2. Learning Objective
At the end of this session, students will be able to:
Define Suspension/ pharmaceutical suspension
Describe reasons for formulation of suspension
List properties of suspension
Explain three parameters for formulation of suspension
Describe surfactants and types of surfactants
Describe suspending agents and its types
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3. Definition
• Suspensions are a type of dispersed system in which one
substance (dispersed phase) is distributed in particulate form
throughout another (continuous phase).
• Dispersed system= Dispersed phase(internal phase) + Dispersed
medium(external phase)
• Internal phase is dispersed uniformly as finely divided insoluble
particles throughout the external phase.
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4. • The external phase (suspending medium) is generally
aqueous in some instance, may be an organic or oily liquid for
non oral use.
• 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 or
vehicle).
Each phase can exist in solid, liquid, or gaseous state .
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5. • According to the size of particles of a dispersed phase,
dispersion system can be classified as
• Colloidal dispersion: particles in the dispersion phase are greater than 1m
• Coarse dispersion: particles in the dispersion phase are greater than 1m
Example: suspension and emulsion
• Pharmaceutical suspensions are suspension when the particles
constituting the internal phase of the suspension are
therapeutically active.
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6. Reasons for preparing suspension
• 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.
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7. Properties of Good Suspension
• It should be chemically and physically stable during
administration and storage.
• It should settle slowly and re-disperse readily up on gentle
shaking of the container
• After shaking, the medicament should stay in suspended long
enough for a dose to be accurately measured
• It is removed easily from the container (pourable)
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8. • The sediment should not form aggregate or cake.
• Comparatively free from large particulate matter, with
acceptable color, odor and taste.
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9. Types of suspension
• Depending on the properties of dispersed phase, suspensions are
classified into four groups:
A. Suspension containing diffusible substances
• They contain easily dispersible solids
• They are light and easily wettable substances
• Readily mixed with water and on shaking diffuse evenly
throughout the liquid long enough to ensure even distribution
and a dose to be measured
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10. • These sediment sufficiently slowly to enable satisfactory dose
removal after re-dispersion
• Example:
• Light kaolin
• Magnesium trisilicate
• Light calcium carbonate, Magnesium carbonate
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11. B. Suspensions containing indiffusible solids
• These are insoluble powders and will not remain evenly
distributed in a vehicle long enough to ensure uniformity of
dose
• These sediment too rapidly and require the addition of other
materials to reduce sedimentation rate to an acceptable level.
• Needs thickening agent:
• Increase viscosity to prevent falling down of particles
• Avoid collision or decrease density of particles
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13. C. Suspensions containing poorly wettable substance
• This particles are both insoluble and poorly wettable in water
• Interfacial tension between particles and water is high i.e. not
diffusible in water
• Wetting agents (surfactants) decrease interfacial tension i.e.
affinity of the particles to the surrounding environment is
increased and decrease the interparticulate force.
• Example: Sulfur lotion, Hydrocortisone
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14. D. Suspensions of precipitate forming solids
• Resinous materials when mixed with water become precipitated
• Thickening agent is used
• Example: Compound bentonite tincture, Tolune tincture
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15. Formulation of suspension
The three steps that can be taken to ensure formulation of an
elegant pharmaceutical suspension are:
1. Control particle size
2. Use thickening agent to increase viscosity of the vehicle by
using suspending agents or viscosity increasing agents
3. Use of a wetting agent/ surfactants
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16. Problems encountered during
formulation
• Various factors need to be considered when formulating
insoluble solids in to suspension:
A. Sedimentation
• This is a phenomenon which occurs in dispersed system where
the dispersed particles settle to the bottom of the container.
• This occurs because the particles are too large to remain
permanently suspended in the vehicle.
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17. • The factors affecting the rate of sedimentation of a particle are
described in Stokes’ equation.
• Stokes’ equation
V= 2r2 (ρ s- ρ o ) g or
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V= d2 (ρ s- ρ o ) g
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18. Where, V. = rate of sedimentation
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
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19. A decrease in settling rate in a suspension may be
achieved by:
• Reducing the size of the particle
• Increasing the density of the liquid continuous phase
• Increasing the viscosity of the continuous phase but greater
increase in the viscosity may lead to problem in pouring,
syringebility and re-dispersibility of suspension.
