SUSPENSIONS

DEPARTMENT OF PHARMACEUTICS

CHALAPATHI INSTITUE OF PHARMACEUTICAL

SCIENCES
 CONTENTS
Definition.

Classification.

Advantages & disadvantages.

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

2
Formulation of suspensions

Packing of suspensions

Storage requirement & labelling

Evaluation of suspension

Dissolution study of suspensions

Innovation of suspensions

3
 DISPERSE SYSTEM
4

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.

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

DISPERSE SYSTEM

DISPERSED MEDIUM DISPERSED PHASE

oAqueous oily liquid oInsoluble solid

5
 Definition
6
 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
7 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.
 8
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

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
7. Antifungal oral suspension
Classification
Based On General Classes
 Oral suspension
eg: Paracetamol suspension
antacids, Tetracycline HCl.

 Externally applied suspension

eg :Calamine lotion.

 Parenteral suspension
eg: Procaine penicillin G
Insulin Zinc Suspension
10
Based on Proportion of Solid Particles
 Dilute suspension (2 to10%w/v solid)

Eg: cortisone acetate, predinisolone acetate

 Concentrated suspension (50%w/v solid)

Eg: zinc oxide suspension

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Based on Electrokinetic Nature of Solid Particles
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 Flocculated suspension

 Deflocculated suspension
Based on Size of Solid Particles

Colloidal suspensions (< 1 micron)

- Suspensions having particle sizes of suspended solid less than

about 1micron in size are called as colloidal suspensions.

13
Coarse suspensions (>1 micron)
Suspensions having particle sizes of greater than about
1micron in diameter are called as coarse suspensions.

Coarse dispersion
Barium sulphate

Nano suspensions (10 ng)

 Suspensions are the biphasic colloidal dispersions of
nanosized drug particles stabilized by surfactants.
Size of the drug particles is less than 1mm.

14
Advantages And Disadvantages
Advantages
15
.Suspension can improve chemical stability of certain drug.
E.g. Procaine penicillin G.

Drug in suspension exhibits higher rate of bioavailability than other

dosage forms.

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

Duration and onset of action can be controlled.

E.g. Protamine Zinc-Insulin suspension.

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

E.g. Chloramphenicol
 Disadvantages
16

 Physical stability , sedimentation and compaction can causes

problems.

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

transport.

 It is difficult to formulate.

 Uniform and accurate dose can not be achieved unless

suspension are packed in unit dosage form.
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 17

 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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 Features Desired In Pharmaceutical Suspensions

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 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 should have pleasing odour , colour and palatability.

 Good syringeability.

 It should be physically,chemically and microbiologically stable.

 Parenteral /Ophthalmic suspension should be sterilizable.

THEORITIC CONSIDERATION OF SUSPENSIONS
20

A knowledge of the theoretic considerations pertaining to

suspension s technology ultimately help formulator to select
ingredients that are

 Appropriate for suspension preparation

 That available for milling

 Mixing equipment
Some theoretic considerations are :
21

 Particle size control.

 Wetting

 Sedimentation

 Brownian movement

 Electokinetic

 Aggregation
 22

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

-Too fine particles will easily form hard cake at the bottom
of the container.
Wetting of the particles
23

 Hydrophilic materials (talc, ZnO, Mg 2CO3) 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
24

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
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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 2 gm per

100 ml)

 Particles which freely settle without collision .

 Particles with no physical or chemical attraction.

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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

27
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

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The sedimentation volume gives only a qualitative account of
flocculation.

Fig : Suspensions quantified by sedimentation volume (f)

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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.
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.

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
that
their size is below critical radius (r).

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 Brownian movement can be observed,

 If particle size is about 2 to 5mm,

 When the density of particle & viscosity of medium are

favorable.

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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

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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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 As the potential drops off rapidly
b at first, followed more gradual
decrease as the distance from the surface increases.

 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.

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Electric Double Layer
36

tightly diffuse
bound

+ - + -
+ - + - +
+ - - + - electroneutral
+ - + + + +
- + - bulk
+ - - -
+ - + +

gegenion

zeta potential

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

 Since this potential, rather than the Nernst 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.

