UNIT IV

SUSPENSIONS

Momena Akter
Lecturer
Department of pharmacy
SRM COLLEGE OF PHARMAY
 CONTENTS
¾Definition.

¾Classification.

¾Advantages & disadvantages.

¾Applications.
¾Theoretic consideration of suspensions.
•Sedimentation
•Brownian movement
•Electrokinetic properties
¾Formulation of suspensions

¾Packing of suspensions

¾Storage requirement & labelling

¾Evaluation of suspension

¾Dissolution study of suspensions

¾Innovation of suspensions
 DISPERSE SYSTEM

y 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 ).

y Each phase can exist in solid, liquid, or gaseous state .

y Suspensions are heterogenous system consisting of 2

phases.
A solid in liquid dispersion in which the particles are
of colloidal size.

DISPERSE SYSTEM

DISPERSED MEDIUM DISPERSED PHASE

oAqueous oily liquid oInsoluble solid

 Definition

¾ A Pharmaceutical suspension is a coarse dispersion in which internal

phase (therapeutically active ingredient)is dispersed uniformly
throughout the external phase.
¾ 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.

¾ 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.

 SOME MARKETED
SOME PHARMACEUTICAL SUSPENSIONS
SUSPENSIONS

y 1. Antacid oral suspensions

y 2. Antibacterial oral suspension
y 3. Dry powders for oral suspension (antibiotic)
y 4. Analgesic oral suspension
y 5. Anthelmentic oral suspension
y 6. Anticonvulsant oral suspension
y 7. Antifungal oral suspension
Classification
Based On General Classes
¾ Oral suspension
eg: Paracetamol suspension
antacids, Tetracycline HCl.

¾ Externally applied suspension

eg :Calamine lotion.

¾ Parenteral suspension
eg: Procaine penicillin G
Insulin Zinc Suspension
Based on Proportion of Solid Particles
¾ Dilute suspension (2 to10%w/v solid)

Eg: cortisone acetate, predinisolone acetate

¾ Concentrated suspension (50%w/v solid)

Eg: zinc oxide suspension

Based on Electrokinetic Nature of Solid Particles

¾ Flocculated suspension

¾ Deflocculated suspension
Based on Size of Solid Particles

¾Colloidal suspensions (< 1 micron)

-Suspensions having particle sizes of suspended solid less than

about 1micron in size are called as colloidal suspensions.
Coarse suspensions (>1 micron)
¾Suspensions having particle sizes of greater than about
1micron in diameter are called as coarse suspensions.

Coarse dispersion
Barium sulphate

Nano suspensions (10 ng)

¾ Suspensions are the biphasic colloidal dispersions of

nanosized drug particles stabilized by surfactants.
¾Size of the drug particles is less than 1mm.
Advantages And Disadvantages
Advantages
.Suspension can improve chemical stability of certain drug.
E.g. Procaine penicillin G.

¾Drug in suspension exhibits higher rate of bioavailability than other

dosage forms.

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

¾Duration and onset of action can be controlled.

E.g. Protamine Zinc-Insulin suspension.

¾Suspension can mask the unpleasant/ bitter taste of drug.

E.g. Chloramphenicol
 Disadvantages

¾ Physical stability , sedimentation and compaction can causes

problems.

¾ It is bulky sufficient care must be taken during handling and

transport.

¾ It is difficult to formulate.

¾ Uniform and accurate dose can not be achieved unless

suspension are packed in unit dosage form.
Applications

¾ Suspension is usually applicable for drug which is insoluble

(or ) poorly soluble.
E.g. Prednisolone suspension

¾ To prevent degradation of drug or to improve stability of

drug.
E.g. Oxy tetracycline suspension

¾ To mask the taste of bitter of unpleasant drug.

E.g. Chloramphenicol palmitate suspension

¾ Suspension of drug can be formulated for topical application

e.g. Calamine lotion
¾ Suspension can be formulated for parentral application in order to
control rate of drug absorption. E.g. penicillin procaine

¾ Vaccines as a immunizing agent are often formulated as suspension.

E.g. Cholera vaccine

¾ X-ray contrast agent are also formulated as suspension .

eg: Barium sulphate for examination of alimentary tract.
 Features Desired In Pharmaceutical Suspensions
¾ The suspended particles should not settle rapidly and sediment
produced, must be easily re-suspended by the use of moderate
amount of shaking.

