Suspensions

06/06/16

BA-FP-JU-C

suspensions
A suspension: is a disperse system in which
one substance (the disperse phase) is
distributed in particulate form throughout
another (the continuous phase) (i.e. at least
2 phases).
According to the particle size of the
dispersed phase, suspensions are divided
into:
Coarse suspension: which is a dispersion of
particles with a mean diameter greater than 1
m.
Colloidal suspension is a dispersion of particles
with a mean diameter less than 1 m.

06/06/16

BA-FP-JU-C

Pharmaceutical application of suspensions

Why suspensions?
Against solid dosage forms:
If patient has a difficulty of swallowing solid dosage
forms (a need for oral liquid dosage form).
Faster rate of dissolution and oral absorption than
solid dosage forms, yet slower than solutions.
Bulky insoluble powders as kaolin or chalk are better
formulated as suspensions so that they are easier to
take.

06/06/16

BA-FP-JU-C

Pharmaceutical application of suspensions

Why suspensions?
Against solutions:
Drugs that have very low solubility are usefully formulated as
suspensions.
Drugs that have an unpleasant taste in their soluble forms
(e.g., chloramphenicol (soluble) vs. chloramphenicol palmitate
(insoluble )).
Prolongation of effect (e.g. I.M and S.C. suspensions).
Stability and instability issues:
Insoluble forms of drugs may prolong the action of a drug by
preventing rapid degradation of the drug in the presence of
water (e.g., Oxytetracycline hydrochloride (soluble, hydrolyses
rapidly) vs oxytetracycline calcium salt (insoluble, stable).
Non-aqueous suspensions (tetracycline hydrochloride in
coconut oil)
Reconstitution (ampicillin suspension).
06/06/16

BA-FP-JU-C

Properties of a good pharmaceutical

suspension
There is ready redispersion of any sediment
which accumulates on storage.
After gentle shaking, the medicament stays
in suspension long enough for a dose to be
accurately measured.
The suspension is pourable.
Particles in suspension are small and
relatively uniform in size. so that the
product is free from a gritty texture.

06/06/16

BA-FP-JU-C

Formulation of suspensions
Formulation problems
1. Sedimentation.
2. Thermodynamic instability.
3. Wetting.

06/06/16

BA-FP-JU-C

Sedimentation
The factors affecting the rate of sedimentation are in Stokes' equation:

Where v= velocity of sedimentation of a spherical particle of radius r,

and density , in a liquid of density , and viscosity , and where g is
the acceleration due to gravity.

06/06/16

BA-FP-JU-C

Thermodynamic instability

Interfacial free energy (IFE).

IFE = Interfacial tension * surface area
Flocculation
Aggregation

06/06/16

BA-FP-JU-C

Flocculation
The natural tendency of particles towards aggregation will
determine the properties of a suspension. Whether or not a
suspension is flocculated or deflocculated depends on the relative
magnitude of repulsive/attractive forces between particles.
Deflocculated suspension: the dispersed solid particles remain
separate and settle slowly. However, the sediment that eventually
forms is hard to redisperse and is described as a 'cake' or clay.
Flocculated suspension, individual particles aggregate into clumps
or floccules in suspension. Because these flocs are larger than
individual particles, sedimentation is more rapid, but the sediment
is loose and easily redispersible. Excess flocculation may prevent
'pourability' due to its effect on rheological properties.
The ideal is to use either a deflocculated system with a sufficiently
high viscosity to prevent sedimentation, or controlled flocculation
with a suitable combination of rate of sedimentation, type of
sediment and pourability.

BA-FP-JU-C
06/06/16

Wetting
The insoluble medicament may be :
Diffusible solids (dispersible solids): These are insoluble
solids that are light and easily wetted by water. They mix
readily with water, and stay dispersed long enough for an
adequate dose to be measured. After settling they
redisperse easily. Examples include magnesium trisilicate,
light magnesium carbonate, bismuth carbonate and light
kaolin.
Indiffusible solids: Most insoluble solids are not easily
wetted, and some particles may form large porous clumps
in the liquid, whereas others may remain on the surface.
These solids will not remain evenly distributed in the
vehicle long enough for an adequate dose to be
measured. They may not redisperse easily. Examples for
internal use includes aspirin, phenobarbital, sulfadirnidine
and chalk, and for external use calamine, hydrocortisone,
su1phur and zinc oxide.
06/06/16