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20. B. Flocculation
• It is a natural tendency towards aggregation of particles
• Solution:-
• Deflocculation in separate viscous medium
• Flocculation by controlling volume, type of sediment and pourability
C. Wetting problem
• Wetting agents increase the affinity of the particles towards the
surrounding medium but decreases inter particular forces
• Example: Ethanol, glycols, glycerol
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21. Surface active agents/ surfactants
Surfactants decrease the interfacial tension between drug
particles and liquid and thus liquid is penetrated in the pores of
drug particle displacing air from them and thus ensures
wetting.
Surfactants in optimum concentration facilitate dispersion of
particles.
Generally we use non-ionic surfactants but ionic surfactants
can also be used depending upon certain conditions.
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22. • Disadvantage of surfactants:-
They have foaming tendencies
They have bitter taste
They interact with preservatives and may decrease
antimicrobial activity eg. Polysorbate 80
• Surface active agents are divided into four main groups
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23. A. Anionic agents:
• Commonly used surface active agents
• Are those containing carboxylate, sulfonate and sulfate ion.
• Example: Sodium lauryl sulfate
B. Cation agents
• Quaternary ammonium salts
• May act as preservative
• Cause lysis of cells
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24. C. Amphoteric agents
• Are majorly agents containing carboxylate or phosphate
groups
• Contain both anion and cation
D. Non ionic agents
• Are the major class of compounds used in pharmaceutical
systems
• Are suitable with respect to compatibilities and stabilities
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25. Example: 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.
Less foaming tendencies however it should be used at
concentration less than 0.5%.
Compatible with most of the adjuvant.
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26. Suspending agents/Thickening agents
• Suspending agents are substances that are used to keep finely
divided insoluble materials suspended in a liquid media by
preventing there agglomeration (coming together) and by
imparting viscosity to the dispersion media so that the particles
settle more slowly.
• Care must be taken when selecting a suspending agent for oral
preparations as the acid environment of the stomach may alter
the physical characteristics of the suspension and therefore the
rate of release of the drug from suspension.
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27. They can be obtained from different sources:
I. Natural polysaccharides (Acacia, Tragacanth, Sodium
aliginate and Starch)
II. Inorganic semi-synthetic agents
III. Synthetic agents
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28. I. Natural polysaccharides
• The main problem with these agents is their natural variability
between batches and microbial contamination.
a. Acacia
• Are exudates of Acacia senegal and other species of acacia
• 40 acacia is equivalent to 1.25 Tragacanth solution
• Rarely used for external preparation
• May need preservative and not suitable for ingredients sensitive to
oxidation
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29. b. Tragacanth
• It has high thickening power
• Can be used in combination
• Less sticky and can be used for external preparation
• Outside a PH 4 – 7.5, it loses its viscosity
• For prolonged storage, preservative is needed
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30. c. Sodium Alginate
• Consists mainly sodium salts of aliginic and polyuronic acid from sea weeds
• The mucilage should stand overnight before use
• Maximum viscosity is achieved at PH = 7
• Incompatible with cationic compounds
d. Starch
• Usually used in combination with compound tragacanth powder
• Can also be used in combination with sodium carboxycellulose
• Used for internal use
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31. II. Semi synthetic polysaccharides
• They are derived from the naturally occurring
polysaccharides(cellulose).
• They are Na, K, or Ca salt of particularly acetylated or
methylated polysaccharides of high molecular weight.
• Examples: MC, HMC, EC, NaCMC, MCC(Avicel) and Xanthan
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32. a. Xanthan
• It consists of the sodium salt of partially acetylated polysaccharide of high molecular
weight.
• Soluble in hot or cold water
b. Water soluble cellulose
• Methyl cellulose(MC)
• Are soluble in cold but insoluble in hot water
• They are non ionic, stable over wide range of PH.
• Up on heating gel is formed and up on cooling solution is formed
• Used for both internal and external use.
