large flocs which settles rapidly are composed of particles of different sizes.
-Deflocculated systems have the advantage of slow sedimentation rate, hence it will provide
uniform dose taken from the container. But when settling does occur, sediment is compact and hard to
redisperse. Flocculated systems on the other hand, form loose sediments which are easier to redisperse
but sedimentation is rapid which may cause inaccurate dosing and may alter the appearance of the
product.

Controlled flocculation
This is usually achieved by a combination of particle size control, the use of electrolytes to control
zeta potential and the addition of polymers to enable crosslinking to occur between particles.
A deflocculated system with a high viscosity is an ideal formulation. Underflocculation will yield
undesirable properties of deflocculated systems, while an overflocculated will make a product look
elegant, but will require a very high viscosity to minimize settling, which in turn may cause
difficulty in redispersion.
Flocculating agents

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH

Electrolytes- the addition of inorganic electrolytes to an aqueous suspension alters the zeta
potential of the dispersed particles and a sufficiently low value of this may cause flocculation.
Surfactants- Ionic surface-active agents may also flocculation by neutralizing the charge on each
particle, thus resulting in a deflocculated system.
Polymeric flocculating agents- Starch, alginates, cellulose derivatives, tragacanth, carbomers, and
silicates are examples of polymers used to control flocculation. Their linear branched- chain
molecules form a gel-like network within the system and become adsorbed on to the surfaces of
the dispersed particles, thus holding them in a flocculated state.

Rheology of suspensions
An ideal pharmaceutical suspension would exhibit a high apparent viscosity at low rates of shear so
that, on storage, the suspended particles would either settle only very slowly or, preferably, remain
permanently suspended.
Viscosity Modifiers
Polysaccharides
Acacia- used as suspending agent due to its action as protective colloid; not a good thickening
agent; used in preparations of resinous materials (precipitate upon addition of water); it is rarely
used in preparations for external use due to its stickiness
Tragacanth- forms viscous aqueous solutions; used as thickening agent due to its thixotropic and
pseudoplastic properties; it is stable over a pH range 4-7.5 but takes 7 days to hydrate fully after
dispersion of water.
Alginates- Alginic acid (polymer of D-mannuronic acid, is prepared from kelp. It must not be heated
above 60C as depolymerization occurs with a consequent loss in viscosity; most viscous; exhibit
maximum pH range of 5-9 and at low pH, the acid id precipitated; Manucol, or sodium alginate, is
widely used material
Starch- rarely used suspending agent; one of the constituents in tragacanth powder and can also
be used with carmellose sodium
Xanthan gum (Keltrol)- anionic heteropolysaccharide from Xanthomonas campestris on corn sugars;
very soluble in cold water; widely used thickening agent of suspensions for oral use; stable over
wide pH range
Water- soluble celluloses
Methylcellulose (Celacol, Methocel)- [C 6H7O2(OH2)OCH3]n; semi-synthetic polysaccharide with
several grades available depending on degree of methylation and chain length; the longer the
chain, the more viscous; more soluble in cold than in hot water resulting in dispersing in warm
water and cooling it through constant stirring; non-ionic and stable at wide pH range
Hydroxyethylcellulose ( Natrosol)- available in different viscosity grades; soluble in both cold and
hot water;exhibits same properties as methylcellulose
Carmellose sodium (sodium carboxymethylcellulose)- [C 6H10-xO5(CH2COONax]n ;viscosity depends
on n which represents degree of polymerization
Microcrystalline cellulose ( Avicel)-partially hydrolyzed cellulose and is made up of crystal which are
readily dispersed in water(but are not soluble) to produce thixotropic gels; widely used suspending
agent;can
be
improved
upon
incorporation
of
hydroxycolloid
(carboxymethylcellulose,methylcellulose or hydroxypropyl methylcellulose)
Hydrated silicates
Bentonite- [Al2O3.4SiO2.H2O]; used at concentrations of up to 2-3% in preparations for external use
such as calamine lotion
Magnesium aluminum silicate (Veegum)- attapulgite, disperses and swells readily in water by
absorbing the aqueous phase into its crystal phase;several grades available,differ in particle
size;can be used both internally and externally up to about 5%;stable at pH range of 3.5-11;exhibit
thixotrophy and plasticity
Hectorite- can be used at concentration of 1-2% for external use;obtains synthetic hectorite
(Laponite) which do not exhibit batch variability
Carbomers
- totally synthetic copolymer of acrylic acid and allyl sucrose;used in concentration up to 0.5% for
external use;forms acidic,low-viscosity solutions when dispersed in water;becomes highly viscous when pH
is adjusted to pH of between 6 and 11