BA-FP-JU-C

Wetting
Because of the high interfacial tension between
indiffusible solids and water; air may be trapped in these
poorly wetted particles which causes them to float to the
surface of the preparation and prevents them from being
readily dispersed throughout the vehicle.
Wetting of the particles can be encouraged by reducing
the interfacial tension between the solid and the vehicle,
so that adsorbed air is displaced from solid surfaces by
liquid.
Suitable wetting agents have this effect, but decrease
inter-particular forces thereby affecting flocculation.
06/06/16

BA-FP-JU-C

Wetting
Wetting agents:
Hydrophilic colloids such as acacia and tragacanth can act
as wetting agents. However, care should be taken when
using these agents as they can promote deflocculation.
Intermediate HLB (hydrophilic-lipophilic balance) surfactants
such as polysorbates (tweens) and sorbitan esters (spans)
are used for internal preparations. Sodium lauryl sulphate
and quillaia tincture are used in external preparations.
Solvents such as ethanol, glycerol and the glycols also
facilitate wetting.

06/06/16

BA-FP-JU-C

Suspending agents
Suspending agents increase the viscosity of the vehicle,
thereby slowing down sedimentation.
Most agents can form thixotropic gels which are
semisolid on standing, but flow readily after shaking.
Care must be taken when selecting a suspending agent
for oral preparations.
Suspending agents can be divided into five broad
categories: natural polysaccharides, semi-synthetic
polysaccharides, clays, synthetic thickeners and
miscellaneous compounds.
06/06/16

BA-FP-JU-C

Suspending agents
Natural polysaccharides
The main problem with these agents is their natural variability
between batches and microbial contamination.
These materials should not be used externally as they leave a
sticky feel on the skin.
They include tragacanth, acacia gum, starch, agar, guar gum,
carrageenan and sodium alginate.
Tragacanth:
Is a widely used suspending agent and is less viscous at pH 47.5.
As a rule: 0.2g tragacanth powder is added per 100 mL
suspension or 2g compound tragacanth powder per 100 mL
suspension. Compound Tragacanth Powder BP 1980 contains
tragacanth, acacia, starch and sucrose and so is easier to use.
Tragacanth powder requires to be dispersed with the insoluble
powders before water is added to prevent clumping .
06/06/16

BA-FP-JU-C

Suspending agents
Semi-synthetic polysaccharides
These are derived from the naturally occurring
polysaccharide cellulose.
Examples include
Methylcellulose (Cologel , Celacol)
Hydroxyethylcellulose (Natrosol 250)
Sodium
carboxymethylcellulose
(Carmellose
sodium)
Microcrystalline cellulose (Avicel).

06/06/16

BA-FP-JU-C

Suspending agents
Clays

These
are
naturally
occurring
inorganic materials which are mainly
hydrated silicates.
Examples include bentonite and
magnesium
aluminium
silicate
(Veegum).

06/06/16

BA-FP-JU-C

Suspending agents
Synthetic thickeners:
These were introduced to overcome the variable
quality of natural products.
Examples include:
Carbomer (Carboxyvinyl polymer, Carbopol),
Colloidal silicon dioxide (Aerosil, Cab-o-sil)
Polyvinyl alcohol (PVA).
Miscellaneous thickeners:
Gelatin used as a suspending agent and a viscosity
increasing agent

06/06/16

BA-FP-JU-C

Preservation of a suspension
Water is the most common source of microbial
contamination.
Also the naturally occurring additives such as acacia and
tragacanth may be sources of microbes and spores.
Preservative action may be diminished because of
adsorption of the preservative onto solid particles of drug,
or interaction with suspending agents.
Useful preservatives in extemporaneous preparations
include
chloroform
water,
benzoic
acid
and
hydroxybenzoates.

06/06/16

BA-FP-JU-C

Formulation of suspension
1. Control particle size. On a small scale.
this can be done using a mortar and
pestle. to grind down ingredients to a
fine powder.
2. Use a thickening agent to increase
viscosity of vehicle by using suspending
or viscosity-increasing agents.
3. Use a wetting agent.
06/06/16

BA-FP-JU-C

The dispensing of suspensions

Method of preparation
A. Crystalline and granular solids are
finely powdered in the mortar. The
suspending agent should then be
added and mixed thoroughly in the
mortar. Avoid gumming or caking.
B.