• Incompatible with some solvents, chlorocresol, resorcinol, tannic acid and silver
nitrate
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33. b. Water soluble cellulose
• Methyl cellulose(MC)
• Are soluble in cold but insoluble in hot water
• They are non ionic, stable over wide range of PH.
• Up on heating gel is formed and up on cooling solution is
formed
• Used for both internal and external use.
• Incompatible with some solvents, chlorocresol, resorcinol,
tannic acid and silver nitrate
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34. • Hydroxyethyl cellulose(HEC)
• Soluble in cold and hot water
• More densre than MC
III. Synthetic agents
• These are agents introduced to overcome the variable quality of natural
products
A. Carbomer (carboxy vinyl polymer)
• They have low viscosity but when neutralized, it becomes viscous gel
• Its viscosity is higher over PH 6-11
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35. B. Colloidal silicon dioxide
• Prepared by vapor phase hydrolysis of silicon compound
• At about 12% it gives soft get but usually used as suspending
agent at 1.5-4%
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36. Preservation of suspensions
• Addition of preservatives into suspensions is important.
• This is because suspensions would have water as vehicle and
naturally occurring additives such as acacia and tragacanth as
sources of microbial contamination and microbes
respectively.
• Useful preservatives include chloroform water, Benzoic acid
and Hydroxy benzoate.
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37. STABILITY OF SUSPENSIONS
Factors that contribute to appreciable stability of a suspension
include:
a) Small particle size- reducing the size of the dispersed
particle increases the total surface area of the solid. The
greater the degree of subdivision of a given solid the larger
the surface area. The increase in surface area means also an
increase in interface between the solids and liquids leading
to an increase in viscosity of a system.
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38. • Increasing the viscosity – increasing the viscosity of the
continuous phase can lead to the stability of suspensions.
This is so because the rate of sedimentation can be
reduced by increase in viscosity. Viscosity increase is
brought about by addition of thickening agents to the
external phase. In water these must be either soluble or
swell. It is important to note that the rate of release of a
drug from a suspension is also dependent on viscosity. Of
a product. The more viscous the preparation, the slower is
likely to be the release of a drug. Sometimes this property
may be desirable for depot preparations.
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39. C. TEMPERATURE.
• Another factor which negatively affects the stability and
usefulness of pharmaceutical suspensions is fluctuation of
temperature. Temperature fluctuations can lead to caking and
claying.
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40. Pharmaceutical application of
suspensions
• Drugs that have very low solubility are usually formulated as
suspensions
• Suspended dosage form of insoluble medicaments are easy to
swallow
• Insoluble derivatives in suspension may be more palatable than
soluble derivatives in solution
• They act as adsorbent of toxins in GIT in powder form
• Example. Kaolin and chalk
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41. • Increase rate of dissolution in GIT as compared to solid dosage
forms
• Insoluble form of drugs may prolong the action of a drug by
preventing rapid degradation of the drug in the presence of
water
• When the drug is unstable in contact with the vehicle,
suspension are prepared immediately prior to use
• Drugs which degrade in aqueous solution may be suspended
in a nonaqueous phase
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42. • IM or SC preparation are often formulated as suspensions
to prolong drug release
• Thin coat of insoluble medicaments on the skin can be
achieved in form of suspension
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43. Advantage and Disadvantage of
Suspensions
Advantages Of Suspensions
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. bioavailability is in following order,
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
palmitate
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44. Disadvantage
• The preparation must be shaken prior to measuring a dose
• Accuracy of dosage is less reliable than with solution
• Storage may lead to change in the disperse system
• Bulk, inconvenient, high susceptibility to loss
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45. Special labels and advice for
suspensions
All pharmaceutical suspensions should be properly labelled.
Additional information in addition to the product name and
directions for use is the inclusion of the direction “shake the
bottle well before use” as some sedimentation of medicament
would normally be expected..
Other labelling information include directions to store in a
cool place, expiry date.
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46. Containers for packaging
• Suspensions should be packed in amber coloured bottles- plain
for internal use and ribbed for external use.
• There should be adequate air space above the liquid to allow
shaking and easy pouring.
• A 5ml medicine spoon or oral syringe should be given when the
suspension is for oral use
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