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
Colloidal silicon dioxide (Aerosil)
- will aggregate when dispersed in water and form 3D network; can be used up to 4% for external
use;thickening agent for non-aqueous suspensions
Types of Emulsions
- Emulsion is a mixture of aqueous phase with various oils/waxes.

Oil-in-water is when oil droplets are dispersed in water

Water-in-oil is when water droplets are dispersed in oil
Tests in identification of emulsion type
Miscibility test with OIW- emulsion will only be miscible with liquids that are miscible with its
continuous phase
Conductivity measurements systems with aqueous phase will readily conduct electricity, whereas
systems with oily continuous phase will not
Staining tests- either water-soluble or an oil-soluble dye is blended with the emulsion. Microscopic
examination shows the continuous phase or the dispersed droplets
Formulation of Emulsions
The final choice of emulsifying agents to be used in the formulation of a particular product will
depend extensively on the properties and use of the final product and the other materials required to be
present.
Choice of Emulsion Type
The decision on which type of emulsion either o/w or a w/o will eliminate the inappropriate
emulsifying systems. For the oral administration of fats and oils, either as medicament or as a vehicle or
solvent adjunct for oil-soluble drugs, are formulated as oil-in-water emulsions. This makes them pleasant
and the inclusion of a flavorant will disguise the unpleasant taste. For IV administration, the emulsion must
be on an o/w type. On the other hand, IM injections must be formulated as w/o products if the watersoluble drug is required for depot therapy.
Emulsions are widely used dosage forms for external applications of drugs. Semi-solid emulsions
are called as creams and the more fluid preparations are called either lotions, or if intended for
massage they are called liniments. Oil-in-water emulsions are used for the topical application of watersoluble drugs. They are non-greasy, hence, they are pleasant to use and easily washed by water from the
surface of the skin. Water-in-oil emulsions, on the other hand, have an occlusive effect by inhibiting the
evaporation of eccrine secretions. T
Choice of Oil Phase
Typically, the oil phase of an emulsion is the active agent and therefore its concentration in the
product should be predetermined. The common examples of medicaments which are formulated as
emulsions for oral administration are liquid paraffins, castor oil, cod liver oil, and arachis oil. Cottonseed
oil, soya bean oil, and safflower oil are used for IV feeding because of their high calorific value. Turpentine
oil and benzyl benzoate are common examples of oils formulated as emulsions and applied externally.
Emulsions for external use incorporate oil as carriers of the active ingredient. The oil must have an
effect on the viscosity and transport of the drug from the emulsion. Liquid paraffin is the most commonly
used oil for this purpose. They are used to control the consistency of the emulsion. They also ensure that
the product can be easily spread on skin and sufficiently viscous to form a coherent film over the skin.
Moreover, the inclusion of beeswax, carnauba wax, or high fatty alcohols and other waxes can also modify
the film-forming capabilities of the emulsion. Barrier creams (many are formulated as w/o) form continuous
films that are sufficiently tough and flexible to prevent contact between the skin and aqueous based
irritants. Silicone oils, such as 10-20% dimethicone, which have exceptional water repellent properties,
permit the the formulation of equally effective counterpart of the barrier creams. Various vegetable oils,
such as arachis, sesame, cottonseed, and maize oils, are also available. Oils that are expressed from the
seeds or fruits have high protein content and contain vitamins and minerals. They are formulated for oral
administration as emulsions. They also lack toxicity allowing their use for both internal and external
purposes.
Emulsion Consistency

