SUSPENSION

SUSPENSION
• A pharmaceutical suspension may be defined as a coarse dispersion
containing finely divided insoluble material suspended in a liquid
medium.
• The physical chemist defines the word “suspension” as two-phase
system consisting of an undissloved or immiscible material
dispersed in a vehicle (solid, liquid, or gas).
• Generally pharmaceutical suspensions contain aqueous dispersion
phase however in some cases they may be an oily or organic phase.
• The suspensions have dispersed particles above the colloidal size
that is mean particle diameter above 1µm.
Examples of Pharmaceutical Suspensions

Antacid oral suspensions Antibacterial oral suspension

Dry powders for oral suspension (antibiotic)

Analgesic oral suspension

Anthelmentic oral suspension

Anticonvulsant oral suspension

Antifungal oral suspension

 Pharmaceutical applications of suspensions
1. Insoluble drug or poorly soluble drugs which required to be given orally
in liquid dosage forms ( in case of children, elderly, and patients have
difficulty in swallowing solids dosage forms)
2. To over come the instability of certain drug in aqueous solution:
a) Insoluble derivative formulated as suspension
An example is oxytetracycline HCL (instable)  calcium salt (stable)
a) Reduce the contact time between solid drug particles and
dispersion media  increase the stability of drug like Ampicillin by
making it as reconstituted powder.
b) A drug that degraded in the presence of water  suspended in
non-aqueous vehicles. Examples are phenoxymethypencillin/
coconut oil and tetracycline HCL/ oil
3. To mask the taste:
Examples are paracetamol suspension (more palatable) and
chloramphenicol palmitate.
 Pharmaceutical applications of suspensions
4. Some materials are needed to be present as finely divided forms to
increase the surface area. Fore example, Mg carbonate and Mg
trisilcate are used to adsorb some toxins
5. Suspension can be used topical applications:
An example is calamine lotion BP  after evaporation of dispersing
media; the active agent will be left as light deposit
6. Can be used for parentral administration  intramuscular (i.m.) to
control arte of absorption
7. In vaccines Absorbed antigen

Aluminum hydroxide

e.g. Diphtheria and Tetanus vaccines

8. X-ray contrast media: an example is oral and rectal administration of

propyliodone
9. In aerosol  suspension of active agents in mixture of propellants
 Advantages
• Suspension can improve chemical stability of certain drug.
E.g.Procaine penicillin G

• Drug in suspension exhibits higher rate of bioavailability than

other dosage forms. bioavailability is in following order,

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

• Duration and onset of action can be controlled. E.g.Protamine

Zinc-Insulin suspension

• Suspension can mask the unpleasant/ bitter taste of drug. E.g.

Chloramphenicol
 Disadvantages
• Physical stability, sedimentation and compaction can causes
problems.

• It is bulky sufficient care must be taken during handling and

transport.

• It is difficult to formulate

• Uniform and accurate dose can not be achieved unless

suspension are packed in unit dosage form
 Classification
• Based On General Classes
– Oral suspension
– Externally applied suspension
– Parenteral suspension
• Based On Proportion Of Solid Particles
– Dilute suspension (2 to10 percnt; w/v solid)
– Concentrated suspension (50 percnt; w/v solid)
• Based On Electrokinetic Nature Of Solid Particles
– Flocculated suspension
– Deflocculated suspension
• Based On Size Of Solid Particles
– Colloidal suspension (< 1 micron)
– Coarse suspension (>1 micron)
– Nano suspension (10 ng)          
 Flocculation & deflocculation

Flocculated Non-flocculated
Particles forms loose aggregates and form a Particles exist as separate entities
network like structure
weakly bonded to form fluffy conglomerates Repulsion energy is high
Rate of sedimentation is high Rate of sedimentation is slow
Sediment is rapidly formed Sediment is slowly formed
Sediment is loosely packed and doesn’t form Sediment is very closely packed and a hard
a hard cake cake is formed
Sediment is easy to redisperse Sediment is difficult to redisperse
Suspension is not pleasing in appearance Suspension is pleasing in appearance
The floccules stick to the sides of the bottle They don’t stick to the sides of the bottle
Clear supernatant Cloudy supernatant
Features Desired In Pharmaceutical Suspensions
• The suspended particles should not settle rapidly and sediment
produced, must be easily re-suspended by the use of moderate
amount of shaking.

