SUSPENSION

Definition: Suspenions are the biphasic liquid dosage form of medicament in which the
finely divided insoluble solid particles ranging from 0.5 to 5.0 µ are dispersed in a liquid
medium. Solid particles act as dispersed phase and liquid act as continuous phase.

Classification:

I. Based on General Classes

a. Oral suspension

e.g., Chloramphenicol palmitate suspension

b. Suspensions for external use

e.g., Calamine lotion

c. Parenteral suspension

e.g., Procaine penicillin-G

d. Opthalmic suspension

e.g., Fluromethalone opthalmic suspension

 Based On Proportion of Solid Particles

Dilute suspension (2 to10%w/v solid)

Concentrated suspension (50%w/v solid)

 Based on Electrokinetic Nature of Solid Particles

Flocculated suspension

Deflocculated suspension

 Based on Size of Solid Particles

Colloidal suspension (< 1 micron)

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 Coarse suspension (>1 micron)

Nano suspension (lessthan1000 nm)

Qualities of Good suspension:

 Particles should be small uniform sizes that do not settle rapidly.

 The suspension should pour readily and even from its container.

 It should be chemically inert.

 The suspended particles should not form a cake.

 The product must be physically and chemically stable.

 Must be free from all micro organisms

 Should have agreeable odour, colour and taste.

 Must have therapeutic efficacy.

 Should have desired viscosity.

 Should have good syringeability

 Parenteral/ophthalmic suspension should be sterilizable.

Advantages of Suspension:

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

E.g. Chloramphenicol palmitate

 Easy to swallow the suspended insoluble medicaments.

 Children preferred suspension in comparison to tablets and capsules.

 Allow appropriate quantity of drug reasonably small volume.

 Suspensions gives sustained action

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E.g: Protamine zinc insulin suspension

 Suspension can improve the chemical stability

E.g: Procaine penicillin-G

Drug in suspension exhibits higher rate of bioavailability than other dosage forms.
bioavailability is in following order
Solution > Suspension > Capsule > Compressed tablets > Coated tablets

Disadvantages

• 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 cannot be achieved unless suspension are packed in unit
dosage form.

• All suspensions are required to be shaken before measuring dose.

• Storage of suspension leads to changes in disperse system, especially there is fluctuation

in temperature.

Deflocculated suspension Flocculated suspension

Particles exist in suspension as separate Particles form loose aggregates.

entities.
Rate of sedimentation is slow, since each
particle settles separately and particle
size is minimal.
A sediment is formed slowly.
Sediment becomes very closely packed
and a hard cake is formed.
Supernatant liquid is not clear
Rate of sedimentation is high, since particles
settle as a floc, which is a collection of
particles.
A sediment is formed rapidly.
Sediment is loosely packed and donot form
hard cake is formed.
supernatant liquid is clear

The floccules donot stick to the bottle The floccules stick to the sides of the bottle
Suspension is pleasing in appearance Suspension is not pleasing in appearance
Sediment is difficult to redisperse Sediment is easy to redisperse

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Fig: Differences observed between Flocculated and Deflocculated Suspension

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 Flocs

Cakes

Formulation Aspects:

Flocculation agents: In suspension, the solid particles are well dispersed in dispersed medium.
The dispersion can be improved by adding surfactants. which acts as flocculating agents. Which
reduce the surface tension between material and liquid.

E.g., Sodium lauryl sulphate

Tweens
Spans
Carbowaxes etc

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Thickening agents: (Suspending agents): These are hydrophilic substances, which
form colloidal dispersions with water and increase the viscosity of continuous phase. So that the
solid particles remain suspended for longer time to measure a uniform dose.

e.g., Polysaccarides
Inorganic salts
Synthetic compounds.

Polysaccharides:

Two types of colloids are used

1. Natural polysaccharides
2. Semi synthetic polysaccharides
1. Natural polysaccharides
i. Gum acacia: It is good protective colloid and suspending agent. It is more effective when
it is used as compound tragacanth powder. Compound tragacanth powder BP contains
Acacia 20%, Starch 20% and Tragacanth 15% and sucrose 45%. Compound tragacanth
powder is used in the concentration of 2g/ 100 ml mixture.
ii. Tragacanth: It is a better thickening agent than acacia.It is used as compound tragacanth
powder and tragacanth mucilage to suspend indiffussible substances.
Concentration: ¼th of the volume of the mixture
Starch: Starch is used with other suspending agents because of high viscosity of its
mucilage. It is an ingredient of tragacanth powder
iii. Sodium alginate: It forms more viscous solution when dissolved in water. Its 1% solution
is effective suspending agents.
iv. Semi synthetic:
Cellulose derivatives are used as thickening agents.
i. Methyl cellulose: It is used in the concentration of 0.5 to 2% as thickening agents both
in external and internal preparation.
ii. Sodium carboxy methyl cellulose: It is used in the concentration from 0.25 to 1.0 %
for suspending powders in preparations for oral, external and parenteral use.
iii. Microcrystalline cellulose: It is prepared from wood cellulose by acid hydrolysis.

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 iv. Aluminium hydroxide:
It is used as a suspending agent in suspension containing barium sulphate, calamine and
sulphur.
Synthetic compounds:
Carbomer ( carboxy vinyl polymer): It is used as a thickening agent in the concentration
of 0.1 to 0.4% for internal and external preparations.
Colloidal silicon dioxide: It is colloidal non gritty powder and acts as a suspending
agent in the concentration of 1.5 to 4%. It is dispersible in water to produce colloidal
dispersions.
Inorganic agents:
i. Clays:
Bentonite and aluminium, magnesium silicate is very commonly used as thickening
agents.
Bentonites -2% suspension is used for suspending indiffusible solids in external
preparation.
Aluminium and magnesium silicate is used as thickening agent both external and
internal.
Wetting agents:
 These are the substances which reduce the interfacial tension between the solid particles
and liquid medium. The concentration used is less than 0.5 %.
E.g, Alcohol in tragacanth mucilage
Glycerin in sodium alginate
Poly sorbates etc
 Co-solvents
Some solvents which themselves have high viscosity are used as co-solvents to enhance
the viscosity of dispersion medium:
e.g., Glycerol
Propylene glycol
Sorbitol.
Organoleptic additives:

Colouring agents They are added to impart desired color to suspension and improve elegance.

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 e.g., Tartazine (yellow)
sunset yellow
Amaranth (red)

Buffers: Buffers were added to stabilize the suspension to a desired pH range.

e.g, Citric acid

Sodium citrate

Preservatives

 A suitable preservative is needed to preserve

Suspensions against bacterial growth.
e.g., Benzoic acid
Sodium benzoate
Methyl parabhen
Propyl parabhen etc

Sweetening agent

Which imparts good taste in the preparations.

e.g., Sucrose

Saccharin sodium

Sorbitol etc

Flavouring agent

Which imparts good flavour in the preparation

e.g., orange oil
Lemon oil
Banana flavour etc.

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Stoke’s equation

Velocity of sedimentation expressed by Stoke’s equation

V= 2r2 (ρ s- ρ o ) g or V= d2 (ρ s- ρ o ) g

9 18

Where, Vsed. = sedimentation velocity in cm / sec

d = Diameter of particle

r = radius of particle

ρ s= density of disperse phase

ρ o= density of disperse media

g = acceleration due to gravity

η = viscosity of disperse medium in poise

Methods of dispensing suspension: ( Types)

Suspensions are divided into 4 types according to its methods of dispensing

1. Suspensions containing diffusible solids
2. Suspensions containing indiffusible solids
3. Suspensions containing precipitate forming liquids
4. Suspensions produced by chemical reaction

Suspensions containing diffusible solids

Diffusible solids are not dissolved in water,which are light in weight and readily mix with water.
These solids suspended throughout the liquid for long time after shaking.

General method of dispensing:

 Carefully tare the container

 Finely powder the solid ingredients

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  Mix the insoluble powders in a mortar and enough vehicle to make a smooth cream.
 Add more of vehicle to make it pourable.
 Examine the suspension carefully and if it contains foreign particles, strain through
muslin cloth.
 Rinse the mortar and pestle
 Add any liquid ingredient
 Add more of vehicle to produce the required volume
 Mix thoroughly

e.g., Calcium carbonate

Light magnesium carbonate

Magnesium trisilicate

Light Kaolin etc

Example with Formula:

Magnesium Hydroxide Mixture IP

Magnesium Sulphate 4.75 g

Sodium Hydroxide 1.5 g

Light Magnesium oxide 5.25 g

Chloroform 0.25 ml

Purified water ( Freshly boiled & cooled) qs to 100 ml

Suspensions containing indiffusible solids

Indiffusible solids are not dissolved in water. Do not remain evenly distributed in the vehicle for
sufficient long time to ensure uniformity of dose.

e.g., Calamine
Zinc oxide
Precipitated chalk etc.