¾ It should be easy to pour yet not watery and no grittiness.

¾ It should have pleasing odour , colour and palatability.

¾ Good syringeability.

¾ It should be physically,chemically and microbiologically stable.

¾ Parenteral /Ophthalmic suspension should be sterilizable.

THEORITIC CONSIDERATION OF SUSPENSIONS

A knowledge of the theoretic considerations pertaining to

suspension s technology ultimately help formulator to select
ingredients that are

ƒAppropriate for suspension preparation

ƒThat available for milling

ƒMixing equipment
ƒSome theoretic considerations are :

ƒParticle size control.

ƒWetting

ƒSedimentation

ƒ Brownian movement

ƒElectokinetic

ƒAggregation
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:
¾ settle faster at the bottom of the container
¾ particles > 5 um impart a gritty texture to the product
and also cause irritation if injected or instilled to the eye
¾ particles > 25 um may block the needle

-Too fine particles will easily form hard cake at the bottom
of the container.
Wetting of the particles
y 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.

y Thus, the particles, even high density, float on the surface of the
liquid until the layer of air is displaced completely.

y The use of wetting agent allows removing this air from

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

y 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.

2.1.

Velocity of sedimentation expressed by Stoke’s equation

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
Limitation Of Stoke’s Equation .

Stoke's equation applies only to:

¾ Spherical particles in a very dilute suspension (0.5 to 2 gm per

100 ml)

¾ Particles which freely settle without collision .

¾ 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
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
The sedimentation volume gives only a qualitative account of
flocculation.

Fig : Suspensions quantified by sedimentation volume (f)

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
¾The minimum value of ß is 1,when flocculated suspension
sedimentation volume is equal to the sedimentation volume
of deflocculated suspension.
.

2.Brownian Movement (Drunken walk)

¾ Brownian movement of particle prevents sedimentation

by keeping the dispersed material in random motion.

¾ Brownian movement depends on the density of dispersed

phase and the density and viscosity of the disperse medium.

¾ 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).
¾ Brownian movement can be observed,

¾ If particle size is about 2 to 5mm,

¾ When the density of particle & viscosity of medium are

favorable.
Brownian motion is given by equation:

Where, R = gas constant

T = temp. in degree Kelvin
N = Avogadro’s number
η = viscosity of medium
t = time
r = radius of the particle
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.
¾ As the potential drops off rapidly
b at first, followed more gradual
decrease as the distance from the surface increases.

¾ 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.
¾ Zeta potential has practical application in stability of systems
containing dispersed particles .

¾ Since this potential, rather than the Nernst potential, governs the
degree of repulsion between the adjacent, similarly charged,
dispersed particles.

¾ If the zeta potential is reduced below a certain value , the attractive

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

¾ This phenomenon is known as flocculation.

¾ The flocculated suspension is one in which zeta potential of
particle is -20 to +20 mV.

¾ Thus the phenomenon of flocculation and de flocculation

depends on zeta potential carried by particles.
Deflocculation and flocculation
Flocculated Suspensions
¾ In flocculated suspension, formed flocs (loose aggregates) will cause
increase in sedimentation rate due to increase in size of sedimenting
particles.

¾ Hence, flocculated suspensions sediment more rapidly.

¾Here, the sedimentation depends not only on the size of the flocs but
also on the porosity of flocs.
Deflocculated suspensions

¾In deflocculated suspension, individual particles are

settling.

¾ Rate of sedimentation is slow , which prevents

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

¾This phenomenon called ‘caking’ or ‘claying’.

¾ In deflocculated suspension larger particles settle fast

and smaller remain in supernatant liquid so supernatant
appears cloudy.
 :
FORMULATION OF SUSPENSIONS

¾ The formulation of a suspension depends on whether the

suspension is flocculated or deflocculated.

¾ Three approaches are commonly involved

1. Use of structured vehicle

2. Use of controlled flocculation
3. Combination of both of the methods
Flow chart of formulation of suspension
 Structured vehicle

¾ Structured vehicles called also thickening or suspending

agents.

¾ They are aqueous solutions of natural and synthetic gums.

¾These are used to increase the viscosity of the suspension.