• It should be easy to pour yet not watery and no grittiness.

• It should have pleasing odour, colour and palatability.

• Good syringeability.

• It should be physically, chemically and microbiologically stable.

• Parenteral/Ophthalmic suspension should be sterilizable.

 Formulation Additives
In addition to vehicle, stabilizer, sweetening and flavouring agents, which are
common in liquid dosage forms, the following additives are required to prepare
suspensions which include:
1. Suspending and Thickening agents
2. Wetting Agents
3. Dispersing agent
4. Flocculating Agent

1. Suspending and Thickening agents: They are added with the objective to
increase apparent viscosity of the continuous, phase thus preventing rapid
sedimentation of the dispersed particles.
a) Natural Polysaccharides :Gum acacia, Tragacanth, sod. Alginate, Xanthan
Gum
b) Semi-Synthetic Polysaccharides: Sodium Carboxymethyl cellulose, Methyl
cellulose, Hydroxypropyl methyl cellulose, microcrystalline cellulose
c) Clays: Aluminium Magnesium Silicate, Bentonite, Hectorite
d) Synthetic Agents: Carbomer, Colloidal Silicon dioxide
 Formulation Additives
2. Wetting Agents: Wetting agents are additives which are usually added to
decrease this hydrophobicity. These agents generally get adsorbed at the
solid-liquid interface and promote wetting of the solid particles by the liquid
of the dispersion medium.
a) Surfactants: polysorbates, sorbitan, esters, sodium lauryl sulfate,
sodium dioctyl sulfosuccinate
b) Hydrophilic Polymers: acacia, bentonite, colloidal silicon dioxide and
cellulose derivatives
c) Hydrophilic Liquids: alcohol, glycerol, propylene glycol
3. Dispersing agent: These additives are generally added as an aid to uniform
distribution and dispersion of solid particles of the dispersed phase. Wetting
agents such as surfactants are often employed as dispersing agents.
4. Flocculating Agent: These are substances added to cause controlled
aggregation of the particles of the dispersed phase in a suspension.
Examples of such agents include surfactants, electrolytes and hydrophilic
polymers.
 Method of preparation

Addition of wetting agent & dispersion medium

Uniform dispersion of deflocculated particles

A B C
Addition of
flocculating agent
Addition of
flocculating agent
Incorporation of
structured vehicle
Flocculated
suspension

Flocculated suspension
Incorporation of
as final product structured vehicle

Deflocculated Flocculated suspension

suspension in structured in structured vehicle as
vehicle as final product final product
 Formulation of Suspensions
• Suspensions containing diffusible solids
• Suspensions containing indiffusible solids
• Suspensions containing poorly wettable
solids
• Suspensions of precipitate forming liquids
• Suspensions produced by chemical reactions
• Suspensions containing diffusible solids consist of solids insoluble in
water but easily wettable.

• On shaking with water solid particles diffuse readily through out the liquid
and remain suspended for a long time.

• The suspensions containing diffusible solids are prepared by triturating

the solids in a mortar with sufficient quantity of vehicle to form a smooth
cream.

• Any soluble nonvolatile substance is then added by separately dissolving

them in a small quantity of vehicle.

• More vehicles are then added and any foreign particle is strained through
a muslin cloth.

• Any volatile component is added at this stage and adding the required
quantity of vehicle makes up the final volume.