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

 Thus the phenomenon of flocculation and de flocculation

depends on zeta potential carried by particles.

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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.

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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.

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 Rheology of Suspensions
41

 flocculated particles in concentrated suspensions

 exhibit pseudoplastic or plastic flow
 system resists flow until a yield stress is reached
 below s substance is a solid

 deflocculated systems exhibit Newtonian behavior

 Thixotropy
42
 slow recovery of viscosity lost through shearing
 applies only to shear thinning materials
 gel-sol-gel transformation (hysteresis)

 thixotropy is desirable because :

 gel state resists particle settling
 becomes fluid on shaking and then readily dispensed
stress, s

shear rate
 :
FORMULATION OF SUSPENSIONS

 The formulation of a suspension depends on whether the

suspension is flocculated or deflocculated.

 Three approaches are commonly involved

1. Use of structured vehicle

2. Use of controlled flocculation
3. Combination of both of the methods

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 Controlled Flocculation
44

electrolytes
 most widely used
 reduce zeta potential
 decrease force of repulsion
 change pH
 bridge formation
alcohol
 reduction in zeta potential
surfactants
 form adsorbed monolayers on particle surface
 efficacy is dependent on charge, concentration
 Controlled Flocculation
45

 polymers
 adsorb to particle surface
 bridging
 viscosity, thixotropy
 protective colloid action
 most effective
Flow chart of formulation of suspension

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 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.

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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.

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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.

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 Controlled flocculation

° Controlled flocculation of particles is obtained by

adding flocculating agents, which are:

(1) electrolytes

(2) surfactants

(3) polymers

50
 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

51
 INGREDIENTS FOR

FORMULATION OF SUSPENSIONS

52
.

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.
53
 Suspending agents

 Suspending agent are also known as hydrophilic colloids

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

Suspending agent form film around particle and decrease

interparticle attraction.

 Most suspending agents perform two functions

i.e. besides acting as a suspending agent

they also imparts viscosity to the solution.

54
 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.
.

55
Stability pH range and concentrations of most commonly used suspending agents.
Suspending agents Stability pH Concentrations
range used as 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

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List of Suspending Agents
Alginates
•Methylcellulose
•Hydroxyethylcellulose
•Carboxymethylcellulose
•Sodium Carboxymethylcellulose
•Microcrystalline cellulose
•Acacia
•Tragacanth
•Xantham gum
•Bentonite
•Carbomer
•Carrageen
•Powdered cellulose
•Gelatin
57
Alginates

 Alginate salts have about same suspending action to that

of Tragacanth.

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

due to polymerization.

Alginate granules

58
 Maximum viscosity is observed at a pH range of 5-9 of
alginate.

 Chemically alginates are polymers composed of mannuronic

acid and glucuronic acid monomers.

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

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

59
 Methylcellulose

 Methylcellulose is available in several viscosity grades.

 The difference in viscosity is due to difference in methylation

and polymer chain length.

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

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

on on
Methyl cellulose Gel form Solution form
heating cooling

Methyl cellulose
powder

60
Hydroxy ethylcellulose:

 Hydroxyethylcellulose (HEC) is another good

suspending agent having somewhat similar characteristics
to methylcellulose.

 In HEC hydroxyethyl group is attached to cellulose chain.

 Unlike methylcellulose, HEC is soluble in both hot and cold

water
and do not form gel on heating.

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Carboxy methylcellulose (CMC)

 Carboxy methylcellulose is available at different viscosity grades.

 Low, medium and high viscosity grades are commercially

available.

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

temperature rises to 40 ºC from 25 ºC.

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

is widely accepted.

62
Microcrystalline Cellulose (MCC; Tradename-Avicel)

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

thixotropic gels.

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

they facilitate dispersion of MCC.

63
The advantages of MCC:

 Alginate complex compositions are that they provide excellent

stability.

 Formulation of dry powder suspensions with MCC;

Alginate complexes produce an excellent dry readily hydratable

and dispersible formulation for reconstitution.