¾It is applicable only to deflocculated suspensions.

E.g. methyl cellulose, sodium carboxy methyl cellulose,
acacia, gelatin and tragacanth.
¾These structured vehicles entrapped the particle and
reduces the sedimentation of particles.

¾Thus, the use of deflocculated particles in a structure vehicle

may form solid hard cake upon long storage.
¾Too 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.

¾ Structured vehicle is not useful for Parenteral suspension

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

Controlled flocculation of particles is obtained by

adding flocculating agents, which are:

(1) electrolytes

(2) surfactants

(3) polymers
 Flocculation in structured vehicles

¾ Sometimes suspending agents can be added to

flocculated suspension to retard sedimentation

Examples of these agents are:

ƒCarboxymethylcellulose (CMC),
ƒ Carbopol 934,
ƒVeegum, and bentonite
 INGREDIENTS FOR

FORMULATION OF SUSPENSIONS
.

Wetting agents They are added to disperse solids in continuous

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

Buffers They are added to stabilize the suspension to a

and pH adjusting agents desired pH range.

Osmotic They are added to adjust osmotic pressure

agents comparable to biological fluid.

Coloring They are added to impart desired color to

agents suspension and improve elegance.
Preservatives They are added to prevent microbial growth.

External They are added to construct structure of the

liquid vehicle final suspension.
 Suspending agents

¾ Suspending agent are also known as hydrophilic colloids

which form colloidal dispersion with Water and increase the
viscosity of the continous phase.

¾Suspending agent form film around particle and decrease

interparticle attraction.

¾ Most suspending agents perform two functions

i.e. besides acting as a suspending agent

they also imparts viscosity to the solution.
¾ Preferred suspending agents are those that give thixotropy to the
media such as

Xanthan gum,
Carageenan,
Na CMC/MC mixers,
Avicel RC 591
Avicel RC 581 and
Avicel CL 611.
.
Stability pH range and concentrations of most commonly used suspending agents.
Suspending agents Stability pH Concentrations used as
range suspending
agent

Sodium alginate 4-10 1– 5 %

Methylcellulose 3-11 1– 2 %
Hydroxyethyl cellulose 2-12 1-2%
Hydroxypropyl cellulose 6-8 1-2%
Hydroxypropyl 3-11 1-2%
methylcellulose
CMC 7-9 1-2%

Colloidal 0-7.5 2- 4 %
silicon dioxide
List of Suspending Agents
Alginates
•Methylcellulose
•Hydroxyethylcellulose
•Carboxymethylcellulose
•Sodium Carboxymethylcellulose
•Microcrystalline cellulose
•Acacia
•Tragacanth
•Xantham gum
•Bentonite
•Carbomer
•Carrageen
•Powdered cellulose
•Gelatin
Alginates

¾ Alginate salts have about same suspending action to that

of Tragacanth.

¾ Alginate solution looses its viscosity when heated above 60ºC.

due to polymerization.

Alginate granules
¾ Maximum viscosity is observed at a pH range of 5-9 of
alginate.

¾ Chemically alginates are polymers composed of mannuronic

acid and glucuronic acid monomers.

¾ In practice, alginate is used at concentration less than 10 %

w/w, particularly at 5 % w/w.
 Methylcellulose

¾ Methylcellulose is available in several viscosity grades.

¾ The difference in viscosity is due to difference in methylation

and polymer chain length.

¾ Methylcellulose is more soluble in cold water than hot water.

¾ Methylcellulose is stable at pH range of 3-11.

Methyl cellulose on on Solution form
Gel form
heating cooling

Methyl cellulose
powder
¾Hydroxy ethylcellulose:

¾ Hydroxyethylcellulose (HEC) is another good

suspending agent having somewhat similar characteristics
to methylcellulose.

¾ In HEC hydroxyethyl group is attached to cellulose chain.

¾ Unlike methylcellulose, HEC is soluble in both hot and cold water

and do not form gel on heating.
Carboxy methylcellulose (CMC)

¾ Carboxy methylcellulose is available at different viscosity grades.

¾ Low, medium and high viscosity grades are commercially

available.

¾ In case of HV-CMC, the viscosity significantly decreases when

temperature rises to 40 ºC from 25 ºC.

