B Pharm 1st semester.

1. SUSPENSIONS
Suspensions are class of liquid dosage forms in which
finely divided solid particles(internal phase) are
dispersed uniformly in a liquid dispersion
medium(external phase). Internal phase particles having
size range from 0.5 microns to 5 microns.
Applications of pharmaceutical suspensions:
1.Drugs which are insoluble . Eg- prednisolone.
2.To enhance the stability of drug. Eg- oxytetracycline
suspension.
3.To control rate of drug absorption. Eg- procaine penicillin.
4.To mask the bitter or unpleasant taste of drug. Eg-
chloramphenicol palmitate suspension.
5.Drug can be formulated for topical application. Eg-
calamine lotion.

2. Suspensions are administered by various routes
1.Oral (eg- antacid suspension)
2.Ocular- through eyes (Eg: Nepafenac ocular
suspension)
3.Otic- through ear (Eg: Cortisporin otic suspension)
4.Rectal-through rectum (mesalamine suspension)
5.Parenteral (eg- procaine penicillin)
6.Topical (eg- calamine lotion)
Examples of Pharmaceutical Suspensions:
1. Antacid oral suspensions
2. Antibacterial oral suspension
3. Dry powders for oral suspension (antibiotic)
4. Analgesic oral suspension
5. Anthelmentic oral suspension
6. Anticonvulsant oral suspension

3. However, there are disadvantages with these formulations
1.Should be shaken prior to use.
2.Uniform and accurate dose cannot be achieved unless
packed in single dosage form.
3.Physical stability, sedimentation can cause problems.
4.Bulky-care should be taken while handling and transport.
5.Formulation of ideal suspension is difficult.
FACTORS TO BE CONSIDERED IN FORMULATION OF
SUSPENSION:
1)Nature of suspended material: The suspended particles
should possess low interfacial tension so that they are easily
wetted by water and hence can be suspended easily. Particles
with high interfacial tension are wetted with the help of
suspending agents( acacia, tragacanth,etc).

4. Factors cont.
 2) Size of suspended particles: As per the
Stroke’s law, the sedimentation rate
decreases when the particle size is
reduced . It is given by the equation:

5. DESIRABLE PROPERTIES of an IDEAL SUSPENSION
1.Particles do not settle rapidly
2.If sedimentation forms - should not form hard cake
3.Sedimentation if occurs should be able to redisperse easily
4.Viscosity should be optimum
5.Easily injectable
6.Should spread easily when applied topically
7.Have acceptable taste
8.Resist microbial attack

6. Classification of Suspensions
 1)Based on route of administration:
 a)Oral suspensions
 b)Parenteral suspensions
 c)Topical suspensions
 2)Based on proportion of solid particles:
 a)Dilute suspension(2 to 10% w/v solid)
 b)Conc. suspension(50% w/v solid)

7. Classification of suspensions
 3)Based on electrokinetic nature of solid
particles:
 a)Flocculated suspension
 b)Deflocculated suspension
 4)Based on size of solid particles:
 a)Colloidal suspension(<1 micron)
 b)Coarse suspension(>1 micron)

8. Deflocculation of particles is obtained when the zeta
potential is higher than the critical value and the repulsive
forces supersede the attractive forces.
When this zeta potential goes below the critical value, the
attractive forces supersede the repulsive forces and
flocculation occurs.
flock
cake

9. DEFLOCCULATED
SUSPENSIONS
FLOCCULATED
SUSPENSIONS
Pleasant appearance Not so
Supernatant cloudy Supernatant clear
Repulsive forces in particles Attractive forces
Particles are separate entity Particles are lose aggregates
Rate of sedimentation is slow Rate is high because of flocs
Particles settle independently Particles settle as flocs
Sediment forms hard cake Sediment forms loosely packed cake
Hard cake cannot be redispersed,
Compact, difficult to redisperse
Sediment easy to redisperse, Porous, easy
to redisperse
Bioavailability is high Bioavailablity is comparatively low

10. PHYSICAL STABILITY OF SUSPENIONS
Pharmaceutical suspensions are thermodynamically stable
systems.
Aggregation of suspended particles and sedimentation
present real problems to the pharmaceutical formulator.
The physical stability is defined as the condition in which
the particles remain uniformly distributed throughout the
dispersion without any signs of sedimentation.
Suspensions are evaluated by determining their physical
stability.

11. Tests for Evaluation of Physical Stability of suspensions
Aesthetic appeal (appearance, color, odor, taste)
pH
Specific gravity
Sedimentation rate
Sedimentation volume
Zeta potential measurement
Compatibility with container
Compatibility with cap-liner
Microscopic examination (photomicrographs)
Determine crystal size
Determine uniform drug distribution

12. Active Tests for Evaluation of Physical Stability of
Suspensions
Redispersibility
Centrifuge
Rheological measurements
Stress tests (vibration to simulate transportation)
Accelerated shock cycles
Freeze-thaw cycles
Use tests
Two useful parameters for the evaluation of
suspensions are
sedimentation volume and
degree of flocculation.