• Example: Magnesium Trisilicate Mixture

• Suspensions containing indiffusible solids consist
of substances, which do not remain distributed in
the dispersion medium when shaken for long
time to ensure uniformity of dose.

• They are prepared by adding a suitable

thickening agent to the vehicle, which increases
the viscosity of the vehicle and delays the
separation or sedimentation of indiffusible
particles.

Example: Calamine Lotion

• Suspensions containing poorly wettable solids
consist of substances, which are poorly soluble,
and at the same time poorly wetted by the
dispersion medium, and clump together with the
difficulty to disperse.

• They are prepared by including suitable wetting

agent in the formulation. These agents get
adsorbed at the solid/liquid interface and
promote wetting of the solid particles by the
liquid of the dispersion medium.

• Example: Sulphur Lotion

• Suspensions of precipitate forming liquids
consist of liquid tinctures which are alcoholic
or hydroalcoholic extract of vegetable drugs
which contain resinous material.
• When tinctures are added to water they
precipitate. Precipitates are indiffusible and
stick to the walls of the container.
• They are prepared by adding a suitable
thickening agent prior to the addition of the
precipitate forming liquid.

Example: Lobelia and Stramonium Mixture

• Suspensions produced by chemical reactions are
prepared by mixing two dilute solutions of
reactants to form a fine precipitate.

• Generally precipitates so formed are diffusible and

no suspending agent is required.

• If precipitate is indiffusible a suitable thickening or

suspending agent may be added.

• They are prepared by dissolving the reactants

separately in approximately half volumes of the
vehicle and the two portions are then mixed
together.
• Example: Zinc Sulphide Lotion
 Preparation of Suspensions
• Reduce drug powder to desired size
• Add drug and wetting agent to solution
• Prepare solution of suspending agent
• Add other ingredients
– electrolytes, color, flavor
• Homogenize medium
• Package
 Structured Vehicle
• Structured vehicles called also thickening or suspending agents. They are
aqueous solutions of natural and synthetic gums. These are used to increase the
viscosity of the suspension.
• Methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose,
acacia, gelatin and tragacanth are the most commonly used structured vehicle
in the pharmaceutical suspensions. These are non-toxic, pharmacologically
inert, and compatible with a wide range of active and inactive ingredients.
• These structured vehicles entrapped the particle and reduces the sedimentation
of particles. Although, these structured vehicles reduces the sedimentation of
particles, not necessarily completely eliminate the particle settling. Thus, the
use of deflocculated particles in a structure vehicle may form solid hard cake
upon long storage.
• The risk of caking may be eliminated by forming flocculated particles in a
structured vehicle.
• Note that too high viscosity isn’t desirable and it causes difficulty in pouring and
administration. Also, it may affect drug absorption since they adsorb on the
surface of particle and suppress the dissolution rate.
• Structured vehicles are pseudoplastic or plastic in their rheological behaviors
Preparation Of Structured Vehicle
• Structured vehicles are prepared with the help of
Hydrocolloids.
• In a particular medium, they first hydrolyzed and swell to
great degree and increase viscosity at the lower
concentration. In addition, it can act as a ‘Protective colloid’
and stabilize charge.
• Density of structured vehicle also can be increased by:
– Polyvinylpyrrolidone
– Sugars
– Polyethylene glycols
– Glycerin
 Packaging and Storage of Suspensions
1. Should be packaged in wide mouth containers having
adequate air space above the liquid.
2. Should be stored in tight containers protected from:
freezing, excessive heat & light
3. Label: "Shake Before Use" to ensure uniform
distribution of solid particles and thereby uniform
and proper dosage.
4. Stored in room temperature if it is dry powder (25
0
C). It should be stored in the refrigerator after
opening or reconstitute (freezing should be avoided
to prevent aggregation)
 Stability of Suspensions
A-Physical stability
– Appearance, color, odor and taste
– pH
– Specific gravity
– Sedimentation arte
– Sedimentation volume
– Zeta potential measurement
– Compatibility with container
– Compatibility with cap liner
– Microscopic examination
– Determination crystal size
– Determination uniform drug distribution
B-Chemical stability:
– Degradation of active ingredient
– Viscosity change
– antimicrobial activity:
• Incompatibility with preservative
• Degradation of preservative
• Adsorption of preservative onto drug particle
 Stability of Suspensions
• The physical stability of a pharmaceutical suspension is the condition in
which the particles do not aggregate and in which they remain uniformly
distributed throughout the dispersions.
• In order to achieve this ideal situation the suspension should have
additive, which are added to achieve ease in resuspension by a moderate
amount of agitation.
• Taking a case example: In case of dispersion of positively charged particles
that is flocculated by addition of an aninonic electrolyte like monobasic
potassium phosphate. The physical stability of the system is enhanced by
addition of carboxymethylcellulose, Carbopol 934, veegum, tragacanth or
bentonite either alone or in combination. No physical incompatibility is
recorded as majority of hydrophilic colloids are negatively charged and
are compatible with anionic flocculating agents.
• When a flocculated suspension of negatively charged particles with a
cationic electrolyte is prepared (aluminum chloride) the addition of
hydrocolloid may result in an incompatible product resulting in stingy
mass, which has no suspending action, and settle rapidly. In such a
condition protective agent is added to change the sign on the particles
from the negative to positive is employed which can also be achieved by
the adsorption onto the particle surface by fatty acid amine or gelatin.
• Thus an anionic electrolyte is used to produce floccules that are
compatible with negatively charged suspending agent.
Routes of administration of suspension

