CHAPTER 27

SUSPENSIONS & EMULSIONS

Subgroup 9 3APharmacy
Caringal, Ebuengan, Montenegro, & Uy

INTRODUCTION
Suspension
dispersion of finely divided, insoluble solid particles (dispersed phase) in a
fluid (dispersion medium or continuous phase); solid in liquid suspension in
which particles are above the colloidal size (1um)
Emulsion
mixture of two immiscible liquids, one of which is finely subdivided and
uniformly distributed as droplets throughout the other
dispersed liquid (internal phase) usually consists of globules of diameters
down to 0.1 um which are distributed within the external or continuous phase

PHYSICAL PROPERTIES OF WELL-FORMULATED SUSPENSIONS

AND EMULSIONS
1. Product must remain sufficiently homogenous for at least the period
2.
3.
4.
5.

between shaking the container and removing the required amount

Sediment or creaming produced on storage (if any) must easily be
resuspended by moderate agitation of the container
Product may need to be thickened in order to reduce rate of the particles
or the creaming rate of oil globules
Resulting viscosity must not be so high that removal of the product from
the container and transfer to the site of application are difficult
Any suspended particles should be small and uniformly sized in order
to give a smooth, elegant product, free from gritty texture

PHARMACEUTICAL APPLICATIONS OF SUSPENSIONS

1. As oral drug delivery systems
Intended for those having difficulty swallowing solid dosage forms
Taste of most drugs is less noticeable in insoluble form rather than in solution form
2. For topical administration
Can be in the form of lotion, pastes, and creams
3. For parenteral use and inhalation
Parenteral: Employed to control rate of absorption of drug and its duration of activity
Ex: cholera vaccine, adsorbed diphtheria and tetanus vaccine, barium sulfate, and propyliodone

Inhalation:
Since volatile component is lost very rapidly from solution, a more prolonged release of volatile

components can be obtained prior to the preparation of suspension

SOLUBILITY AND STABILITY CONSIDERATIONS

If drug is poorly soluble in a suitable solvent, then formulation as suspension is

usually required
It may be possible to synthesize an insoluble derivative that can be formulated
as suspension
Prolonged contact between the solid drug particles and the dispersion medium
can be considerably reduced by preparing the suspension immediately prior to
issue to the patient

FORMULATION OF SUSPENSIONS

PARTICLE SIZE CONTROL

Drug must be of fine particle size prior to formulation to ensure slow rate of

sedimentation of suspended particles because larger particles (> 5um

diameter) will impart gritty texture and may cause irritation if injected or
instilled into the eyes
Solubility of drug may increase as the temperature rises but on cooling, the
drug will crystallize out which is a particular problem with slightly soluble drugs
(ex: paracetamol)
Inclusion of surface active agents or polymeric colloids which adsorb on to the
surface of each particle, may help to prevent crystal growth

WETTING AGENTS
Commonly Used Wetting Agents
SURFACE-ACTIVE
AGENTS

HLB value between 7 and 9 with concentrations up to 0.1%

Main surfactants used: polysorbates, some poloxamers (polyoxyethylene or polyoxypropylene
copolymers), and lecithin
Ex: polysorbates (Tweens) and sorbitan esters (Spans) for oral use; sodium lauryl sulfate and
sodium dioctylsulfosuccinate for external application
Disadvantages: excessive foaming and possible formation of a deflocculated system

HYDROPHILIC
COLLOIDS

Behave as protective colloids

Ex: acacia, bentonite, tragacanth, alginates, xanthan gum, and cellulose derivatives
Disadvantage: may produce a deflocculated system if used at low concentrations

SOLVENTS

Water miscible and reduce liquid/air interfacial tension

Penetrate the loose agglomerates of powder, displacing air from the pores of individual
particles
Ex: alcohol, glycerol, and glycols

FLOCCULATED VS DEFLOCCULATED SYSTEMS

DEFLOCCULATED SYSTEMS

Have the advantage of a slow

sedimentation rate thereby enabling

a uniform dose to be taken from the
container
However, when settling occurs, the
sediment is compacted and is
difficult to redisperse; this
phenomenon is referred to as
caking or claying

FLOCCULATED SYSTEMS

Form loose sediments which are

easily redispersible
However, the sedimentation rate
is fast and posts a danger of
inaccurate dose being
administered
Product looks inelegant

CONTROLLED FLOCCULATION
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
flocculating agents are used to convert a deflocculated to a partially
flocculated state by addition of flocculating agents

