SUSPENSIONS

Suspension:

Definition
A Pharmaceutical suspension is a coarse
dispersion in which internal phase is dispersed
uniformly throughout the external phase.
The internal phase consisting of insoluble solid
particles which is maintained uniformly through
out the suspending vehicle with aid of single or
combination of suspending agents.
The external phase (suspending medium) is
generally aqueous in some instance, may be an
organic or oily liquid for non oral use.

Suspension:

(500 um)

Classification of suspensions:
1- Based On General Classes
Oral suspension e.g. antacid, antibiotic
Externally applied suspension e.g.lotion
Parenteral suspension
Ophthalmic suspension
2- Based On Proportion Of Solid Particles
Dilute suspension (2 to10% w/v solid)
Concentrated suspension (50% w/v solid)
3- Based On Electrokinetic Nature Of Solid
Particles
Flocculated suspension
Deflocculated suspension

Advantages And Disadvantages

Advantages:

1- Used for 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:
l
Reduce the contact time between solid drug
particles and dispersion media increase the
stability of drug like Ampicillin by making it as
reconstituted powder.
A drug that degraded in the presence of water
suspended in non-aqueous vehicles.
Examples are phenoxymethypencillin/ coconut oil and
tetracycline HCL/ oil
l

Advantages And Disadvantages

3- Drug in suspension exhibits higher rate of bioavailability
than several dosage forms. bioavailability is in
following order,
Solution > Suspension > Capsule > Compressed
Tablet
>
Coated
tablet
4- Suspension can mask the unpleasant/ bitter taste of
drug. E.g. Chloramphenicol
5- Some materials are needed to be present as finely
divided forms to increase the surface area.
For example, Mg carbonate and Mg trisilcate are used to
adsorb some toxins

Advantages And Disadvantages

6-Suspension can be used for topical applications:
An example is calamine lotion Bp after evaporation of
dispersing media; the active agent will be left as light
deposit
7- Can be used for parentral administration
intramuscular (i.m.) to control rate of absorption
8- In vaccines
9- X-ray contrast media:
an example is oral and
propyliodone

rectal

administration

of

10-In aerosol suspension of active agents in mixture of

propellants

Advantages And Disadvantages

Disadvantages
1-Physical
stability,
sedimentation
compaction can causes problems.

and

2-It is bulky, sufficient care must be taken during

handling and transport.
3-It is difficult to formulate
4-Uniform and accurate dose can not be achieved
unless suspension are packed in unit dosage
form

Features Desired In Pharmaceutical

Suspensions
1-The suspended particles should not settle rapidly and
sediment produced, must be easily re-suspended by
the use of moderate amount of shaking.
2-It should be easy to pour yet not watery and no
grittiness.
3-It should have pleasing odour, colour and palatability.
4-Good syringeability.
5-It should be physically,chemically and microbiologically
stable.
6-Parenteral/Ophthalmic
sterilizable.

suspension

should

be

FACTORS TO BE CONSIDERED
I. Particle size control:
- Particle size of any suspension is critical and must be
reduced within the range as determined during the
preformulation study.
-Too large or too small particles should be avoided.
Larger particles will:
A- settle faster at the bottom of the container
B- particles > 5 um impart a gritty texture to the product
which may cause irritation if injected or instilled to the
eye
C- particles > 25 um may block the needle
-Too fine particles will easily form hard cake at the bottom
of the container.

FACTORS TO BE CONSIDERED
II. Wetting of the particles
-

Hydrophilic materials (talc, ZnO, Mg2CO3) are easily

wetted by water while hydrophobic materials (sulphur,
charcoal) are not due to the layer of adsorbed air on the
surface. Thus, the particles, even high density, float on
the surface of the liquid until the layer of air is displaced
completely.

The use of wetting agent allows removing this air from

the surface and to easy penetration of the vehicle into
the pores.

However hydrophobic materials are easily wetted by

non-polar liquids.

FACTORS TO BE CONSIDERED

FACTORS TO BE CONSIDERED
I-wetting agents include:
1-Surfactants
-Surfactants decrease the interfacial tension between drug
particles and liquid and thus liquid is penetrated in the pores
of drug particle displacing air from them and thus ensures
wetting.
- Surfactants of HLB value 7 9 are used as wetting agents.
-Disadvantages of surfactants are:
A- that they have foaming tendencies.
B- they are bitter in taste.
C-Some surfactants such as polysorbate 80 interact with
preservatives such as methyl paraben and reduce
antimicrobial activity.

FACTORS TO BE CONSIDERED
- Polysorbate 80 is most widely used surfactant both for
parenteral and oral suspension formulation.
- Sodium laurylsulphate is used for external application.
2-Hydrophilic Colloids
-

Hydrophilic colloids coat hydrophobic drug particles in

one or more than one layer. This will provide
hydrophillicity to drug particles and facilitate wetting.

Disadvantage:They cause deflocculation of suspension

because force of attraction is declined.

e.g. acacia, tragacanth, alginates, gelatin, wool fat, egg

yolk, bentonite, Veegum, Methylcellulose etc.

