PHARMACEUTICAL

SUSPENSIONS

(Dr.) Mirza Salman Baig

Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)
 CONTENTS
Ø Definition.

Ø Classification.

Ø Benefits & Limitations

Ø Applications

Theoretic consideration of
suspensions
•Sedimentation
•Brownian movement
•Electrokinetic properties

Ø Formulation of suspensions 2
WHY WE ARE USING SUSPENSIONS?

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The reasons for the formulation of a
pharmaceutical suspension:

when the drug is insoluble in the delivery vehicle

To mask the bitter taste of the drug

To increase drug stability

To achieve controlled/sustained drug release

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 BENIFITS

Suspension can improve chemical stability of certain drug.

E.g. Procaine penicillin G.

Ø Drug in suspension exhibits higher rate of

bioavailability than other dosage forms.

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
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 LIMITATIONS

Physical stability , sedimentation and compaction can

causes problems.

Ø It is bulky sufficient care must be taken during

handling and
Ø transport.

Ø It is difficult to formulate.

Ø Uniform and accurate dose can not be

achieved unless suspension are packed in unit
dosage form.
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 Features Desired In Pharmaceutical
Suspensions
Ø The suspended particles should not settle rapidly and
sediment produced, must be easily re-suspended by the use
of moderate amount of shaking.

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

Ø It should have pleasing odour , colour and palatability.

Ø Good syringeability.

Ø It should be physically,chemically and microbiologically

stable.

Ø Parenteral /Ophthalmic suspension should be sterilizable.

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WHAT ARE SUSPENSIONS?

2016-9-19
 DISPERSE SYSTEM

• The term "Disperse System" refers

to a system in which one substance
(The Dispersed Phase) is
distributed, in discrete units,
throughout a second substance (the
continuous Phase ).

• Suspensions are heterogenous

system consisting of 2 phases.

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A solid in liquid dispersion, in which the
particle size is more than colloidal size.

DISPERSE SYSTEM

DISPERSION MEDIUM DISPERSED PHASE

oAqueous / oily liquid oInsoluble solid

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 Definition

Ø A Pharmaceutical suspension is a coarse dispersion in

which internal phase (therapeutically active
ingredient)is dispersed uniformly throughout the
external phase.

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Ø The internal phase consisting of
insoluble solid particles having a range
of size(0.5 to 5 microns) which is
maintained uniformly through out the
suspending vehicle with aid of single
or combination of suspending agent.

Ø The external phase (suspending

medium) is generally aqueous in some
instance, may be an organic or oily
liquid for non oral use.

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Classification
•Based On rout of administration
Oral suspension
Externally applied suspension
Parenteral suspension

• Based On Electrokinetic Nature Of

Solid Particles
Flocculated suspension
Deflocculated suspension

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 Deflocculation and flocculation
(Flocculated Suspensions)
In flocculated suspension, formed flocs (loose
aggregates) will cause increase in sedimentation
rate due to increase in size of sedimenting particles.

Ø Hence, flocculated suspensions sediment more

rapidly.

Ø Here, the sedimentation depends not only on the

size of the flocs but also on the porosity of flocs.

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Deflocculated suspensions

Ø In deflocculated suspension, individual

particles are settling.

Ø Rate of sedimentation is slow , which

prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.

Ø This phenomenon called ‘caking’ or

‘claying’.

Ø In deflocculated suspension larger particles

settle fast and smaller remain in supernatant
liquid so supernatant appears cloudy.
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 Theory of Suspensions
• Sedimentation Behaviour
• Sedimentation means settling of particle or
floccules under gravitational force in liquid
dosage form.

• Velocity of sedimentation expressed by

Stokes Equation

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 Stokes Equation

• Where, vsed. = sedimentation velocity in cm / sec

• d = diameter of particle
• ρ s= density of disperse phase
• ρ o= density of disperse media
• g = acceleration due to gravity
• η = viscosity of disperse medium in poise

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Limitation of Stoke’s Equation .

Stoke's equation applies only to:

Spherical particles in a very dilute suspension

(0.5 to 2 gm per 100 ml)

Ø Particles which freely settle without collision .

Ø Particles with no physical or chemical

attraction.