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General method of dispensing:

 Carefully tare the container

 Finely powder the solid ingredients
 Mix the insoluble powders in a mortar
 Add Suspending agents.
 Measure ¾th of the vehicle and triturate to form a smooth cream.
 Examine the suspension carefully and if it contains any foreign particles, strain through
muslin cloth in a tared beaker.
 Rinses the mortar with small quantity of vehicle clean it.
 Add any liquid ingredient.
 Add more of the vehicle to produce the required volume.

Formula: Calamine lotion IP

Calamine 5g
Zinc oxide 5g
Bentonite 3g
Sodium Citrate 0.5 g
Glycerin 5 ml
Liquified Phenol 0.5 ml
Purified water qs to 100 ml

Suspensions containing precipitate forming liquids

Certain liquid preparations that is precipitated on addition of water.

e.g., Compound benzoin tincture

Myrrh tincture and tolu tincture

These liquids not only insoluble in water but they form indiffusible precipitates particularly
when salts are present.

They contain resinous matter and when it is mixed with water, it leads to precipitation of resin &
Stick to the sides of the bottle.
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To prevent this a protective colloid tragacanth 1/4th of the total volume (2g/100ml) is dispersed
in total volume.

E.g, Mixture

Rx Potassium iodide 2.0 g

Tincture of lobelia ether 8.0 ml
Tincture of stromonium 16.0 ml
Chloroform water add up to 90.0 ml

Suspension produced by chemical reaction:

 In this preparations, the highly diluted solutions of reactants mixed together so as to form
very finely divided precipitates that can be easily distributed throughout the liquid by
shaking.
 The precipitate formed are diffusible in nature.
 No need of adding any suspending agent.

E.g., Mixture Formula:

Sulphurated potash 5.0 g

Zinc sulphate 5.0 g

Concentrated camphor water 2.5 ml
Water add up to 100 ml

Magnesium Hydroxide Mixture B.P (Milk of magnesia) (Oral suspension):

Mixture Formula: Magnesium Sulphate 4.75 g
Sodium Hydroxide 1.5 g
Light Magnesium oxide 5.25 g
Chloroform 0.25 ml
Purified water ( Freshly boiled & cooled) qs to 100 ml
 Milk of magnesia is used as antacid and laxative.

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  Magnesium hydroxide mixture is an aqueous colloidal dispersion of magnesium
hydroxide.
 Magnesium hydroxide mixture BP contains an aqueous suspension of hydrated
magnesium oxide containing not less than 7% w/w and not more than 8.5% w/w of
magnesium hydroxide.
 It is prepared in part by precipitation reactions between magnesium sulphate and sodium
hydroxide and in part by hydration of magnesium oxide.

Precipitation reaction:

 MgSO4+ 2 N aOH → Mg(OH)2 + Na2SO4

Translucent gelatinous
precipitate.
Hydration reaction:
MgO + H2O → Mg(OH)2
Creamy heavy precipitate.
 Magnesium hydroxide prepared from magnesium sulphate is gelatinous in nature, which
will becomes unpourable on keeping,
where as magnesium hydroxide is prepared from magnesium oxide is heavy and settles
fast.
 Therefore, magnesium hydroxide is prepared by both hydration and precipitation are not
Excessively thick and do not separate rapidly.
 The removal of sulphate ions from the mixture is necessary because sulphates when
given orally in hypertonic solution, draw water into intestine.
 This increases peristalsis and induces a profuse watery stool i.e sulphate laxatives.
 There fore, to avoid the action of sulphates, removal of sulphate is necessary.
 Chloroform is used as the preservative.
 The preparation as a pH of about 10 and therefore it attacks containers of lime soda glass.
 The USP allows inclusion of 0.1% citric acid to minimize this effect.

Procedure:

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  Dissolve the sodium hydroxide in 150 ml of purified water.
 Add the light magnesium oxide, mix to form a smooth cream and add sufficient water to
produce 250 ml.
 Magnesium sulphate is dissolved in another 250 ml of purified water.
 Pour this suspension into a solution of magnesium sulphate.
 Stirred continuously during the mixing.
 The precipitate is allow to settle, then clear liquid is decanted.
 Precipitate is transferred through calico strainer.
 The precipitate is washed with purified water several times, until the precipitate is free
from sulphate ions which can be confirmed by sulphate test.
 Chloroform is dissolved in the above mixture
 The volume is madeup to the required quantity with purified water.
 The suspension is transferred into tightly closed container.