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
The texture or the feel of the emulsion must be considered. A w/o has a greasy texture and it has a
higher relative viscosity than o/w emulsions. Greasy texture gives a feeling of richness to many cosmetic
formulations. Oil-in-water emulsions are non-greasy and has no sticky feeling when applied on the skin.
They are more readily absorbed in the skin because of the its lower oil content and it is easily washed by
water. Emulsions must exhibit plasticity or pseudoplasticity and thixotrophy. High apparent viscosity at
very low rates of shear caused by movement of disperse-phase globules is necessary to retard this
movement and maintain the stability of the emulsionLow viscosity lotions and liniments can be formulated
that are dispensed from a flexible plastic container via a nozzle. Light shearing is required and this is
useful for painful or inflamed skin conditions. Main disadvantage with low viscosity emulsions is their
tendency to cream easily, especially if formulated with low oil concentration. Emulsions with high apparent
viscosity for external use are termed as creams and they have semi-solid consistency. They are usually
packed into collapsible plastic or aluminum tubes. Large volumes of high viscosity products are packed in
jars or glass.
Several Methods in Which Rheological Properties Can Be Controlled
Volume Concentration of the Disperse Phase
The viscosity of the product as a whole would be higher than the viscosity of the continuous phase
on its own. Hence, as the concentration of disperse phase increases, so does the apparent viscosity of the
product. Disperse phase concentration must not exceed 60% of the total because phase inversion may
occur.
Particle Size of the Disperse Phase
It is possible to increase viscosity of an emulsion by a reduction in mean globule diameter and this
can be achieved by homogenization. Particle size of the dispersed system is controlled mainly by method
and conditions of manufacture of the emulsion and by the type of emulgent used. Two mechanisms for this
occurrence: (1) a smaller mean globule size can cause increased flocculation and in flocculated systems
there is a significant part of the continuous phase that is trapped within aggregates of droplets, (2) if a
hydrophilic colloid is used as stabilizer it will form a multi-molecular film around the dispersed globules,
thus, a reduction of mean globule size will increase the total surface area.
Viscosity of the Continuous Phase
There is a direct relationship between the viscosity of the emulsion and the continuous phase.
Syrup and glycerol are used as sweetening agents and will increase the viscosity of the continuous phase.
But their main disadvantage is that they increase the density difference of the 2 phases thus accelerating
creaming. Hydrocolloids, when used as a stabilizing agent, will form multi-molecular layers around the
dispersed globules but also by increasing the continuous phase viscosity. If oil is the continuous phase, use
soft or hard paraffin waxes increase viscosity.
Nature and concentration of the emulsifying system
Surface-active agents will influence the degree of flocculation by forming linkages between the
adjacent globules and creating gel-like structure.
Choice of Emulsifying Agent
Toxicity and Irritancy
For internal use emulsions, the use of non-ionic surfactants which are natural and semi-synthetic
derivatives such as polysaccharides, glyceryl esters, cellulose esters, and polysorbates. They have the less
tendency to irritate and less toxic than their anionic counterpart. Ionic emulsifiers must not be used for
oral emulsions because of their irritant and laxative effect at concentrations necessary for emulsification.
Non-ionic surfactants are suitable for parenteral use such as lecithin, polysorbate 80, methycellulose,
gelatin, and serum albumin.
Formulation by HLB method
Complex interfacial films formed by a blend of an oil-soluble emulsifying agent and a water soluble
emulsifier will produce most satisfactory emulsions. HLB method is the most useful method for calculating
relative amount of emulsifiers for a particular o/w emulsion. Higher number indicates that it is polar or
hydrophilic, while lower numbers indicate non-polar or lipophilic surfactants. Trial and error is the method
of choosing the best combination of emulsifying agent to be used in the formulation. Condensed films are
produced by emulgents having long, saturated hydrocarbons, thus providing cohesion between adjacent