64
 Wetting Agents
 Hydrophilic materials are easily wetted by water while hydrophobic
materials are not.

 However hydrophobic materials are easily wetted by non-polar

liquids.

 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 is less than 0.5 %.

65
.

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 following advantages

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

 No toxicity. Safe for internal use.
66
 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.

 They cause deflocculation of suspension because force of

attraction is declined. e.g. acacia, tragacanth, alginates, guar
gum.

67
 Solvents
 The most commonly used solvents used are alcohol,
glycerinpolypropylen, polyethylene glycol and e 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.

68
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 are also dependent on the pH of the system.

69
. 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.

70
 Osmotic Agents
 They are added to produce osmotic pressure comparable to
biological fluids when suspension is to be intended for
ophthalmic or injectable preparation.

 Most commonly used osmotic agents are

 dextrose,
 mannitol
 sorbitol.
 sodium chloride,
 sodium sulfate
 glycerol.

71
 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.

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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

73
 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.

74
Eg:
Acacia Ginger Sarsaparilla
syrup
Anise oil Glucose Spearmint oil
Benzaldehyde Glycerin Thyme oil

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 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%)

 Color aids in identification of the product.

 The color used should be acceptable by the

particular country.

76
Most widely used colors are as follows.
· Titanium dioxide (white)

· Brilliant blue (blue)

· Indigo carmine(blue)

· Amaranth (red)

·Tartarazine Annatto seeds

(yellow)
Annatto seeds(yellow to orange)

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 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 %

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Artificial sweetening agents

•Sodium cyclamate

•Sodium saccharin

•Aspartame

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 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.

80
 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,

Sodium sulfateacetone

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 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.

82
 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.

83
Step 2:
 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.

84
 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.

85
 The dispensing of suspensions
Variations: 86
 If wetting agents are included in the
formulation, add them before forming the
paste.
 If syrup and/or glycerol are in the formulation,
use this rather than water to form the initial
paste.
 If soluble solids are being used, dissolve them
in the vehicle before or after making the paste.
 Leave addition of volatile components,
colourings or concentrated flavouring
tinctures such as chloroform spirit, liquid
liquorice extract and compound tartrazine
solution until near the end.
 Packaging of Suspensions

Introduction

 Pharmaceutical suspensions for oral use are generally packed

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

 Parenteral suspensions are packed in either glass ampoules or

vials.

87
Ideal Requirements of Packaging Material

 It should be inert.

 It should effectively preserve the product from light,

air, and other contamination through shelf life.

 It should be cheap.

 It should effectively deliver the product without any

difficulty.

88
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.

89
 Amber glass doesn’t allow U.V light to pass through.

 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

90
Disadvantages of Glass Materials:

They are fragile.

They are very heavy as compared to plastic so

handling and transport is difficult.

 Most important disadvantage of glass that

glass constituents get extracted into the product.

91
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.

92
Advantages Of Plastic Material:

•Non breakability.
•Light weight.
•Flexibility.

Materials used: -

Polyethylene, PVC, polystyrene, polycarbonate etc

93
Closure And Liners

With an exception of ampoules all containers required

elastomeric closure.

closures

liners

94
Factors affecting in selecting closure:

Compatibility with product.

 Seal integrity.

It should be stable throughout the shelf life.

Factors affecting in selecting liner:

 Chemical resistance.
 Appearance
 Gas and vapor transmission.
 Removal torque.
 Heat resistance.
 Shelf life.
 Economical factors
95
 STORAGE REQUIREMENTS & LABELLING

Labelling:

Shake well before use

Do not freeze

Protect from direct light(for light sensitive drugs)

 In case of dry suspensions powder the specified amount of

vehicle to be mixed may indicated clearly on label.

96
Label:

97
 STORAGE :

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

in a refrigerator

 Freezing at very low temperatures should be avoided which may

lead to aggregation Of suspended particles

Stored at controlled temperature from 20-250c

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 Sus pe ns i o ns
n o f
Evaluatio

99
Evaluation of Suspensions

 Sedimentation method

 Rheological method

 Electro kinetic method

 Micromeritic method

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Sedimentation method :

Two parameters are studied for determination of

sedimentation.