FACTORS TO BE CONSIDERED
3-Solvents
The most commonly used solvents
used are alcohol, glycerin, polyethylene
glycol and polypropylene glycol.

The mechanism by which they provide

wetting is that solvent flows into the
voids between particles to displace air
and it coats and separates the material
so that water can penetrate and wet the
particles.

FACTORS TO BE CONSIDERED
III. Sedimentation:
Sedimentation means settling of particle or
floccules occur under gravitational force in
liquid dosage form.
- Velocity of sedimentation expressed by Stokes
equation:

FACTORS TO BE CONSIDERED
Where, vsed.
= sedimentation velocity in cm / sec
d = Diameterof particle
r = radius of particle
s= density of disperse phase
o= density of disperse media
g = acceleration due to gravity
o = viscosity of disperse medium in
poise

FACTORS TO BE CONSIDERED
According to the Stoke's equation, the velocity of
sedimentation of particles in a suspension can be
reduced by:
1- decreasing the particle size

2- by minimizing the difference between the densities of

the particles and the vehicle.
The density of the vehicle of a suspension can be
increased by adding the following substances either
alone or in combination: polyethylene glycol, polyvinyl
pyrolidone, glycerin, sorbitol, and sugar.
3-The velocity of sedimentation decreases as the viscosity
of the vehicle increases.
The viscosity and density of any vehicle are related to
each other.

FACTORS TO BE CONSIDERED

Sedimentation Parameters

1- Sedimentation volume (F) or height (H) for

flocculated suspensions:
Definition: Sedimentation volume is a ratio of the final or
ultimate volume of sediment (Vu) to the original volume
of sediment (VO)
before settling.

F = V u / VO
Where, Vu = final or ultimate volume of sediment
VO = original volume of suspension before settling.

FACTORS TO BE CONSIDERED

F has values ranging from less than one to greater than one.
normally F < 1

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

Sediment Volume

FACTORS TO BE CONSIDERED
2-Degree of flocculation ()

Degree of flocculation: is the ratio of the

sedimentation volume of the flocculated suspension,
F, to the sedimentation volume of the deflocculated
suspension, F

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

FACTORS TO BE CONSIDERED

When the total volume of both the flocculated

and the deflocculated suspensions are same;

= (Vu)floc / (Vu)defloc
-The minimum value of is 1; this is the case
when the sedimentation volume of the
flocculated suspension is equal to the
sedimentation
volume
of
deflocculated
suspension.
- is more fundamental parameter than F since
it relates the volume of flocculated sediment to
that in a deflocculated system

FACTORS TO BE CONSIDERED
IV. Brownian Movement

Brownian
movement
of
particle
prevents
sedimentation by keeping the
dispersed material in random
motion.

Brownian Movement

Brownian movement depends

on the density of dispersed
phase and the density and
viscosity of the disperse
medium.
The kinetic bombardment of
the
particles
by
the
molecules of the suspending
medium
will
keep
the
particles
suspending.

2-5 m

FACTORS TO BE CONSIDERED
V. Electrokinetic
Properties
Zeta Potential
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.

FACTORS TO BE CONSIDERED

The ions that gave the particle its charge, are

called potential-determining ions.
Immediately adjacent to the surface of the
particle is a layer of tightly bound solvent
molecules,
together
with
some
ions
oppositely
charged
to
the
potentialdetermining ions.
These two layers of ions at the interface
constitute a double layer of electric charge
(shear plane).

FACTORS TO BE CONSIDERED

Zeta potential governs the degree of repulsion

between the adjacent, similarly charged,
dispersed particles.
If the zeta potential is reduced below a certain
value, the attractive forces exceed the
repulsive forces, and the particles come
together. This phenomenon is known as
flocculation.
Particles carry charge may acquire it from
adjuvants as well as during process like
crystallization, grinding processing, ionization
of functional group of the particle, adsorption
of ions from solution e.g. ionic surfactants.

FACTORS TO BE CONSIDERED
VI. 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.
Hence,
flocculated
sediment more rapidly.

suspensions

Here, the sedimentation depends not

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

flock

FACTORS TO BE CONSIDERED

In flocculated suspension the loose structure

of the rapidly sedimenting flocs tends to
preserve in the sediment, which contains an
appreciable amount of entrapped liquid.
The volume of final sediment is thus relatively
large and is easily redispersed by agitation.

Even the smallest particles are involved in

flocs, so the supernatant appears clear.

FACTORS TO BE CONSIDERED
Deflocculated suspensions
In deflocculated suspension, individual particles are
settling.
rate of sedimentation is slow.
which prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.

This phenomenon called cacking or claying.

In deflocculated suspension,
larger particles settle fast and
smaller remain in supernatant liquid
so supernatant appears cloudy

cake

A comparison of properties of flocculated and

defloccuated suspension particles

Sedimentation behaviour of flocculated

and deflocculated suspensions

FACTORS TO BE CONSIDERED
Flocculating agents:
1.
Electrolytes
(e.g. Nacl, sulfate, citrates, phosphates salts)
reduce the zeta potential surrounding the solid particles.
This leads to decrease in repulsion potential and makes
the particle come together to from loosely arrange
structure (floccules).
-

The flocculating power increases with the valency of the

ions. As for example, calcium ions are more powerful
than sodium ions because the velency of calcium is two
whereas sodium has valency of one.