¾ Therefore, to improve viscosity and stability of suspension MV-CMC

is widely accepted.
Microcrystalline Cellulose (MCC; Tradename-Avicel)

¾ It is not soluble in water, but it readily disperses in water to give

thixotropic gels.

¾ It is used in combination with Na-CMC, MC or HPMC, because

they facilitate dispersion of MCC.
The advantages of MCC:

¾ Alginate complex compositions are that they provide excellent

stability.

¾ Formulation of dry powder suspensions with MCC;

Alginate complexes produce an excellent dry readily hydratable

and dispersible formulation for reconstitution.
 Wetting Agents
¾ Hydrophilic materials are easily wetted by water while hydrophobic
materials are not.

¾ However hydrophobic materials are easily wetted by non-polar

liquids.

¾ The extent of wetting by water is dependent on the hydrophillicity of

the materials.

¾ If the material is more hydrophilic less difficulty in wetting by

water.

¾ The concentration used is less than 0.5 %.

.

Surfactants

¾ 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.

¾ Generally, we use non-ionic surfactants but ionic surfactants can

also be used depending upon certain conditions.

¾Polysorbate 80 is most widely used due to its following advantages

ƒ It is non-ionic so no change in pH of medium

ƒ No toxicity. Safe for internal use.
 Hydrophilic Colloids

¾ Hydrophilic colloids coat hydrophobic drug particles

in one or more than one layer.

¾ This will provide hydrophillicity to drug particles and facilitate

wetting.

¾ They cause deflocculation of suspension because force of

attraction is declined. e.g. acacia, tragacanth, alginates, guar
gum.
 Solvents
¾ The most commonly used solvents used are alcohol,
glycerin, polyethylene glycol and polypropylene glycol.

¾ The mechanism by which they provide wetting is that they

are miscible with water and reduce liquid air interfacial tension.

¾ Liquid penetrates in individual particle and facilitates wetting.

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.

¾ To encounter stability problems all liquid formulation should be

formulated to an optimum pH.

¾ Rheology, viscosity and other property are also dependent on the

pH of the system.
¾. Generally pH of suspension preferably at 7.4-8.4.

¾ Most commonly used buffers are salts of weak acids such as

carbonates,
citrates,
gluconates,
phosphate and tartrates.
 Osmotic Agents
¾ They are added to produce osmotic pressure comparable to
biological fluids when suspension is to be intended for
ophthalmic or injectable preparation.

¾ Most commonly used osmotic agents are

ƒ dextrose,
ƒ mannitol
ƒ sorbitol.
ƒ sodium chloride,
ƒ sodium sulfate
ƒ glycerol.
 Preservatives

¾ Naturally occurring suspending agents such as tragacanth, acacia,

xanthan gum are susceptible to microbial contamination.

¾This leads to:

ƒ loss in suspending activity of suspending agents,

ƒ loss of color, flavor and odor,
ƒ change in elegance etc.
Name of preservatives Concentration 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

Disodium EDTA benzalkanonium

 Flavoring And Coloring Agents

¾ They are added to increase patient acceptance.

¾ Only sweetening agent are not capable of complete taste masking

of unpleasant drugs therefore, a flavoring agents are incorporated.
Eg:

Acacia Ginger Sarsaparilla

syrup
Anise oil Glucose Spearmint oil
Benzaldehyde Glycerin Thyme oil
 Coloring agents

¾ Colors are obtained from natural or synthetic sources.

¾Plant colors are most widely used for oral suspension.

¾ The synthetic dyes should be used within range of( 0.0005 % to

0.001%)

¾ Color aids in identification of the product.

¾ The color used should be acceptable by the

particular country.
Most widely used colors are as follows.

¾· Titanium dioxide (white)

¾· Brilliant blue (blue)

¾· Indigo carmine(blue)

¾· Amaranth (red)

Annatto seeds
¾·Tartarazine (yellow)
¾Annatto seeds(yellow to orange)
 Sweetening Agents
They are used for taste masking of bitter drug particles.

Bulk sweeteners

¾ Sugars such as xylose, ribose, glucose, mannose.

¾ 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
 Humectants
¾ Humectants absorb moisture and prevent degradation of API by
moisture.

¾Examples of humectants most commonly used in

suspensions are

¾ propylene glycol

¾glycerol.