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Sedimentation Parameters

Sedimentation volume (F) or height

(H) for flocculated suspensions:
Definition:
Sedimentation volume is a ratio of the
ultimate volume of sediment (Vu) to the
original volume of sediment (Vo)
before settling.
F = Vu / Vo
Where,
Vu = final or ultimate volume of sediment
Vo = original volume of suspension before settling

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F has values ranging from less than one to greater
than one.

When F < 1 Vu < Vo

When F =1 Vu = Vo

The system is in flocculated equilibrium and show no

clear supernatant on standing.

When F > 1 Vu > Vo

Sediment volume is greater than the original volume
due to the network of flocs formed in the suspension
and so loose and fluffy sediment

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The sedimentation volume gives only a qualitative
account of flocculation.

Fig : Suspensions quantified by sedimentation

volume (f)
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Degree of flocculation (β)
It is the ratio of the sedimentation volume of
the flocculated suspension ,F , to the
sedimentation volume of the deflocculated
suspension, F∞

ß = F / F∞

(Vu/Vo) flocculated
ß = --------------------
(Vu/Vo) deflocculated

Ø The minimum value of ß is 1,when

flocculated suspension sedimentation
volume is equal to the sedimentation
volume of deflocculated suspension.
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.

Brownian Movement

Brownian movement of particle prevents

sedimentation by keeping the dispersed material in
random motion.

Ø Brownian movement depends on the density of

dispersed phase and the density and viscosity of
the disperse medium.

Ø The kinetic bombardment of the particles by the

molecules of the suspending medium will keep the
particles suspending, provided that their size is below
critical radius (r).
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 Electro kinetic Properties

The zeta potential is defined as the difference in

potential between the surface of the tightly bound layer
(shear plane) and electro-neutral region of the solution.

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Ø Zeta potential has practical application in stability
of systems containing dispersed particles .

Ø If the zeta potential is reduced below a certain

value, the attractive forces exceed the repulsive
forces, and the particles come together.

Ø This phenomenon is known as flocculation

Ø The flocculated suspension is one in which zeta

potential of particle is -20 to +20 mV

Ø Thus the phenomenon of flocculation and

deflocculation depends on zeta potential carried
by particles.

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 :
FORMULATION OF SUSPENSIONS

Ø The formulation of a suspension depends on

whether the suspension is flocculated or deflocculated.

Ø Three approaches are commonly involved

1. Use of structured vehicle

2. Use of controlled flocculation
3. Combination of both of the methods

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 Structured vehicle
Ø Structured vehicles called also thickening or
suspending agents.
Ø They are aqueous solutions of natural and synthetic
gums.
Ø It is applicable only to deflocculated suspensions.
E.g. methyl cellulose, sodium carboxy methyl
cellulose,
acacia, gelatin and tragacanth.
Ø These structured vehicles entrapped the particle and
reduces the sedimentation of particles.
Ø Thus, the use of deflocculated particles in a structure
vehicle may form solid hard cake upon long storage.

Ø Structured vehicle is not useful for Parenteral

suspension because they may create problem in
syringeability due to high viscosity. 27 27
 INGREDIENTS FOR

FORMULATION OF SUSPENSIONS

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VISCOSITY :-
Viscosity is a measure of a fluid's
resistance to flow.
It describes the internal friction of a
moving fluid.
A fluid with large viscosity resists motion
because its molecular makeup gives it a
lot of internal friction.
A fluid with low viscosity flows easily
because its molecular makeup results in
very little friction when it is in motion.
 1) Suspending agents
Suspending agent are also known as hydrophilic
colloids which form colloidal dispersion with Water
and increase the viscosity of the continous phase.
Ø Suspending agent form film around particle and
decrease interparticle attraction.
Ø Most suspending agents perform two functions
i.e. besides acting as a suspending agent
they also imparts viscosity to the solution.
Ø Preferred suspending agents are those that give
thixotropy to the media such as Xanthan gum,
Carageenan
Eg. Methylcellulose, Hydroxyethylcellulose,
Carboxymethylcellulose, Microcrystalline cellulose, Acacia,
Tragacanth, Carbomer, Gelatin
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 SURFACE TENSION
"Surface tension is a contractive
tendency of the surface of a fluid
that allows it to resist an external
force."
FORMULA USED TO CALCULATE SURFACE
TENSION :-

Where,
Where,  γ = surface tension
 θ = contact angle
 ρ = density
g = acceleration due to gravity
r = radius of tube
 2) Wetting Agents

Hydrophilic materials are easily wetted by water while

hydrophobic materials are not.

