Pharmaceutical

suspensions
 Definition
• A Pharmaceutical suspension is a coarse dispersion in which
internal phase ( therapeutically active ingredient )is dispersed
uniformly throughout the external phase.
• 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.
• The external phase ( suspending medium ) is generally
aqueous in some instance, may be an organic or oily liquid for
non oral use.
 Advantages of Suspension
Useful for drugs having low solubility.  -1
2-Drug in suspension exhibits higher rate of
bioavailability when compared with capsules and
tablets
3-Duration and onset of action can be controlled.
4- Mask the unpleasant/ bitter taste of drug.
5- Can be formulated to provide controlled drug
release, e.g., IM injections
6- May be beneficial for patients having difficulty to
.swallow solid dosage forms
 Disadvantages of Suspension
1- Physical stability, sedimentation and compaction
can causes problems.
2-It is bulky, therefore 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.
5- Agitation is nessessry in suspension .
 Classifications of suspensions
Suspensions can be classified as: 1-
Based to rout of administration: a-
Oral suspension ( ex. Paracetamol suspension) b-
Topical suspension (ex. Calamine Lotion) c-
Parenteral suspension (ex Procaine penicillin G)

Based on behavior of Dispersed Phase: a--2

Flocculated Suspension (Dispersed phase maybe a network of
particle) b-Deflocculated
Suspension (Dispersed phase may consist of discrete particles)
 Ideal properties pharmaceutical
suspensions
Slow settling and readily dispersed when shaken. -1
2-Acceptable odor and color.
3-Gets easily into syringe or flows easily through a
needle (parenteral).
4-It should be physically, chemically and
microbiologically stable during its shelf life.
5-Parenteral/ophthalmic suspension should be
sterilizable.
6-Spreads over surface but doesn’t run off, providing a
.film containing the drug (for lotion application)
 Some theoretic considerations in
suspensions
1) Particle size control.
2) Wettability.
3)Sedimentation.
 Particle size control

• Particle size of any suspension is critical and must be

reduced within the range .

• Too large or too small particles should be avoided.

• Larger particles will: -
settle faster at the bottom of the container
-particles > 5 um impart a gritty texture to the product
and also cause irritation if injected or instilled to the eye.
- particles > 25 um may
block the needle in injections.
• Too fine particles will easily form hard cake at the
bottom of the container.
 Wettability
• It is difficult to disperse solid particles in a liquid
vehicle 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 to remove this air
from the surface and to easy penetration of the
vehicle into the pores.
• Powders, which are not easily wetted by water and
accordingly show a large contact angle, such as sulfur,
charcoal and magnesium stearate are called
hydrophobic.
• Powders which are readily wetted by water are
called hydrophilic e.g. zinc oxide, talc.
• The wettability of a powder may be ascertained
easily by observing the contact angle and
spreading coefficient
 Sedimentation
• Means settling of particle occur under gravitational force
in liquid dosage form.
• Velocity of sedimentation expressed by Stoke’s equation