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
molecules. Disadvantages of HLB method include the inability to take into account the effect of
temperature, the presence of additives and the concentration of the emulsifier.
Use of Phase-Inversion Temperature
The o/w emulsion stabilized by non-ionic emulsifier upon heating, undergoes phase inversion to
form w/o emulsion. As the temperature increases, the HLB value of the non-ionic surfactant decreases as it
becomes lipophilic. At the phase inversion temperature (PIT), the emulgents have equal hydrophilic and
hydrophobic
tendencies,
thus,
phase
inversions
happen
in
this
temperature.
Classification of Emulsifying Agents
Emulsifiers ensure emulsification during manufacturing process and ensure their stability during
shelf life of the product. Emulsifiers are divided into two main classifications: (1) Synthetic or semisynthetic surface active agents and (2) naturally occurring materials and their derivatives. Synthetic and
semi-synthetic surfactants are categorized into 4 groups; namely, anionic, cationic, non-ionic, and
amphoteric. Lecithin is an amphoteric surfactants used to stabilize fat emulsions. These surfactants still
need an auxiliary non-ionic surfactant in order to form a complex monomolecular film at the oil in water
surface.
Anionic surfactants dissociate to form a negatively charged anions, which are responsible for
their emulsifying property, in aqueous solutions. They are used for external purposes only because of their
toxicity and these surfactants are relatively cheap. Alkali metal soaps and ammonium soaps include
sodium, potassium, and ammonium salts of long-chain fatty acids. They produce stable o/w emulsions that
are very efficient in alkaline medium because in acidic medium they are precipitated out as free fatty
acids. These emulsifiers are incompatible with polyvalent cations that cause phase reversal, hence, the
water to be used must be deionized. Lastly, the sodium lauryl sulfate is the most commonly used sulfated
fatty acid derivative and are used to produce stable o/w emulsions. It is used with cetostearyl alcohol to
produce emulsifying wax, which stabilizes creams and benzyl benzoate preparations.
Cationic Surfactants dissociate in aqueous solutions to form positively charged cations which is
responsible for its emulsifying property. The quaternary ammonium compounds are the most important
emulsifiers in this group. These ammonium compounds are commonly used for their disinfectant and
preservative properties and widely used in the production of o/w emulsions. Their toxicity limited their
activity in the formulation of antiseptic creams. Cetrimide (cetryl trimethylammonium bromide) is one of
the most useful cationic surfactants available and used in concentrations within 0.5% with 5% cetostearly
alcohol for the formulation of cetrimide cream.
Nonionic surfactants include oil-soluble compounds that can stabilize w/o emulsions and watersoluble compounds that can stabilize o/w emulsions. They are commonly used because they are less toxic
and less irritating to the skin and mucus membrane. They are used to prepare oral and parenteral
emulsion products. They also exhibit great compatibility with various materials and less sensitive to the
presence of electrolytes. It is necessary to that the polar groups are well hydrated to prevent coalescence
and compensate the lack of charge. They are composed of a fatty acid or alcohol (12-18 carbons), which
provides lipophilicity and an alcohol or ethylene group which provides the hydrophilicity in the compound.
Glyceryl monostearate, under the glycol and glyceryl esters, is a strongly hydrophobic material
that produces w/o emulsions. The addition of small amounts of sodium, potassium, or triethanolamine
salts of suitable fatty acids will produce a self emulsifying monostearate, usedful in o/w emulsions. Selfemulsifying stearin in combination with anionic soaps is used in stabilizing hydrocortisone lotion.
Sorbitan esters are produced by the esterification of one or more hydroxyl groups of sorbitan with
lauric, oleic, palmitic, or stearic acids. They have lipophilic character and tends to form w/o emulsions.
Polysorbates, on the other hand, are the polyethylene glycol derivatives of sorbitan esters. The oil and
water solubilities varies according to the type of fatty acid and number of oxytethylene grouos in the PEG
chain. They are used in conjunction with an appropriate and suitable sorbitan esters to form complex
condensed film at the water/oil surface.
Fatty alcohols polyglycol ethers are condensation products of PEG and fatty alcohols. Macrogol
cetostearyl ether or cetomacrogol 1000 are the most widely used PEG monocetyl ether. It has a high water