FLOCCULATING AGENTS
Commonly Used Flocculating Agents
ELECTROLYTES

Alter zeta potential of the dispersed particles; represented by Schultz-Hardy

Most widely used: sodium salts of acetates, phosphates, and citrates

SURFACTANTS

Ion surfactants cause flocculation by neutralizing the charge on each particle thus resulting
in a deflocculated system
Non-ionic surfactants have negligible effect on charge density but may adsorb onto more
than one particle thereby forming a loose flocculated structure

POLYMERIC
FLOCCULATING
AGENTS

Has linear branched-chain molecules that 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
Ex: starch, alginates, cellulose derivatives, tragacanth, carbomers, and silicates

RHEOLOGY OF SUSPENSIONS
Exhibit a high apparent viscosity at low rates of shear so that on storage,

the suspended particles would either settle slowly or preferably remain

permanently suspended
At higher rates of shear, the apparent viscosity should fall sufficiently for
the product to be poured easily from its container
If used externally, the product must spread easily without excessive dragging
but must not be so fluid that it runs off the skin surface
If intended for injection, the product should pass easily through a hypodermic
needle with only moderate pressure applied to the syringe plunger
A flocculated system partially fulfills these criteria since it exhibits a pseudoplastic or
plastic behavior whereas, a deflocculated system exhibit Newtonian behavior and even
dilatancy

VISCOSITY MODIFIERS

POLYSACCHARIDES
Examples of Polysaccharides Used
ACACIA

Often used as suspending agent for extemporaneously prepared suspensions due to its action as a protective
colloid; not a good thickening agent
Useful for preparations containing tinctures of resinous materials that precipitate on addition to water; not very
effective for dense powders and is often combined with other thickeners

TRAGACANTH

Thixotropic and pseudoplastic properties make it better thickening agent and can be used for both internal and
external products; used for extemporaneous preparation of suspensions with short shelf life; stable over pH 4-7.5

ALGINATES

Polymer of D-mannuronic acid and is prepared from kelp; suspending properties similar to tragacanth; not be
heated above 60C; exhibit maximum viscosity over pH 5-9 and at low pH the acid is precipitated
Sodium alginate (Manucol) is most widely used but is incompatible with cationic materials

STARCH

Rarely used on its own suspending agent but is one of the constituents of compound tragacanth powder; can be
used with carmellose sodium

XANTHAN GUM Anionic heteroplysaccharide produced by Xanthomonas campestris on corn sugars; very soluble in cold
water; one of the most widely used thickening agents for extemporaneous preparation of suspension for
oral use; used in concentrations up to 2% and stable over a wide pH range

WATER-SOLUBLE CELLULOSES
Examples of Water-soluble Celluloses Used
METHYLCELLULOS Semi-synthetic polysaccharide of general formula : (C 6H7O2(OH2)OCH3)n
E (Celacol, Methocel) More soluble in cold water; often dispersed in warm water and on cooling with constant stirring, a clear or
opalescent viscous solution is produced
Non-ionic, stable over a wide pH range and compatible with many ionic additives
HYDROXYETHYLCELLULOSE
(Natrasol)

Has hydroxyethyl instead of methyl groups attached to the cellulose chain; soluble both on hot and cold
water and do not gel on heating

CHEMICAL INSTABILITY OF
EMULSIONS

 Ionic emulsifying agents are usually incompatible with materials of opposite

charge.
Anionic and cationic emulgents are mutually incompatible.
Electrolyte influence the stability of an emulsion by reducing the energy of
interaction between adjacent globules and salting-out effect
Phase inversion may occur rather than demulsification.
Emulgents may be precipitated by the addition of materials in which they are
insoluble.
Changes in pH may also lead to the breaking of emulsions

OXIDATION
Oils and fats is susceptible to oxidation by atmospheric oxygen or by the

action of microorganisms.
Manifested by the formation of degradation products of unpleasant odour and
taste.
Occur with certain emulsifying agents such as wool fat or wool alcohols.
To control oxidation of:
Microbiological origin- use of antimicrobial preservatives
Atmospheric oxidation- use of reducing agents/antioxidants

MICROBIAL CONTAMINATION
Contamination of emulsions by microorganisms can
adversely affect the physicochemical properties of the
product which causes:
Gas production
Colour and odour changes
Hydrolysis of fats and oils
pH changes in the aqueous phase
breaking of the emulsion

MICROBIAL CONTAMINATION
Fungi and bacteria multiply readily in the aqueous phase of an emulsion at

room temp.
Moulds tolerate a wide pH range.
Hydrophilic colloids provide a suitable nutritive medium
Emulgents from natural sources may introduce heave contamination into
products.
Bacteria can reproduce in resin beds.
Oil-in-water emulsions are more susceptible to microbial spoilage.
Antimicrobial agent is included to prevent growth of any microorganisms that
may contaminate the product.

