PHARMACEUTICAL SUSPENSIONS

 A Pharmaceutical suspension is a coarse dispersion in which

internal phase (therapeutically active ingredient)is dispersed
uniformly throughout the external phase.
 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 ).
 Each phase can exist in solid, liquid, or gaseous state .
 Suspensions are heterogenous system consisting of 2 phases.
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.
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.

Examples of Some Pharmaceutical Suspensions:

1. Antacid oral suspensions
2. Antibacterial oral suspension
3. Dry powders for oral suspension (antibiotic)
4. Analgesic oral suspension
5. Antihelmentic oral suspension
6. Anticonvulsant oral suspension
7. Antifungal oral suspension 2
Applications
 Suspension is usually applicable for drug which is insoluble
(or ) poorly soluble. E.g. Prednisolone suspension
 To prevent degradation of drug or to improve stability of
drug. E.g. Oxy tetracycline suspension
 To mask the taste of bitter of unpleasant drug.
E.g. Chloramphenicol palmitate suspension
 Suspension of drug can be formulated for topical application
e.g. Calamine lotion
 Suspension can be formulated for parentral application in order
to control rate of drug absorption. E.g. penicillin procaine
 Vaccines as a immunizing agent are often formulated as
suspension. E.g. Cholera vaccine
 X-ray contrast agent are also formulated as suspension .
eg: Barium sulphate for examination of alimentary tract.
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 Desired Features 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 must be composed of small uniform sized particles that do not
settle down rapidly.
 It should have pleasing odour, colour and palatability.
 Good syringeability.
 It should be physically, chemically and microbiologically
stable.
 Parenteral /Ophthalmic suspension should be sterilizable.
 Ophthalmic suspension should be formulated in such a way that
the particle size do not exceed 10 micron because below this
size feels comfort and above this size causes pain, irritation and
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 THEORITIC CONSIDERATION OF SUSPENSIONS
 Particle size control.
 Wetting
 Sedimentation
 Brownian movement

Particle size control: Electokinetic

- Particle size of any suspension is critical and must be reduced
within the range .  Aggregation
- 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
Too fine particles will easily form hard cake at the bottom of the
container. 5
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.
THEORY OF SEDIMENTATION
SEDIMENTATION:

Sedimentation means settling of particle (or) floccules occur

under gravitational force in liquid dosage form. 6
 SEDIMENTATION:

Sedimentation means settling of particle (or) floccules occur

under gravitational force in liquid dosage form.
Velocity of sedimentation expressed by Stoke’s

Where,
d = Diameterof particle
r = radius of particle
vsed.= sedimentation velocity in cm / sec
ρ s= density of disperse phase
ρ o= density of disperse media
g = acceleration due to gravity
η o = 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 2gm per
100ml)
 Particles which freely settle without collision .
 Particles with no physical or chemical attraction.
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 = V u / VO
Where,
Vu = final or ultimate volume of sediment
VO = original volume of suspension before settling 8
.

2.Brownian Movement (Drunken walk)

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

Brownian
that movement
their size is below can be observed,
critical radius (r).
 If particle size is about 2 to 5mm
 When the density of particle & viscosity of medium are
favorable.

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3.Electro kinetic 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.

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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.
 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
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. 11
 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.
It is applicable only to deflocculated suspensions. E.g. methyl
cellulose, sodium carboxy methyl cellulose, acacia, gelatin and
tragacanth.
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.
 Too high viscosity is not desirable as:
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. SUSPENSIONS 12
.
INGREDIENTS FOR FORMULATION OF SUSPENSIONS
Wetting agents They are added to disperse solids in continuous
liquid phase.
Flocculating agents They are added to floc the drug particles
Thickeners They are added to increase the viscosity of
suspension.
Buffers They are added to stabilize the suspension to a
and pH adjusting desired pH range.
agents
Osmotic agents They are added to adjust osmotic pressure
comparable to biological fluid.
Coloring agents They are added to impart desired color to
suspension and improve elegance.
Preservatives They are added to prevent microbial growth.

External They are added to construct structure of the final

liquid vehicle suspension. 13
 Suspending agents
Suspending agent are also known as hydrophilic colloids which form
colloidal dispersion with Water and increase the viscosity of the
continous phase.
List of Suspending Agents
Alginates
•Methylcellulose
•Hydroxyethylcellulose
•Carboxymethylcellulose
•Sodium Carboxymethylcellulose
•Microcrystalline cellulose
•Acacia
•Tragacanth
•Xantham gum
•Bentonite
•Carbomer
•Carrageen
•Powdered cellulose
•Gelatin 14
 Wetting Agents
 Hydrophilic materials are easily wetted by water while hydrophobic
materials are not.
 However hydrophobic materials are easily wetted by non-polar
liquid.
 The extent of wetting by water is dependent on the hydrophillicity of
the materials.
 If the material is more hydrophilic less difficulty in wetting by water.
 The concentration used isSurfactants
less than 0.5 %.
 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 following advantages
 It is non-ionic so no change in pH of medium
 No toxicity. Safe for internal use.
SUSPENSIONS 15
 Hydrophilic Colloids
 Hydrophilic colloids coat hydrophobic drug particle in one or
more than one layer.
 This will provide hydrophillicity to drug particles and facilitate
wetting.
 They cause deflocculation of suspension because force of
attraction is declined. e.g. acacia, tragacanth, alginates, guar
gum.
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.
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n.