• Suspensions are used to administer insoluble and

distasteful substances in a form that is pleasant to
taste by providing a suitable form, for the application
of dermatological materials to the skin and mucous
membrane and for parenteral usage.

• Thus suspensions can be administered by oral,

topical,
topical parenteral and ophthalmic application
 Oral suspensions
• Patients who have problems in swallowing solid dosage forms require
drugs to be dispersed in a liquid.

• Oral suspensions permit the formulation of poorly soluble drugs in the

form of liquid dosage form.

• As these suspensions are to be taken by oral route therefore they

must contain suitable flavoring and sweetening agents.

• Drugs, which possess unpleasant taste in solution dosage form like

paracetamol, chloramphenicol palmitate etc. can be formulated as
palatable suspension as they are suitable for administration to
peadiatric patients.

• Finely divided solids like kaolin, magnesium carbonate etc., when

administered in the form of suspensions will be available to a higher
surface area for adsorptive and neutralizing actions in the
gastrointestinal tract.
 Topical suspensions
• These suspensions are meant for external application
and therefore should be free from gritty particles.

• There consistency may range from fluid to paste.

• Example of fluid suspension includes calamine lotion,

which leave a deposit of calamine on the skin after
evaporation of the aqueous dispersion phase. Zinc
cream has a consistency of semisolid. Zinc cream
consists of high percentage of powders dispersed in an
oily (paraffin) phase.
 Parenteral suspensions
• These suspensions should be sterile and should possess
property of syringability.

• Parenteral suspensions are also used to control the rate

of absorption. As the absorption rate of the drug is
dependent on the dissolution rate of the solid.
Therefore by varying the size of the dispersed solid
particles the duration and absorption can be controlled.

• Vaccines are also formulated as dispersions of killed

microorganisms for example in Cholera vaccine or as
toxoid adsorbed on to substrate like aluminium
hydroxide or phosphate for prolonged antigenic
stimulus. For example adsorbed Diphtheria and Tetanus
toxoid.
 Ophthalmic suspensions
• These should also be sterile and should possess very
fine particles.

• Drugs, which are unstable in aqueous solution, are

formulated as stable suspensions using non-aqueous
solvents.

• For example fractioned coconut oil is used for

dispersing tetracycline hydrochloride for ophthalmic
use