¾Total quantity of humectants should be between 0-10 % w/w.

 Antioxidant
¾Ascorbic acid derivatives such as ascorbic acid, erythorbic acid,

¾Thiol derivatives such as thio glycerol, cytosine, acetylcysteine,

¾ Tocopherols

¾ Butylated hydroxy anisole(BHA)

¾ Butylated hydroxytoluene (BHT)

¾Sodium bi sulfite,

¾Sodium sulfateacetone
 PREPARATION OF SUSPENSIONS

Following consideration are important for manufacturing

pharmacist

ƒ Selection of right material that go into the manufacture.

ƒ The step involved and their sequence in the manufacture.

ƒ 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:
ƒ All soluble ingredients are dissolved in same portion of the
vehicle and 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
¾Suspended in a structured vehicle
¾Flocculated
¾Flocculated 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.

 Packaging of Suspensions

Introduction

¾ Pharmaceutical suspensions for oral use are generally packed

in wide mouth container having adequate space above the
liquid to ensure proper mixing.

¾ Parenteral suspensions are packed in either glass ampoules or

vials.
Ideal Requirements of Packaging Material

¾ It should be inert.

¾ It should effectively preserve the product from light,

air, and other contamination through shelf life.

¾ It should be cheap.

¾ It should effectively deliver the product without any

difficulty.
Materials Used For Packaging

Generally glass and various grades of plastics are used in

packaging of suspension.
Glass

Generally soda lime and borosilicate glass are used

in preparation of non sterile suspensions.
¾ Amber glass doesn’t allow U.V light to pass through.

¾ Amber characteristics can be developed in the

glass by addition of various types of additives.

Type of glass Additive giving amber

color
Soda lime FeO + sulfur (in
presence of reducing
agent)
Borosilicate FeO+TiO 2
Disadvantages of Glass Materials:

¾They are fragile.

¾They are very heavy as compared to plastic so

handling and transport is difficult.

¾ Most important disadvantage of glass that

glass constituents get extracted into the product.
Plastic
Due to the negative aspects of glass, plastic material
significantly use of plastic as packaging material for sterile as
well as non-sterile pharmaceutical suspension increased.
Advantages Of Plastic Material:

•Non breakability.
•Light weight.
•Flexibility.

Materials used: -

Polyethylene, PVC, polystyrene, polycarbonate etc

Closure And Liners

With an exception of ampoules all containers required

elastomeric closure.

closures

liners
Factors affecting in selecting closure:

¾Compatibility with product.

¾ Seal integrity.

¾It should be stable throughout the shelf life.

Factors affecting in selecting liner:

¾ Chemical resistance.
¾ Appearance
¾ Gas and vapor transmission.
¾ Removal torque.
¾ Heat resistance.
¾ Shelf life.
¾ Economical factors
 STORAGE REQUIREMENTS & LABELLING

Labelling:

¾Shake well before use

¾Do not freeze

¾Protect from direct light(for light sensitive drugs)

¾ In case of dry suspensions powder the specified amount of

vehicle to be mixed may indicated clearly on label.
Label:
 STORAGE :

¾ Suspensions should be stored in cool place but should not be kept

in a refrigerator

¾ Freezing at very low temperatures should be avoided which may

lead to aggregation Of suspended particles

0
Stored at controlled temperature from 20-25 c
Evaluation of Suspensions

¾ Sedimentation method

¾ Rheological method

¾ Electro kinetic method

¾ Micromeritic method
Sedimentation method :

Two parameters are studied for determination of sedimentation.

1. Sedimentation volume,

2. Degree of flocculation.
,
Sedimentation volume

¾The 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.

¾ Triplicate results were obtained for each formulation.

¾Sedimentation volume was calculated according to the equation:

F = Vu/Vo
¾Where, F = sedimentation volume, Vu = ultimate height of sediment
and Vo = initial height of total suspension
¾Rheological method

¾ It provide information about Settling behaviour .

¾The arrangement of the vehicle and the particle structural

features.

¾ Brookfield viscometer is used to study the viscosity of the

suspension .
¾ It is mounted on heli path stand and using T-bar spindle.

¾T-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.
¾ This technique also indicates at which level of the suspension
the structure is greater owing to particle agglomeration.