Buffers
Buffers are the materials which when dissolved in a
solvent will resist any change in pH when an acid or base is
added.
 To encounter stability problems all liquid formulation should be
formulated to an optimum pH.
 Rheology, viscosity and other property are also dependent on
the pH of the system.
Generally pH of suspension preferably at 7.4-8.4.
 Most commonly used buffers are salts of weak acids such as
carbonates, citrates, gluconates, phosphate and tartrates.
Osmotic Agents
They are added to produce osmotic pressure comparable to
biological fluids when suspension is to be intended for
ophthalmic or injectable preparation.
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 Most commonly used osmotic agents are: dextrose, mannitol,
sorbitol, sodium chloride, sodium sulfate, glycerol.
Preservatives
Naturally occurring suspending agents such as tragacanth, acacia,
xanthan gum are susceptible to microbial contamination.
This leads to:
 loss in suspending activity of suspending agents,
 loss of color, flavor and odor,
 change in elegance etc.

Name of preservatives
Propylene glycol
Disodium EDTA
Benzalkonium chloride
Benzoic acid
Butyl paraben 18
 Flavoring And Coloring Agents
 They are added to increase patient acceptance.
 Only sweetening agent are not capable of complete taste
masking of unpleasant drugs therefore, a flavoring agents are
incorporated.
Acacia Ginger Sarsaparilla
syrup
Anise oil Glucose Spearmint oil
Benzaldehyde Glycerin Thyme oil

Coloring agents
 Colors are obtained from natural or synthetic sources.
Plant colors are most widely used for oral suspension.
 The synthetic dyes should be used within range of( 0.0005 %
to 0.001%) 19
 Color aids in identification of the product.
 The color used should be acceptable by the particular country.
Most widely used colors are as following:ium dio
Brilliant blue (blue)
Indigo carmine(blue)
Amaranth (red)
Tartarazine (yellow)
Annatto seeds(yellow to orange)

Sweetening Agents
They are used for taste masking of bitter drug particles.
Bulk sweeteners
 Sugars such as 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 20
 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.
Antioxidant
 Ascorbic acid derivatives such as ascorbic acid, erythorbic
acid,
Thiol derivatives such as thio glycerol, cytosine, acetylcysteine,

 Tocopherols
 Butylated hydroxy anisole(BHA)
 Butylated hydroxytoluene (BHT)
Sodium bi sulfite, 21


 PREPARATION OF SUSPENSIONS

Following consideration are important for manufacturing

pharmacist
 Selection of right material that go into the manufacture.
 The step involved and their sequence in the manufacture.
 Preservation and storage of the product.
Small scale preparation of suspensions:
Step 1:
Suspensions are prepared by grinding (or) levigating 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 and added to the smooth paste to step1 to get slurry.
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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
Suspended in a structured vehicle
Flocculated
Flocculated and then suspended
Add the vehicle containing the suspending agent (or)
flocculating agent
Step-5:
Make up the dispersion to the final volume . Thus suspension is
prepared.

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 Evaluation of Suspensions
Sedimentation method
Rheological method
 Electro kinetic method
 Micromeritic method
Sedimentation method :
Two parameters are studied for determination of sedimentation.
1. Sedimentation volume,
2. Degree of flocculation.
Sedimentation volume
The suspension formulation (50 mL) was poured separately into
100 mL measuring cylinders and sedimentation volume was read
after 1, 2, 3 and 7 days, and thereafter at weekly intervals for 12 weeks.
 Triplicate results were obtained for each formulation.
Sedimentation volume was calculated according to the equation:
F = Vu/Vo
Where, F = sedimentation volume, Vu = ultimate height of sediment
24
and Vo = initial height of total suspension
Rheological method
 It provide information about Settling behaviour .
The arrangement of the vehicle and the particle structural
features.
 Brookfield viscometer is used to study the viscosity of the
suspension .
 It is mounted on heli path stand and using T-bar spindle.
T-bar spindle is made to descend slowly into the suspension and
the dial reading on the viscometer is then a measure of the
resistance the spindle meets at various level.
This technique also indicates at which level of the suspension
the structure is greater owing to particle agglomeration.
 The dial reading is plotted against the number of turns of the
spindle.
 The better suspension show a lesser rate of increase of dial
reading with spindle turns, i.e. the curve is horizontal for long
period. 25
Electro kinetic method
 Measurement of Zeta-potential using Micro electrophoresis
apparatus & ZetaPlus (Brookhaven Instruments Corporation,
USA).
It shows the stability of a disperse system.
Zeta potential
The zeta potential of the formulated suspensions was
determinedusing a ZetaPlus (Brookhaven Instruments,
Corporation,USA).
Approximately 1 mL of suspension was transferred into a
plastic cuvette using a pipette and diluted with distilled water.
 The Brookhaven zeta potential software was used for the
measurement .
Parameters set to a temperature of 250C and refractive index
The zeta potential of the formulations was determined on day
0, 7, 14, 21 and day 28 post formulation. 26
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.
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)

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