ADVERSE STORAGE CONDITIONS

Cause emulsion instability.
Increase in temperature cause:
Increase in rate of creaming, owing to a fall in apparent viscosity
of the continuous phase.
Increase kinetic motion.
Disperse phase will enable the energy barrier to be easily surmounted and

increase number of collisions between globules.

Emulgent will result in a more expanded monolayer leading to
coalescence.
Certain macromolecular emulsifying agents may be coagulated.

ADVERSE STORAGE CONDITIONS

Freezing of the aqueous phase will:
Produce ice crystals that may exert unusual pressures
Dissolved electrolyte may concentrate in the unfrozen water
affecting charge density on globules.
Certain emulgents may also precipitate at low temperatures.
Must be protected from the ingress of microorganisms

during manufacture, storage and use, and contain

adequate preservatives.

CLASSIFICATION OF
EMULSIFYING AGENTS

 Synthetic/ Semi-synthetic surface-active

agents
Naturally occurring materials and their
derivatives

 SYNTHETIC and SEMI-SYNTHETIC SURFACE

ACTIVE AGENTS
-depend on their ionization in aqueous solutions:
1.) Anionic
Alkali metal and Ammonium groups
Soaps of Divalent and Trivalent Metals
Amine soaps
Sulfated and Sulfonated Compounds
2.) Cationic
Quaternary ammonium compounds

3.) Non-Ionic
Glycol and Glycerol Esters
Sorbitan Esters
Fatty alcohol polyglycol esters
Fatty acid polyglycol esters
Poloxalkols
Higher Fatty alchols
4.) Ampotheric

NATURALLY OCCURING MATERIALS AND DERIVATIVES

Natural Polysaccharides
1.) Acacia
Semi-synthetic Polysaccharides
1.) Methylcellulose
2.) Carmellose Sodium
Sterol-containing substances
1.) Beeswax
2.) Wool fat
3.) Wool alcohols

PHYSICAL STABILITY OF
SUSPENSIONS

PHYSICAL STABILITY OF SUSPENSIONS

are normally assessed by:
- Measurement of its rate of sedimentation
- Final volume or height of sediment
- Ease of dispersion

STABILITY TESTING OF
EMULSIONS

METHODS OF ASSESSING STABILITY

Macroscopic examination
Examination of the degree of creaming or coalescence
Ratio of the volume of the creamed part and the total volume
Globule size analysis
Coalescence causes increase is mean globule size (decrease in globule
numbers)
Rates of coalescence by measuring changing in globule size and number.
Microscopic examination, electronic particle counting devices (ex. Coulter
counter) and laser diffraction sizing are most widely used.

METHODS OF ASSESSING STABILITY

Viscosity changes
Variation in globule size or number, or in the orientation or migration of
emulsifier.
To compare the relative stabilities of similar products, it is necessary to speed
up the processes of creaming and coalescence.
Accelerated stability test
To assess physical stability, macroscopic examination and measurement of
apparent viscosity are of value.

ACCELERATED STABILITY TESTS

Storage at adverse temperatures
Exaggerating temperature fluctuations enable to compare physical stabilities.
Temperature cycles of storage for several hours followed by refrigeration or
freezing until instability becomes evident.
Useful for the assessment of crystal growth in suspensions.
Measurement of particle size- laser diffraction or Coulter counter.
Suspension must be deflocculated so that individual particle is measured rather than each

floccule.

ACCELERATED STABILITY TESTS

Centrifugation
Suitable method for artificially increasing the rate of sedimentation.
Destroy the structure of a flocculated system that remains intact under normal
storage conditions.
Products particularly if used at speeds no faster than 200-300rpm.

ACCELERATED STABILITY TESTS

Rheological assessment
High shear rates involved destroy the structure of a suspension or emulsion.
Very low shear rates (Ex. Brookfield viscometer with Helipath stand) can give
change in the structure of the system after various storage times.
Measurement of the residual apparent viscosity after breaking down the
structure of the suspension can be used as a routine quality control procedure
after manufacture.