1. Sedimentation volume,

2. Degree of flocculation.
,

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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
and Vo = initial height of total suspension

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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.
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 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.

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Electro kinetic method

 Measurement of Zeta-potential using Micro electrophoresis

apparatus & ZetaPlus (Brookhaven Instruments Corporation, USA)

It shows the stability of a disperse system.

Micro-Electrophoresis
Apparatus Mk I

ZetaPlus

105
Zeta potential

The zeta potential of the formulated suspensions was determined

using 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 (1.33)

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

14, 21 and day 28 post formulation.

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 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

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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.

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 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

Freeze-thaw testing freezer INNER CHAMBER

109
 pH MEASUREMENT

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

the Quality control testing .

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

measurement of pH.

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METHODS FOR pH MEASUREMENT:

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

sample.

 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.

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 If greater accuracy is required a pH meter should be
used.

 A typical pH meter consists of a special measuring glass

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

112
VISUAL INSPECTION:
 With visual inspection, the ingredients and the final
products are carefully examined for purity and for
appearance .

 Physical appearance of products for patient adherence

and compliance is critical so it should be:
Good looking
Elegance in appearance .

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 DISSOLUTION STUDY OF SUSPENSIONS

Introduction:

The drug release from suspensions is mainly through dissolution.

 Suspensions share many physico-chemical characteristics of

tablet & capsules with respect to the process of dissolution.

 As tablets & capsules disintegrate into powder and form

suspensions in the biological fluids.

 So dissolution is carried as follows

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Dissolution Testing

Official Method (Conventional Method):

 It is known as paddle method.

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The 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

Dissolution profile of the 500 mg sample suspension is

 determined at 37°C in 900 ml of

 pH 7.2 phosphate buffer using

 the FDA paddle method at 25 RPM.

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

 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.

 Withdraw 5 ml of dissolution medium (and replace

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

 Immediately filter through a 0.2 µm membrane and

analyze.

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Innovations of
suspensions

118
Innovations of suspensions

1. Nano suspensions

2. Taste masked pharmaceutical suspensions

3. Sustained release suspensions

119
 1. Nano suspensions:

 Nano suspensions are the biphasic colloidal dispersions of

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

They 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.

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121
 2.Taste Masked Pharmaceutical
Suspensions .

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

in most of the dosage forms containing bitter drugs.

 In case of suspensions also taste masking is being applied

to
mask bitterness of drugs formulated.

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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.

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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

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b. Encapsulation with a Basic Substance

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

insoluble at high pH.

The mixer is then encapsulated with a polymer (cellulose

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

The drug after encapsulation are suspended, dispersed or

emulsified in suspending medium to give the final dosage form.

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c. Coating and pH Control
Those drugs which are soluble at high pH are preferably be
maintained in a suspension at a low pH where the drug exhibit
maximum insolubility.

 Similarly drugs which are soluble at low pH are preferably

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

Also applying polymeric coating to the drug substance avoids

solubilization of drug when administered providing taste masking.

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 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,)

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 Sustained Release Suspensions

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

action of drug being formulated without affecting onset of
action.

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

formulated as suspension by insoluble polymer coating.

 The polymer coating provides sustained release and also masks

the taste of the bitter drug.

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 The polymer used for sustained release in suspension is
as follows as
 Ethyl cellulose,
Eudragit,
Cellulose acetate, etc.

 The main advantage of sustained release

suspension is decrease in dosing frequency.

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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.

130
 REFERENCES
 Subramanyam C.V.S., Second edition, “Suspensions” Text
Book of Physical Pharamaceutics, PageNo. 374-387.

 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.

131
 Cooper & Gun, Sixth edition, “Dispersed system” Tutorial
Pharmacy, Page No. 75-78.

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

The Science of Dosage Form Design, Churchill Livingstone,
Edinburgh 2002, PageNo. 84-86, 273.

132
 Martin A. Fourth edition, “Coarse dispersion”
Physical Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2001, Page No. 479-481.

 Remington, Twentieth edition, “Colloidal

Dispersions” The Science and Practice of
Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2000, Page No. 298-307.

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