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
solubility and is useful as water-soluble emulsifier but it needs an oil-soluble auxiliary emulsifier in the
formulation.
In the group of fatty acid polyglycol esters, the most widely used are stearate esters or
polyoxyl stearates. Polyoxyethylene 40 stearate is a water soluble material and is used in combination
with stearyl alcohol to produce a stable emulsion. Poloalkols, on the other hand, are polyoxyethylene/
polypropylene copolymers used for as emulsifiers for intravenous fat emulsions. Lastly, higher fatty
alcohols, which includes the hexadecyl and octadecyl members are useful auxiliary emulsifiers. Their
emulsifying property may be attributed to their ability to increase the viscosity of the preparation, thereby
retarding creaming.
Naturally occurring materials have two main disadvantages: (1) show considerable batch-tobatch variation in composition (2) they are susceptible to molds and bacterial growth. They are not used in
the manufacture of products that requires long shelf-life but they are useful for extemporaneous
compounding. The most imporatant natural polysaccharide used is the acacia. It stabilizes o/w emulsions
by forming strong multimolecular film round each oil globule which retards coalescence. Creaming will
readily occur because of its low viscosity. Tragacanth and sodium alginate are also used in producing
emulsions. They are limited for internal applications only. On the other hand, semi-synthetic
polysaccharides such as methylcellulose and carmellose sodium are used as substitute to acacia. They are
useful as o/w emulsifiers.
Beeswax, wool fat, and wool alcohols are sterol-containing substances which are used in the
formulation of emulsions. Beeswax is used primarily in cosmetic cream products of both w/o (stabilizer) or
o/w type. Wool fat is composed of normal fatty acid esters of cholesterol and other sterols. They form w/o
emulsions of low-dispersed phase concentration with emollient properties. It has a characteristic odor and
the incorporation of an antioxidant is must when using wool fat. Wool fat can be converted to
polyoxyethylene lanolin derivatives which are nonionic products commonly used as o/w emulsifiers with
emollient property. Wool alcohols are the principal emulsifying agents of wool fat.
Finely divided solids can be adsorbed oil/water surface to form a coherent film that physically
prevents coalescence of the dispersed globules. If the solids are wetted by the aqueous phase then o/w
emulsion is produce while if it is wetted by the oil, a w/o emulsion is produced. Montmorillonite clay
(bentonite and aluminum magnesium silicate) and colloidal silicone dioxide are used mainly for external
use. Aluminum and magnesium hydroxides are used internally.
Other Formulation Additives
Buffers are commonly included to maintain chemical stability, to control tonicity, and to ensure
physiological compatibility. Density modifiers reduce the occurrence of density differences in the disperse
and continuous phase to attain the stability. Sucrose, dextrose, glycerol, or propylene glycol are used to
modify or correct the density in the aqueous phase. Humectants such as glycerol, polyethylene glycol, and
propylene glycol are incorporated at 5% concentrations to prevent the product form drying out after
application. They also reduce the evaporation of water, however, at high concentrations they can
dehydrate the skin. Butylated hydroxyanisole is widely used as an antioxidant and to protect fixed oils and
fats at 0.2% concentration and for essential oils up to 0.1%. The butylated hydroxytoluene is used as an
alternative to tocopherol at 10 ppm concentration to stabilize liquid paraffin. Propyl, octyl, and dodecyl
esters of gallic acid are also used as antioxidants of oils and fats. Flavorants, colors, and perfumes are
used for aesthetic properties of the final product. Sweetening agents at high concentrations may impart
Newtonian properties to the suspension. Synthetic sweeteners may adversely affect the degree of
flocculation because they are salts.
Preservation of Suspensions and Emulsions
Preservatives are essential components of an emulsion if the emulsifier used is naturally occurring
material. They prevent the growth of microorganisms. Some are sterilized if they are to be applied to a
broken skin. Bentonite may contain C. tetani and must be sterilized at 160 0C for 1 hour by autoclaving.
Solubilization by wetting agents and emulsifiers, interaction with polymers or adsorption of suspended
solids (kaolin and magnesium trisilicate), may reduce availability of preservatives.
Physical stability of suspensions