MANUFACTURE OF SUSPENSIONS

MANUFACTURE OF SUSPENSIONS
Powder to be suspended must initially be in a suitably fine degree of

subdivision in order to ensure adequate bioavailability, minimum sedimentation

rate and impalpability.
For extemporaneous preparation on small scale:
The powdered drug can be mixed with the suspending agent and some of the
vehicle using a pestle and mortar.
May also include a wetting agent to aid dispersion.
Other soluble ingredients should be dissolved in another portion of the vehicle,
mixed with the concentrated suspension and then made up to volume.

MANUFACTURE OF SUSPENSIONS
For larger scale:
Adding material slowly to the vehicle while mixing.
Mixers can either be an impeller type of blender or a turbine mixer.
Drug to be suspended is then added along with the wetting agent.
Other ingredients dissolved in a portion of the vehicle are added and the whole
made up to volume.
Homogenization ensures complete dispersion and produce smooth and
elegant preparation.

MANUFACTURE OF SUSPENSIONS
It is also possible to suspend an insoluble drug by precipitating it

from a solution.
used if the drug is required to be sterile but is degraded by heat or

irradiation.
By double decomposition or by altering the pH of solution, or by
precipitating the drug from a water-miscible solvent on the addition of
water
Used if the drug is required to be sterile but is degraded by heat or
irradiation.
sterilized by filtration and then precipitated to form a suspension .

MANUFACTURE OF EMULSIONS

MANUFACTURE OF EMULSIONS
Smaller the globules, slower rate of creaming.
A mean globule diameter of between 0.5 and 2.5um.
Choice of equipment depends on the intensity of shearing required, volume

and viscosity and interfacial tension

Surfactants, reduce interfacial tension, aid the process of emulsification and
promote emulsion stability.
Homogenizer can reduce globule size still further.
More intense rate of shearing can be achieved using a turbine mixer (ex.
Silverson mixer-homogenizer)

MANUFACTURE OF EMULSIONS
2 immiscible liquids in ultrasonic vibrations produce alternate regions of

compression and rarefaction

Cavities formed in rarefaction cause emulsification.
Frequency of vibration is usually produced electronically.
Mechanical methods are limited to small-scale production.
Colloid mills are for preparation on a continuous basis.
Intense shearing between rotor and stator= small globule
Other ingredients are dissolved prior to mixing particularly when making w/o
emulsions.

MANUFACTURE OF EMULSIONS
Oily ingredients must be melted before mixing.
Heating of aqueous phase to same temperature avoid premature solidification

of the oil phase.

Stirring during the cooling process to avoid demulsification.
Volatile ingredients (flavours, perfumes) must be fluid and are added after
emulsion has cooled
Alcoholic solutions or electrolytes are diluted before adding slowly and with
constant mixing.

RELEASE OF DRUGS FROM

SUSPENSION AND EMULSION
FORMULATIONS

Drug release from SUSPENSIONS

Drug is presented to the gastrointestinal fluids in a finely

divided form.
Dissolution begins immediately.
The rate of absorption of drug into blood stream is faster
than solid dosage
The more viscous, the slower the release of drug.

Drug release from SUSPENSIONS

Drugs are often formulated as suspensions for

intramuscular, intraarticular or subcutaneous injection in

order to prolong drug release which is often termed as
depot therapy.
Drug release occur more slowly if drug is suspended in an
oil that, after injection, remain as a globule, providing a
minimal area of contact with tissue fluid.
Sustained-release suspensions are less common but
example is the use of pennkinetic system.

Drug release from EMULSIONS

Oral, rectal and topical administration of oils and oil-soluble

drugs.
Lipid emulsions are widely used for intravenous feeding, choice
of emulgent is very limited and globule size must be kept below
4 micrometre diameter to avoid formation of emboli.
Can also be used as a sustained-release dosage form.
Intramuscular injection of certain water-soluble vaccines as w/o
emulsions provide a slow release of the antigen and result in
greater antibody response (longer-lasting immunity)

Drug release from EMULSIONS

Rate or release depend on o/w partition coefficient of drug

and rate of diffusion across oil phase.

w/o/w emulsion is used for prolonged release of drugs that
are incorporated into the internal aqueous phase.
o/w/o emulsions are potential sustained-release bases.
Multiple emulsions tend to be stable only for a relatively
short time but polymers are use as alternatives to improve
their physical stability.

END