13. Sedimentation volume, F, of a suspension is expressed by
the ratio of the equilibrium volume of the sediment, Vsed
[Vu] to the total volume, Vtot [Vo] of the suspension.
Thus, F = Vsed/Vtot = [Vu] / [Vo]
The value of F provides a qualitative knowledge
about the physical stability of the suspension.
Also used as one of the quality control tool- it is
simple to estimate
Higher the F, more stable the suspension is.

14. The value of F normally lies between 0 to 1 for
any pharmaceutical suspension.
F=0.5 F=1.0 F=1.5
•Vo
•Vu
•Vo
•Vu

16. Degree of flocculation- ß,
is the ratio of the sedimentation volume of the
flocculated suspension, Ffloc, to the sedimentation
volume of the deflocculated suspension, Fdefloc.
Thus,
ß = Ffloc/Fdefloc
=
When the total volume of both the flocculated and
the deflocculated suspensions are same, the
degree of flocculation,
ß = (Vsed)floc /(Vsed)defloc
)defloc
(Vsed/Vtot
)floc
(Vsed/Vtot

17. The minimum value of ß is 1; this is the case when
the sedimentation volume of the flocculated
suspension is equal to the sedimentation volume of
deflocculated suspension.
Degree of flocculation provide quantitative
knowledge of a suspension
Redispersibility
....for practicalsfor 2nd cycle exptsusp2.avi

18. FORMULATION OF SUSPENSIONS
component of suspending system
wetting agent
dispersants
flocculating agent
thickeners
component of the suspending agent
pH control agent
osmotic agent
coloring agents
preservatives to control microbial growth
liquid vehicles

19. METHODS OF PREPARATION
Aim is to prepare physically stable suspensions [desired one
is deflocculated or flocculated]. Hence the normal ways of
doing so are
(1) use of structured vehicle – for deflocculated suspension
(2) use of controlled flocculation – for flocculated suspension
- using electrolytes
- using surfactants
- using polymers
and
(3) Controlled flocculation – structured vehicle

21. Dispersion of solids
 Critical and difficult due to hydrophobicity of
solids
 In addition adsorbed gas prevents and makes
them to float
 Wetting of particles is the first step before
dispersing and this depends on contact angle
θ = 0o : complete wetting
< 90o : partial wetting
> 90o : nonwetting

22. Wetting of solid
(a) Wetting (b) Nonwetting

24. Structured vehicle – Deflocculated suspension
Structured vehicles are the aqueous solutions of natural and
synthetic gums. – act by entrapping the particles [generally
deflocculated particles]
MC, CMC, sodium CMC, acacia, and tragacanth are the
most commonly used structured vehicle in the
pharmaceutical suspensions. [suspensions will be plastic
and pseudo plastic]
Suspensions of higher solids content are prepared
(e.g. toothpaste) using a combination of a clay and
a gum (e.g. NaCMC)
Hydrocolloids are also used as they hydrate well with water
and swell increasing viscosity.
Eg., Nonionic -- MC, HPMC
Ionic -- Sodium CMC, Cabopol
Clays -- Bentonite

25. Structured vehicle – Deflocculated suspension
Hence, these structured vehicles act as suspending
agents
and the concentration depends on
- Viscosity of vehicle – influence stability
- Amount of solids – adding clays calls for use of
preservatives [methyl and propyl parabens]
- Particle size
- Density of solids – density of structured vehicles
increased by including PVPs, PEGs,
sugars, Glycerine

26. Controlled flocculation – using electrolytes
Is obtained by adding flocculating agents which reduces the
zeta potential of the solid particles.
Most frequently used flocculating agents are electrolytes.

27. Controlled Flocculation
Zeta-potential
F=Vu/Vo
Caking Caking
Non-caking
Flocculating Agent
+
+
-
Flocculating agent
changes zeta-potential
of the particles (it can be
electrolyte, charged
surfactant or charged
polymer adsorbing on a
surface).
If the absolute value of
the zeta-potential is too
high the system
deflocculates because of
increased repulsion and
the dispersion cakes.
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.

28. Distanc
e
Energy
Attraction
Repulsion
Attraction
No flocks can form

29. Controlled flocculation – using surfactants
These initiate flocculation by using combination of
ionic and nonionic surface active agents
– reduce interfacial tension,
- act as wetting and
- flocculating agent.
-Concentration is important
-Ionic surfactants – head portion adsorb on solid
tail portion project outward forming bridge
- Nonionic surfactants – form network like structure
between particles

30. Controlled flocculation – using polymers
By using lyophilic polymers. These polymers
form a bridge between particles and initiate
flocculation

31. Controlled flocculation – structured vehicle

32. Thixotropic suspension-A thixotropic suspension is
the one which is viscous during storage but loses
consistency and become fluid upon shaking.
A well-formulated thixotropic suspension would remain
fluid long enough for the easy dispense of a dose but
would slowly regain its original viscosity within a short
time.
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 and excessive heat & light
3) Label: "Shake Before Use" to ensure uniform
distribution of solid particles and thereby uniform and
proper dosage.