¾ The dial reading is plotted against the number of turns of the

spindle.

¾ The better suspension show a lesser rate of increase of dial

reading with spindle turns, i.e. the curve is horizontal for long
period.
Electro kinetic method

¾ Measurement of Zeta-potential using Micro electrophoresis

apparatus & ZetaPlus (Brookhaven Instruments Corporation, USA)

¾It shows the stability of a disperse system.

Micro-Electrophoresis
Apparatus Mk I

ZetaPlus
Zeta potential

¾The zeta potential of the formulated suspensions was determined

using a ZetaPlus (Brookhaven Instruments Corporation, USA).

¾Approximately 1 mL of suspension was transferred into a plastic

cuvette using a pipette and diluted with distilled water.

¾ The Brookhaven zeta potential software was used for the

measurement .
¾Parameters set to a temperature of 250C and refractive index (1.33)

¾The zeta potential of the formulations was determined on day 0, 7,

14, 21 and day 28 post formulation.
 Micromeritic method :

¾The stability of suspension depends on the particle size of the

dispersed phase.

¾ Change in the particle size with reference to time will provide

useful information regarding the stability of a suspension.

¾A change in particle size distribution and crystal habit studied by

¾ microscopy

¾ coulter counter method

PHOTOMICROSCOPIC TECHNIQUE

¾The microscope can be used estimate and detect changes in

particle size distribution and crystal form.

¾Rapid processing of photo micrographs is enhanced by attaching

Polaroid camera to the piece of monomolecular microscope

¾By using this photo micrographs we can

determine the changes in physical properties
and stability of suspensions.
 FREEZE- THAW TEST
¾ 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.

¾Repeat the Freeze-Thaw cycle for up to 10 times.

¾This test is conducted to determine the tendency to crystallize or cloud

Freeze-thaw testing freezer INNER CHAMBER

 pH MEASUREMENT

¾ The measurement and maintenance pH is also very important step in

the Quality control testing .

¾ Generally there are 2 different types of methods used in the

measurement of pH.
METHODS FOR pH MEASUREMENT:

¾ The simplest and cheapest is to dip a piece of pH paper into the

sample.

¾ The paper is impregnated with chemicals that change color and the
color may be compared to a chart supplied with the paper to give
the pH of the sample.
¾ If greater accuracy is required a pH meter should be
used.

¾ A typical pH meter consists of a special measuring glass

electrode connected to an electronic meter that measures and
displays the pH reading.
VISUAL INSPECTION:

¾ With visual inspection, the ingredients and the final

products are carefully examined for purity and for
appearance .

¾ Physical appearance of products for patient adherence

and compliance is critical so it should be:
Good looking
Elegance in appearance .
 DISSOLUTION STUDY OF SUSPENSIONS

Introduction:

The drug release from suspensions is mainly through dissolution.

¾ Suspensions share many physico-chemical characteristics of

tablet & capsules with respect to the process of dissolution.

¾ As tablets & capsules disintegrate into powder and form

suspensions in the biological fluids.

¾ So dissolution is carried as follows

Dissolution Testing

Official Method (Conventional Method):

¾ It is known as paddle method.

¾The apparatus consists of a cylindrical 1000- ml round bottom
flask in a multiple – spindle dissolution drive apparatus and
immersed in a controlled temp bath maintained

¾Dissolution profile of the 500 mg sample suspension is

¾ determined at 37°C in 900 ml of

¾ pH 7.2 phosphate buffer using

¾ the FDA paddle method at 25 RPM.

¾ The paddle should position to extend to exactly 2.5 cm
above the flask bottom.

¾ The suspension is to be introduced carefully into the

flask at the bottom using a 10- ml glass syringe with an
attachment 19-cm needle.

¾ Withdraw 5 ml of dissolution medium (and replace

with an equal volume of drug –free buffer) in a 5 ml glass
syringe.

¾ Immediately filter through a 0.2 µm membrane and

analyze.
INNOVATIONS OF SUSPENSIONS

1. Nano suspensions

2. Taste masked pharmaceutical suspensions

3. Sustained release suspensions

 1. Nano suspensions:

¾ Nano suspensions are the biphasic colloidal dispersions

of nano sized drug particles stabilised by surfactants
without the matrix materials.