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
The physical stability of a suspension is normally tested by the measurement of its rate of
sedimentation, the final volume or height of the sediment and the ease of redispersion of the product. The
first two parameters can be assessed by the measurement of the total initial volume or height of the
suspension and the volume or height of the sediment. The ease of redispersion can be assessed by simply
agitating the product.
Physical stability of emulsions
A stable emulsion is one in which the dispersed globules retain their initial character and remain
uniformly distributed throughout the continuous phase.
Creaming- This is the separation into two regions, one if which is richer in the disperse phase than
the other. This is not a serious instability problem as a uniform dispersion can be reobtained by
shaking the product. However, creaming is undesirable because of the increased likelihood of
coalescence of the droplets. Moreover, a creamed emulsion is inelegant and if its not shaken
properly, there is a risk of incorrect dosage.
Avoidance of creaming
o Production of an emulsion of small droplet size- An efficient emulsifying agent will not
only stabilize the emulsion but also facilitate the actual emulsification process to give a
product of fine globule size.
o Increase in the viscosity of the continuous phase- Storage of the product at a low
temperature (but above freezing point) will increase viscosity of the continuous phase and
also reduce the kinetic energy of the system. This will decrease the rate of migration of the
globules of the disperse phase.
o Reduction in the density difference between the two phases- Creaming could be
prevented if the densities of the two phases were identical.
o Control of disperse-phase concentration- It is not easy to stabilize an emulsion
containing less than 20% disperse phase as creaming will readily occur. A higher dispersephase concentration would result in a hindrance of movement of the droplets and hence in a
reduction in rate of creaming.
Flocculation Prevention- Flocculation in the secondary minimum occurs readily and cannot be
avoided. Redispersion can easily be achieved by shaking. Primary minimum flocculation, however,
is more serious and redispersion is not so easy. The presence of a high charge density on the
dispersed droplets will ensure the presence of a high energy barrier, and thus reduce the incidence
of flocculation in the primary minimum.
Coalescence (breaking, cracking)- The coalescence of oil globules in an o/w emulsion is resisted by
the presence of a mechanically strong adsorbed layer of emulsifier around each globule. This is
achieved by the presence of either a condensed mixed monolayer of lipophilic and hydrophilic
emulgents or a multimolecular film of a hydrophilic material.
Chemical instability of Emulsions
Presence of electrolyte may affect the instability by:
o Reducing the energy of interaction between adjacent globules
o A salting-out effect wherein high concentrations of electrolytes can strip emulsifying agents
of their hydrated layers which results in precipitation
Oxidaiton- many of the oils and fats can be susceptible to oxidation by atmospheric
oxygen. It can be manifested by formation of degradation of unpleasant odor and taste. Can occur in
emulsifying agents such as wool fat or wool alcohols. It can be controlled by the use of antimicrobial
preservatives
Microbiological contamination- degradation of properties such as gas production, color
and odor changes, hydrolysis of fats and oils,pH changes in aqueous phase, and breaking of emulsion may
occur. Emulsion can contain bacteria and may constitute health hazard
Adverse storage conditions- may cause emulsion instability. Increase in temperature
will cause increase in the rate of creaming,increased in kinetic motion. Freezing of aqueous phase will
produce ice crystals that may exert unusual pressureson dispersed globules.
Stability of Emulsions
Methods of assessing stability

Calungsud, Karlo; Guzman, Kiana Marie; Que, Bill A.; Tolentino, Rochel Angela 3EPH
Macroscopic examination- examination of degree creaming and coalescence
Globule size analysis- if mean globule size increases, it can be assumed that coalescence is
the cause
o Viscosity changes- variation in globule size or in orientation or migration of emulsifier may
be detected by a change in viscosity; it is necessary to speed up the creaming and
coalescence to compare relative stabilities
o Accelerated stability tests
- storage at adverse temperatures- assessment of these would give a speedier
indication of a rank order of degree of instability but is essential to correlate the results with those taken
from suspensions stored at ambient temperatures
- centrifugation- suitable for artificially increasing the rate of sedimentation of a
suspension;may destroy the structure of a flocculated system
- rheological assessment-can indicate in the change of structure of the system
after various storage times
Manufacture of Suspensions
It is important to ensure that the powder to be suspended is in suitably fine degree of subdivision
to ensure adequate bioavailability,minimum sedimentation rate and impalability
Suspensions on small scale can be mixed with suspending agent through the use of mortar and
pestle. Can use wetting agent to aid dispersion.
In a larger scale, it is preferable to make concentrated dispersion of suspending agent. It is
accomplished by adding the material slowly to the vehicle while mixing
Manufacture of emulsions is important to ensure that agglomerates of the suspending agent are
fully broken up
Manufacture of Emulsions
The choice of suitable equipment for the emulsification process depends mainly on the intensity of
shearing required to produce the optimum particle size
Simple blending of oil and water with suitable emulgent system may be sufficient to produce
satisfactory emulsions
Homogenizers are often used after initial mixing to enable smaller globule sizes to be produced
Should any of the oily ingredients be of solid or semisolid consistency, they must be meltedd before
mixing
Volatile ingredients,such as flavours and perfumes, are usually added after emulsion has been
cooled
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