Sulphate test:

 A few drops of White precipitate SO- 4 present

washings + A few
drops of barium
chloride solution. No precipitate SO-4 Absent

SO4 2- + BaCl2 BaSO4

Barium sulphate
precipitate
Category: Antacid
Laxative
Dose: 1- 4 ml -- Antacid
8 -16 ml -- Laxative
Auxiliary label : SHAKE WELL BEFORE USE
Storage: Store in a tightly closed container. Do not keep in a cool place.

Applications of Suspensions:

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  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. Oxytetracycline 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 a suspension.
E.g. Barium sulphate for examination of alimentary tract.

Stability Problems

Physicochemical stability of suspensions is important for maintaining the quality of the product.
Suspension is evaluated by following parameters.

Physical stability:

1. Appearance, Colour and taste

2. pH
3. Specific gravity or density
4. Microscopic examination
5. Particle size
6. Temperature
7. Brownian movement
8. Sedimentation volume
9. Degree of flocculation

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 10. Redispersibility
11. Zeta potential measurement
12. Uniform in drug distribution
13. Viscosity

Chemical stability:

14. Degradation of active ingredients

15. Effect of additives on stability.

physical stability.

Appearance, colour, taste: Suspension must in elegance in appearance and other organoleptic
characteristics like colour and taste also carefully examined.

pH of the suspension: Acidic and alkaline pH influence the rate of decomposition of most
drugs. Many drugs are stable between pH 4 and 8.
Specific gravity or density: Density of solid particle and density of liquid medium is very
important parameter need to consider, during formulation of suspension. In more density
difference between dispersed phase and dispersion medium, particles are rapidly settle at the
bottom. This problem is overcome by adding suspending agent to increase the density of liquid
medium.

Microscopic studies:

The stability of the 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 and
coulter counter method. The microscope can be used estimate and detect changes in particle size
distribution and crystal form. By using these photo micrographs we can determine the changes in
physical properties and stability of suspensions.

Particle size:

Reduce the size of the dispersed particle increases the total surface area of the solid. Greater the
degree of subdivision of a given solid the larger the surface area. The increase in the surface area

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means also increase in interface between the solids and liquids leads to an increase in viscosity of
a system.

Temperature:

Another factor which negatively affects the stability and usefulness of pharmaceutical
suspensions is fluctuation of temperature. Temperature fluctuation leads to caking and Claying.

Brownian movement:

Brownian movement of the particles prevents sedimentation by keeping the dispersed material in
random motion. Brownian movement depends on the particle size, density of dispersed phase
and the density and viscosity of the dispersion medium. Two useful parameters for the evaluation
of suspensions are Sedimentation volume "F"& Degree of flocculation “B”

Sedimentation volume: (F): Sedimentation volume of a suspension is expressed by the ratio of

the equilibrium volume of the sediment, Vu (ultimate volume), to the total volume, Vo of the
suspension

F = Vu/Vo

The value of F provides a qualitative knowledge about the physical stability of the suspension.

F=1 No sedimentation, no clear supppernatant

F= 0.5 50% of the total volume occupied by sediment
F> 1 Sediment volume is greater than the original volume due to formation of floccules
which are fluffy and loose

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Degree of flocculation: (ß): Degree of flocculation is the ratio of the sedimentation volume of
the flocculated suspension, F, to the sedimentation volume of the deflocculated suspension, F¥ ß
= F / F¥

ß = (Vu/Vo) flocculated

(Vu/Vo) deflocculated

ß is a quantitative & more fundamental parameter than F as it relates the volume of flocculated
sediment to that in a deflocculated system.

Re-dispersibility: The settled particles in the suspension are easily redispersible by moderate
shaking. This is determined by the number of upside and down inversions of the suspension in a
transparent bottle. Within 4 to 5 times of moderate shaking, the sediment should be easily re-
disperse the sedimented particles indicates the redispersibility is good. Greater than 15 inversions
indicated caking. Flocculating agents are added to enhance particle “re-dispersibility.

• In contrast to deflocculated particles, flocculated suspensions can always be re-suspended

after over a period of time.
• The best approach is to achieve a controlled flocculation of the particles, where they appear
as floccules.