¾They can also be defined as a biphasic system consisting of

pure drug particles dispersed in an aqueous vehicle in which
the diameter of the suspended particle is less than 1 μm in
size.
 2.Taste Masked Pharmaceutical
Suspensions .

¾ Un-palatability due to bad taste is a major concern

in most of the dosage forms containing bitter drugs.

¾ In case of suspensions also taste masking is being applied to

mask bitterness of drugs formulated.
The taste masking approaches for suspensions are:

a. Polymer coating of drugs.

b. Encapsulation with basic drugs.

c. Polymer coating with basic substances.

d. Coating and pH control.

a. Polymer Coating of Drugs

The polymer coat allows the time for all of the particles to be
swallowed before the threshold concentration is reached in the
mouth and the taste is perceived.

The polymers used for coating are

•Ethyl cellulose
•Eudragit RS 100
•Eudragit RL 100
•Eudragit RS 30 D
•Eudragit RL 30 D
b. Encapsulation with a Basic Substance

¾Here a basic substance is mixed with a bitter tasting drug which is

insoluble at high pH.

¾The mixer is then encapsulated with a polymer (cellulose

derivative, vinyl derivative or an acid soluble polymer
Eg: copolymer of dimethyl ammonium methyl methacrylate).

¾The drug after encapsulation are suspended, dispersed or

emulsified in suspending medium to give the final dosage form.
c. Coating and pH Control

¾Those drugs which are soluble at high pH are preferably be

maintained in a suspension at a low pH where the drug exhibit
maximum insolubility.

¾ Similarly drugs which are soluble at low pH are preferably

maintained in suspension at a high pH where the drug is insoluble.

¾Also applying polymeric coating to the drug substance avoids

solubilization of drug when administered providing taste masking.
 Some Examples of Taste Masked Suspensions
Sr.No Name of the drug Taste masking approach

1 RISPERIDONE pH
control and polymer coating
(with Eudragit RS)

2 DICLOFENAC Polymer
coating with Eudragit RS
100

3 LEVOFLOXACIN Polymer
coating (Eudragit
&cellulose acetate,)
 Sustained Release Suspensions

¾ Sustained release is a method to increase only the duration of

action of drug being formulated without affecting onset of
action.

¾ In suspension sustained release affected by coating the drug to be

formulated as suspension by insoluble polymer coating.

¾ The polymer coating provides sustained release and also masks

the taste of the bitter drug.
¾ The polymer used for sustained release in suspension is
as follows as
¾ Ethyl cellulose,
¾Eudragit,
¾Cellulose acetate, etc.

¾ The main advantage of sustained release

suspension is decrease in dosing frequency.
Approaches used in formulation of sustained release oral suspensions

1. Ion exchange resin.

2. Microencapsulation technique

3. Saturated drug suspension as a suspending medium.

4. Using non aqueous vehicle.

5. Reconstitution.

6. Protective coating.
 REFERENCES
¾ Subramanyam C.V.S., Second edition, “Suspensions” Text
Book of Physical Pharamaceutics, PageNo. 374-387.

¾ Ansel C., Allen L.V., Popovich N.G. Eighth edition

“Disperse systems” Pharmaceutical Dosage Forms & Drug
Delivery Systems, Lippincott Williams and Wilkins,
Philadelphia 2005, Page No. Page No. 387-389, 398.
¾ Cooper & Gun, Sixth edition, “Dispersed system” Tutorial
Pharmacy, Page No. 75-78.

¾ Aulton M.E. Second edition, “Suspension” Pharmaceutics-

The Science of Dosage Form Design, Churchill Livingstone,
Edinburgh 2002, PageNo. 84-86, 273.
¾ Martin A. Fourth edition, “Coarse dispersion”
Physical Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2001, Page No. 479-481.

¾ Remington, Twentieth edition, “Colloidal

Dispersions” The Science and Practice of
Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2000, Page No. 298-307.
 Heartly thanks to
Prof .Dr. M.B.Venkatapathi Raju Sir,Principal,SRCP.
Prof : G.Sudhakar sir , Vice principal,SRCP.
Prof .Dr. R. Santosh Kumar sir , H.O.D,SRCP.

My Teachers and other faculty members and

non teaching staff,SRCP.

Finally special thanks to Srinivasa Rao College of

Pharmacy Management.