Ø However hydrophobic materials are not easily

wetted by Water (polar liquids)

Ø The extent of wetting by water is dependent on the

hydrophillicity of the materials.

Ø If the material is hydrophobic then it is difficulty to

wet by water.

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.

3) Surfactants
Surfactants decrease the interfacial tension between
drug particles and liquid thus liquid is penetrated in
the pores of drug particle displacing air from them and
thus ensures wetting.
Ø Generally, we use non-ionic surfactants

Ø Polysorbate 80 is most widely used due to its

following advantages

§ It is non-ionic so no change in pH of
medium
§ No toxicity. Safe for internal use.

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 4) Solvents

The commonly used solvents used are glycerin,

polyethylene glycol and polypropylene glycol.

Ø The mechanism by which they provide wetting is that

they are miscible with water and reduce liquid air
interfacial tension.

Ø Liquid penetrates in individual particle and facilitates

wetting.

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 5) Osmotic Agents
They are added to produce osmotic pressure
comparable to biological fluids when suspension is
to be intended for ophthalmic or injectable preparation.

Ø Most commonly used osmotic agents are

Ø dextrose,
Ø mannitol
Ø sorbitol.
Ø sodium chloride,
Ø sodium sulfate
Ø glycerol.

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 6) Preservatives

Ø Naturally occurring suspending agents such as

tragacanth, acacia,
xanthan gum are susceptible to microbial
contamination.

Ø This leads to:

§ loss in suspending activity of suspending

agents,
§ loss of color, flavor and odor,
§ change in elegance etc.

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Name of Concentration
preservatives range

Propylene glycol 5-10%

Disodium EDTA 0.1%
Benzalkonium chloride 0.01-0.02%
Benzoic acid 0.1%
Butyl paraben 0.006-0.05% oral
suspension
0.02-0.4% topical
formulation

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 7) Flavoring And Coloring Agents
Ø They are added to increase patient acceptance.

Ø Only sweetening agent are not capable of

complete taste masking of unpleasant drugs therefore,
a flavoring agents are incorporated

Ø E.g.
Mint Ginger Sarsaparilla
syrup
Anise oil Glucose Spearmint oil
Benzaldehyde Glycerin Thyme oil

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 8) Coloring agents 

Colors are obtained from natural or synthetic sources.

Ø Plant colors are most widely used for oral suspension.

Ø The synthetic dyes should be used within range

of( 0.0005 % to 0.001%)
Ø Color aids in identification of the product.

Ø Brilliant blue (blue)

Ø Indigo carmine(blue)
Ø Amaranth (red)
Ø Tartarazine (yellow)

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   9) Sweetening Agents

They are used for taste masking of bitter

drug particles.
Bulk sweeteners

Sugars such as Sucrose, xylose, ribose, glucose,

mannose.

Sugar alcohols such as sorbitol, xylitol, mannitol

A bulk sweeteners is used at concentration
of 15-70 %
Artificial sweetening agents

Sodium cyclamate, Sodium saccharin, Aspartame

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 10) Humectants

Humectants absorb moisture and prevent

degradation of API by moisture.

Ø Examples of humectants most commonly used in

suspensions are propylene glycol , glycerol

Ø Total quantity of humectants should be

between 0-10 % w/w.

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 11) Antioxidant
Ascorbic acid derivatives such as ascorbic acid,
erythorbic acid,

Ø Thiol derivatives such as thio glycerol, cytosine,

acetylcysteine,
Ø
Ø Tocopherols

Ø Butylated hydroxy anisole(BHA)

Ø Butylated hydroxytoluene (BHT)

Ø Sodium bi sulfite,

Ø Sodium sulfateacetone
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.

Wetting agents They are added to disperse solids in

continuous liquid phase.
Flocculating They are added to floc the drug
agents particles
Thickeners They are added to increase the
viscosity of suspension.

Buffers They are added to stabilize the

and pH adjusting agents suspension to a desired pH range.

Osmotic They are added to adjust osmotic

agents pressure comparable to biological
fluid.
Coloring They are added to impart desired
agents color to suspension and improve
elegance.
Preservatives They are added to prevent microbial
growth.
External They are added to construct
liquid vehicle structure of the final suspension.
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 Label

2016-9-19
 Label

2016-9-19