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Controlled flocculation of particles is obtained by adding flocculating agents, which are

(1) Electrolytes
(2) Surfactants
(3) Polymers
1) Electrolytes:

Dispersed solid particles in a suspension may have charge in relation to their surrounding
vehicle, because of-

• Selective adsorption of a particular ionic species present in the vehicle.

• Ionization of functional group of the particle.

• The ions that gave the particle its charge, are called POTENTIAL-DETERMINING
IONS that serve to repel the particles.

• Immediately adjacent to the surface of the particle is a layer of tightly bound solvent
molecules, together with some ions oppositely charged to the potential-determining ions,
called COUNTER IONS.

• Electrolytes acts as flocculating agents by reducing the electrical barrier between the
particles, thus, decrease the zeta potential, this leads to decrease in repulsion potential and
makes the particle come together to form loosely arranged structure (floccules).

Counterion Shear plan

Surface a- b- c- d-
 -  -  -  -
 -
 
 - -  - 
 -  - 
 -  - -  -
 - 
 -  -
  -

 -  -  -  -
 -  
 -
-  - 
 -  -  -  -
a b c d

Tightly Diffusion Electro-neutral

bound layer region
layer

Fig: Potential ions differences in the suspension

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Zeta potential is the potential difference between the ions in the tightly bound layer and the
electro neutral region. Zeta potential governs the degree of repulsion between adjacent, similar
charged, solid dispersed particles.

E.g:

 If we disperse particles of bismuth subnitrate in water, we find that, they, possess a

large positive charge, or zeta potential.

 Because of the strong forces of repulsion between adjacent particles, the system is
deflocculated.

 The addition of monobasic potassium phosphate to the suspended bismuth subnitrate

particles causes the positive zeta potential to decrease due to the adsorption of the
negatively charged phosphate anion.

 With the continued addition of the electrolyte, the zeta potential falls to zero and then
increases in a negative direction.

 The flocculating power increases with the valency of the ions. Calcium ions are more
powerful than sodium ions because the valency of calcium is two whereas sodium has
valency of one.

2) Surfactants:

• Both ionic and nonionic surfactants could be used to control flocculation, e.g. Tween 80,
Spans, Sodium lauryl sulfate.

• The concentration of surfactants necessary to achieve flocculation is critical since these

compounds may also act as wetting agents to achieve dispersion.

• Optimum concentrations of surfactants bring down the surface free energy by reducing
the surface tension between liquid medium and solid particles.

• The particles possessing less surface free energy are attracted towards each other by van
der-waals forces and forms loose agglomerates.

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 3) Polymers:

 Polymers like Starch, alginates, cellulose derivatives, carbomers, tragacanth are long
chain, high molecular weight compounds containing active groups spaced along their
length.

 These agents act as flocculating agents because part of the chain is adsorbed on the
particle surface with the remaining parts projecting out in the dispersion medium.

 Bridging between these portions leads to the formation of floccules.

 Polymers exhibit pseudo-plastic flow in solution promoting the physical stability of

suspension.

Floculating agent

Solid particles
Fig: Polymer chain is adsorbed on the particles
Floccules
Viscosity:

 Viscosity of suspensions is of great importance for stability and pourability of

suspensions. As we know suspensions have least physical stability amongst all dosage
forms due to sedimentation and cake formation.
 So as the viscosity of the dispersion medium increases, the terminal settling velocity
decreases thus the dispersed phase settle at a slower rate and they remain dispersed for
longer time yielding higher stability to the suspension.
 On the other hand as the viscosity of the suspension increases its pourability decreases
and inconvenience to the patients for dosing increases. Thus the viscosity of suspension
should be maintained within optimum range to yield state and easily pourable
suspensions.

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Chemical instability:

Decomposition of API mainly dissolved drug undergoing oxidation, hydrolysis or other

reactions. Make sure the drug exist in insoluble state. By adjusting the pH, can resolve the
problem.
Moisture: Water catalyses chemical reactions as oxidation, hydrolysis and reduction reaction.
Water promotes microbial growth.
Light: Affects drug stability through its energy or thermal effect which lead to Oxidation
Effect of additives on stability: selection of additives one of important parameter. Additives
affects the density, rheological behaviour and it may affect for sedimentation rate.

Additives are significant influences on crystal growth. E.g: when very fine powder is used a part
of suspending agent will dissolve then precipitate as crystal.

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