Where,

Vs= sedimentation velocity in cm / sec

d = Diameter of particle
ρs= density of disperse phase
ρw= density of disperse media
g = acceleration due to gravity
u= viscosity of disperse medium in poise.
• Larger particles will settle faster at the bottom of
the container.
• Thus to slow the sedimentation, particle size
should be reduced by using mortar and pastel.
• But very fine particles will easily form hard cake at
the bottom of the container.
Limitation Of Stoke’s Equation:
• Stoke's equation applies only to:
1-Spherical particles in a very dilute suspension
2-Particles which freely settle without collision .
3-Particles with no physical or chemical attraction
 Interfacial Properties of Suspended
Particles
1- Surface Free Energy:
• The milling (reducing) of the of the particles results in the
increase of the surface area of the particles, hence
increase of the free surface energy which makes the
system thermodynamically unstable.
• In this case the particles is high energetic and tends to
group to reduce the surface area.
• The particles in the liquid suspension therefore tends to
flocculate, and form tight fluffy conglomerates that held
together by weak van der waals forces.
• In some cases these particles may adhere by stronger
forces to form what are termed aggregates (Cake).
2-Adsorption of ions on to the surface of the
particle(surface potential):
• Following immersion solid particles in an aqueous
solution containing electrolytes, ions may be
adsorbed on to the surface of the particle.
• Following adsorption of ions onto the surface, a
phenomenon referred to as the electrical double
layer is established (Nernst potential ,Zeta potential).
 Zeta potential
• Zeta potential is defined as the difference in potential
between the surface of the tightly bound layer and the
electroneutral region of the solution.
• As potential drops off rapidly at first followed more gradual
decrease in as the distance from the surface is increased,
• This is because the counter ions close to the surface acts as
a screen that reduce the electrostatic attraction between
the charged surface and those counter ions further away
from the surface.
• Zeta potential is important in stability of systems containing
dispersed particles,
• Since this potential, rather than the Nernst
potential(surface potential ), governs the degree of
repulsion between the adjacent, similarly charged,
dispersed particles.
• If the Zeta potential reduced below a certain value the
attractive forces exceed the repulsive forces and
particles come together, this phenomenon known as
flocculation.
• Thus the phenomenon of flocculation and
deflocculation depend on zeta potential of the particles.
Zeta potential distance from surface potential
 Flocculation and deflocculation
Flocculated Suspensions:
• Suspension in which particles are weakly bonded,
settle rapidly, do not form a cake and are easily
resuspended with a minimum of agitation.
• In flocculated suspension, formed flocs (loose
aggregates) will cause increase in sedimentation rate
due to increase in size of sedimenting particles.

• Hence, flocculated suspensions sediment more

rapidly.
• Here, the sedimentation depends not only on
the size of the flocs but also
on the porosity of flocs
Deflocculated suspensions:
• Suspension in which particles settle slowly, individual ,and
eventually form a sediment in which aggregation occurs with the
resultant formation of a hard cake which is difficult to resuspended.

• 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 ‘caking’ or ‘claying’.
• In deflocculated suspension larger particles
settle fast and smaller remain in
supernatant liquid so supernatant appears cloudy
Comparison between flocculated system and deflocculated system

Deflocculated suspensions Flocculated suspensions

solids as present as individual Solids form loose aggregate and
particles form network structure
Particles exhibit repulsive forces Particles exhibit attractive forces
Particles
Difficult to resuspended and cake Easy to resuspended
may occur
Particles settle independently Particles settle as flocs
Particles exist as separate entities
Particles exist as loose
aggregates
The supernatant is cloudiness The supernatant is clear
Rate of sedimentation is slow and Rate of sedimentation is high as
size of particle is small flocs are collection of smaller
particles
 Suspensions formulation
The three steps that can be taken to ensure
formulation of an elegant pharmaceutical suspension
are:
1-Control particle size ,On a small scale, this can be
done using a mortar and a pestle to grind down
ingredients to a fine powder.
2- Use thickening agent to increase viscosity of the
vehicle by using suspending agents or viscosity
increasing agents
3- Use of a wetting agents.
1- Drug:
• A water-insoluble drug is usually the dispersed phase in an
aqueous suspension.
• Drugs should be of uniform particle size in the range of 1–
50 μm.
2-Suspending medium or vehicle:
• It may be : 1-
Distilled water or deionized water. 2-
Water- alcohol 3-
Solution of glycerol. 4-
Non-aqueous vehicles (Topical use).
3- Wetting agents:
• The surface of dispersed drug particles can be
hydrophilic or hydrophobic.

• Drugs with hydrophobic surfaces are usually difficult to

disperse in an aqueous medium.

• Wetting agents are surfactants that reduce the surface

tension of an aqueous medium and facilitate the wetting
of hydrophobic particles.
• Wetting agents adsorb onto the particle  surface and can
partially coat the surface or form a complete monolayer. 
Wetting agents may be :
a-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.
• Generally, we use non-ionic surfactants but ionic
surfactants can also be used depending upon certain
conditions.
• Polysorbate 80 is most widely used due to its advantages
which It is non-ionic so no change in pH of medium. and
no toxicity and safe for internal use.
b -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.
• E.g. acacia, tragacanth, alginates, guar gum.
c-Solvents:
• The most commonly used solvents used are alcohol,
glycerin, polyethylene glycol and polypropylene glycol.
• The mechanism by which they provide wetting is that they
are miscible with water and reduce liquid air interfacial
tension.
• Liquid penetrates in individual particle and facilitates
wetting..
4- Suspending agents : (thickener )