06/06/16

Gradual addition of vehicle, make a

paste then continue till become
smooth and pourable, rinse and up to
volume in a tared bottle.
BA-FP-JU-C

The dispensing of suspensions

Variations:
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.
06/06/16

BA-FP-JU-C

Preparation of suspension from

oral solid dosage form

The tablet will be crushed or capsule contents

emptied into the mortar and a suspending agent
added.
A paste is formed with the vehicle and then
diluted to a suitable volume, with the addition
any other
desired ingredients such as
preservative or flavour.
A short expiry of no more than 2 weeks (more
likely to be 7 days) should be given owing to the
lack of knowledge about the stability of the
formulation.
06/06/16

BA-FP-JU-C

Preparation of suspension from

dry powders and granules for
reconstitution

Reconstitution because of chemical or

physical instability.
Loosening of powder from bottom of the
container.
The specified amount of cold, purified water
should then be added, sometimes in two or
more portions with shaking.
some preparations may be prepared
immediately before taking from individually
packed sachets of powder or from bulk
solids.
06/06/16

BA-FP-JU-C

Containers for suspension

Suspensions should be packed in amber
bottles, plain for internal use and ribbed for
external use.
There should be adequate air space above
the liquid to allow shaking and ease of
pouring.
A 5 mL medicine spoon or oral syringe
should be given when the suspension is for
oral use.

06/06/16

BA-FP-JU-C

Special label and advice for

suspension

The most important additional label for

suspensions is 'Shake well before use ',

Store

in

cool

place.

Stability of
suspensions may be adversely affected by
both extremes and variations of temperature.
Some suspensions. such as those made from
reconstituting dry powders, may need to be
stored in a refrigerator.
Extemporaneously prepared and reconstituted
are required to be recently or freshly
prepared, with a 1-4-week expiry date.
06/06/16

BA-FP-JU-C

150ml Kaolin and Morphine Mixture BP.

Master formula 150ml
2g

Light kaolin
30g
Sodium bicarbonate 500mg
Chloroform and
morphine tincture
0.4ml
6ml
Water
to 10ml
150ml
06/06/16

BA-FP-JU-C

7.5g

to

Chalk Mixture, Paediatric BP. Mitte

100ml
Master formula
100ml
Chalk
100mg
2g
Tragacanth
10mg
200mg
Syrup
0.5ml
10ml
Concentrated cinnamon
water
0.02ml
0.4ml
Double strength chloroform
water
2.5ml
50ml
Water
to 5ml
to 100ml
06/06/16

BA-FP-JU-C

Spironolactone suspension 15mg/5ml. Sig.5ml

t.d.s. Mitte 100ml. For a 4-year-old child.
Master formula
100ml
Spironolactone q.s.* 300mg
Compound orange spirit 0.2%0.2ml
Cologel 20% 20ml
Water
to 100% 100ml

*q.s. means sufficient

06/06/16

BA-FP-JU-C

Menthol and Eucalyptus Inhalation BP 1980.

Mitte 100ml
Master formula
Menthol
2g
Eucalyptus oil
10ml
Light magnesium carbonate 7g
Water
to 100ml

06/06/16

BA-FP-JU-C

200ml Calamine Lotion BP

Master formula
200ml
Calamine 15g 30g
Zinc oxide
5g 10g
Bentonite 3g 6g
Sodium citrate 500mg
1g
Liquified phenol
0.5ml
1ml
Glycerol 5ml 10ml
Water
to 100ml
to 200ml

06/06/16

BA-FP-JU-C

Key points
Suspensions can be used to administer
an insoluble solid by the oral route.
Suspensions may be used to replace
tablets, to improve dissolution rate, to
prolong action and to mask a bad taste.
Solids may be diffusible or indiffusible
and
require
different
dispensing
techniques.
Stokes' equation can be applied when
formulating a suspension to help ensure
accurate dosage of the drug.
Flocculated particles settle quickly and
redisperse easily, whilst deflocculated
particles settle slowly but tend to cake.
06/06/16

BA-FP-JU-C

Key points
Hydrophobic solids may require wetting
agents.
Suspending agents are added to slow down
the rate of settling of the solid.
Suspending
agents
may
be
natural
polysaccharides,
semi
synthetic
polysaccharides, clays or synthetic polymers.
Some suspensions are made by adding
water to reconstitute manufactured powders
when stability is a problem.
Shake well before use' and 'Store in a cool
place should be part of the labels on a
suspension.
Inhalations are suspensions of a volatile
material adsorbed onto a diffusible solid.
06/06/16

BA-FP-JU-C