EX:

bismuth

subnitrate

with

KH2PO4

Caking Diagram

Caking Diagram

In 1st caking zone :

Addition of KH2PO4in +ve zeta potential (owing to
adsorption of negatively charged phosphate anion)
which accompanied by in Vu/Vo

In Non caking zone:

KH2PO4 More reduction in Zeta zone
( ~ zero) while Vu/Vo remain unchanged (approached the
plateau)

In 2nd caking zone:

KH2PO4 zeta potential in negative direction till
becomes sufficient to re-induce deflocculated suspension
while Vu/Vo

FACTORS TO BE CONSIDERED
2.Surfactants

Both ionic and non-ionic surfactants can be used to bring

about flocculation of suspended particles.
Ionic surfactants: cause neutralization of the charge on
each particle. The particles are then attracted towards to
each other by van der waals forces and forms loose
agglomerates.
Non-ionic surfactant: they are adsorbed on to more than
one particle thus forming a loose flocculated structure.

FACTORS TO BE CONSIDERED
3. Polymers (e.g. alginate, starch, cellulose derivatives)

Polymers possess long chain in their structures. The part

of the long chain is adsorbed on the surface of the
particles and remaining part projecting out into the
dispersed medium. Bridging between these later
portions, also leads to the formation of flocs.
P ro jec tion out into
d isp ersion m ed ium

S o lid p artic le

A dsorption o n th e
surfa ce of pa rticles

S olid p ar ticle

F orm a tion of b ridge be tw e en partic les

FACTORS TO BE CONSIDERED
VI. Viscosity Of Suspensions
Viscosity
of
suspensions
is
of
great
importance
for
stability
and
pourability
of
suspensions.
As we know suspensions have least physical stability
amongst all dosage forms due to sedimentation and cake
formation.
As the sedimentation is governed by Stokes law,

v=d2 (s - l ) g/18
So as the viscosity of the dispersion medium increases, the
terminal settling velocity decreases yielding higher
stability to the suspension.

FACTORS TO BE CONSIDERED

On the other hand as the viscosity of the

suspension
increases,
its
pourability
decreases and inconvenience to the patients
for dosing increases.
Thus, the viscosity of suspension should be
maintained within optimum range to yield
stable and easily pourable suspensions.

FACTORS TO BE CONSIDERED

Different Approaches To Increase The Viscosity Of Suspensions:

1-Viscosity Enhancers
- Some natural gums (acacia, tragacanth),
- polymers, cellulose derivatives (sodium CMC, methyl
cellulose)
- clays(bentonite)
- sugars (glucose, fructose)

2- Co-solvents
- Some solvents which themselves have high viscosity
are used as co-solvents to enhance the viscosity of
dispersion medium.
3- Structured vehicles
This part will be dealt in detail latter.

Method of preparation:
The preparation of suspension includes three
methods:
(1) use of controlled flocculation
(2)
use of structured vehicle
(3) combination of both of the two pervious
methods.
The following is the general guidelines to
suspension formulation:

Method of preparation

Method of preparation:
A-Structured vehicle
Structured vehicles called also thickening or suspending
agents.

They are aqueous solutions of natural and synthetic

gums.

These are used

suspension.

It is applicable only to deflocculated suspensions.

to

increase

the

viscosity

of

the

E.g. Methyl cellulose, sodium carboxymethyl cellulose,

acacia, gelatin and tragacanth.
These
are
non-toxic,
pharmacologically inert,
and
compatible with a wide range of active and inactive
ingredients.

Method of preparation:

These structured vehicles entrapped the particle and

reduces the sedimentation of particles.
Thus, the use of deflocculated particles in a structure
vehicle may form solid hard cake upon long storage.

Note that too high viscosity isnt desirable:

a-it causes difficulty in pouring and administration.
b-it may affect drug absorption since they adsorb on the
surface of particle and suppress the dissolution rate.

- Structured vehicle is not useful for Parenteral suspension

because they may create problem in syringeability due to
high viscosity.

Method of preparation:
B-Controlled flocculation
Controlled flocculation of particles is obtained by
adding flocculating agents, which are:
(1)-electrolytes (2)- surfactants (3)- polymers
C-Flocculation in structured vehicles
Sometimes suspending agents can be added to
flocculated suspension to retard sedimentation
Examples of these agents are:
Carboxymethylcellulose (CMC), Carbopol 934,
Veegum, and bentonite

Evaluation of suspensions:
Suspensions are evaluated by determining their
physical stability.
Two useful parameters for the evaluation of
suspensions are;
A- sedimentation volume
B- degree of flocculation.

The determination of sedimentation volume

provides a qualitative means of evaluation.
A quantitative knowledge is obtained by
determining the degree of flocculation.