These are usually hydrophilic polymers that are added to a suspension

to increase viscosity and retard sedimentation. 
•Most suspending agents have hydrophilic and hydrophobic regions,
and interact with a suspension particle surface. Suspending agents
are often hydrophilic colloids including cellulose derivatives, acacia,
and xanthan gum.
•These suspending agents are added to suspensions to increase
viscosity, inhibit agglomeration, and decrease sedimentation.

•Highly viscous suspensions may prolong gastric emptying time, slow

drug dissolution, and decrease the absorption rate.
5-Flocculating agents :
• Suspended particles that have high charge density usually display
deflocculation and caking upon sedimentation.

• Neutralization of charge of such particles results in flocculation.

• Flocculating agents enable suspended particles to link together in loose

aggregates or flocs through weak bonds.

• These flocs settle rapidly but form large fluffy sediment which is easily
redispersed 
• Examples of flocculating agents are: 1-Neutral
electrolytes such as KCl, NaCl. 2-Surfactants
3-Polymeric flocculating agents : ex.Starch,
alginates, cellulose derivatives, tragacanth.
6-Humectants:
• Humectants absorb moisture and prevent degradation of
API by moisture.
• Examples of humectants most commonly used in
suspensions are propylene glycol ,glycerol.
• Total quantity of humectants should be between 0-10 %
w/w.
7-Sweeteners,
8-Flavors.
9-Colorants.
10-Preservatives
11-Antioxidants
12-Buffers
 preparation of suspensions
Small scale preparation of suspensions:
Step 1:
• Suspensions are prepared by grinding the
insoluble materials in the mortar to a smooth
paste with a vehicle containing the wetting
agent.
Step 2:
• All soluble ingredients are dissolved in same
portion of the vehicle than added to the smooth
paste to step1 to get slurry.
Step 3:
• The slurry is transformed to a graduated cylinder, the mortar is
rinsed with successive portion of the vehicle
Step 4:
• Decide whether the solids are:
-deflacculted
-Flocculated
-Flocculated and then suspended Add
the vehicle containing the suspending agent (or) flocculating
agent
Step5:
• Make up the dispersion to the final volume . Thus
suspension is prepared.
 Evaluation of suspensions (Q.C)
1- Sedimentation Parameters
a-Sedimentation volume :
Sedimentation volume is a ratio of the ultimate
volume of sediment (Vu) to the original volume of
sediment (VO)
before settling.
F = V u / VO
Vu = final or ultimate volume of sediment
VO = original volume of suspension before settling
F has values ranging from less than one to greater
than one.
When F < 1
When F =1
The system is in flocculated equilibrium and show no
clear supernatant on standing.
When F > 1
Sediment volume is greater than the original volume
due to the network of flocs formed in the suspension
and so loose and fluffy sediment
Fig : Suspensions quantified by sedimentation volume (f)
b-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
-The minimum value of ß is 1,when flocculated suspension
sedimentation volume is equal to the sedimentation volume of
deflocculated suspension.
2- Micromeritic method :
• The stability of suspension depends on the particle
size of the dispersed phase
• Change in the particle size with reference to time
will provide useful information regarding the
stability of a suspension.
• A change in particle size distribution and crystal
habit studied by
-microscopy
- coulter counter method
- Photomicroscopic technique:
• The microscope can be used estimate and detect
changes in particle size distribution and crystal form.
• Rapid processing of photo micrographs is enhanced by
attaching Polaroid camera to the piece of
monomolecular
microscope
• By using this photo micrographs we
can determine the changes in
physical properties and stability of
suspensions.
3-Freeze-Thaw test
• Freeze-Thaw test conducted by placing the
sample in a freezer for 18 hours followed by
thawing at room temperature for 4 to 6 hours.
• Repeat the Freeze-Thaw cycle for up to 10
times.
• This test is conducted to determine the
tendency to crystallize or cloud
4- pH measurement
5-Visual inspection