9

Biphasic Liquid Dosage

Form-Suspensions

Suspensions are the biphasic liquid dosage form of medicament in

which
the finely divided solid particles ranging from 0.5 to 5.0 micron
are
dispersed in a liquid or semisolid vehicle. The solid particles

disperse phase whereas liquid vehicle

vehicle acts as the continuous
phase.

Suspensions are generally taken orally or by parenteral route. They are

also used for external applications.

The particle size of the disperse phase is very important in the

formulation The suspensions which are meant for

of suspensions.
external application, should have small particle size to avoid grity
feeling to the skin and to cover a greater area of the application.
Moreover, it also helps penetration of solid medicament into the skin
because its smaller particle size gives a faster rate of dissolution. The
suspensions which are meant for parenteral administration shouldhavea
particle size that can pass through the needle. The suspensions which
avoid
are instilled into the eye, should be free from gritty particles to
irritation pain and discomfort. The particle size of the suspended drug

particles should not go beyond 10 micron.

Qualities of a Good Suspension

on
(1) It should settle slowly and should be readily re-disperseu

gentle shaking of the container.

container.
(2) The suspension should pour readily and evenly from its

(3) It should be chemically inert.

(4) The suspended particles should not form a cake.

(5) should be free from large particles
It appearancc.t0
which spoil its
irritation
give a gritty taste to oral preparations and also cause
sensitive tissues when applied externally.
 LIQUID DOSAGE FORM-SUSPENSIONS I87
BIPHASIC
Ch-9

of Suspensions
Classification
are classified into four main classes according to its
Suspensions
use. These are:-
pharmaceutical
(1) Oral suspensions

(2) Parenteral suspensions

(3) Ophthalmic suspensions

(4) Suspension for external use

Oral suspensions
1. : These suspensions are to be consumed by
the patient
by oral route. Oral
suspensions generally contain flavouring
agent and sweetening agentmask the bitter taste of the drug. They are
to

also made palatable by using a suitable derivatives of drugs e.g., chlo

ramphenicol palmitate suspension is prepared to mask the bitter taste of
chloramphenicol. Nowadays suspensions are available in the market in
dry powder form and these are reconstituted by adding a specified
quantity of freshly boiled and cooled water before use e.g., antibiotics in

suspension for paediatric use.

Advantages
(1) It is easy to swallow the suspended insoluble medicaments.

(2) The insoluble derivatives in suspensions is more palatable than

soluble derivatives in solution.

(3) The bulky insoluble powders, such as kaolin and chalk can be
of
administered in suspension in order to act as adsorbents
tract.
toxins or to reduce excess acidity in the gastrointestinal

Disadvantages
to be shaken before measuring a
(1) Al suspensions are required
dose.
as compared to solution.
is less reliable
(2) The accuracy of dosage
may lead to changes in disperse
(3) The storage of suspension
is fluctuations in temperature.
system, especially when there
adminis
: The suspensions which are
2. Parenteral suspensions
parenteral suspensions. These
Ced by parenteral route are
called
qualities:
to fulfil the following
uspensions are required be easily
be such that it can
(1) The particle
size of the drug should
ncedle of the syringe.
pass through the during
in the suspension
not be any crystal growth
()
There should
its storage.
188 DISPENSING
PHARMACY
(iii) The concentration of solid particles in the suspension
between 0.5 to 30%. shouldbe

(iv) The viscosity of the suspension should not interfere

with its
flow
through the syringe needle.

(v) The suspensions should be sterilised.

3. Ophthalmic suspensions : These are not commonly need

compared to eye-drops. These are prepared only in those cases,

when
the drug is insoluble in the desired solvent Or unstable in
liquid form.
These suspensions must fulfil the following conditions:

(i) The particle size of the eye-suspensions should be

fine
enough
so that it should be non-irritating to the eye.

(i) The suspensions should be sterilised.

(ii) These suspension should be isotonic.

(iv) These should have desired viscosity.

(v) The suspension should be packed in a suitable container, so that

it can be easily instilled into the eye.

4. Suspensions for external use :These suspensions are meant for

external use. e.g., lotions, inhalations, ear drops etc. These suspensions
contain very small particles to avoid grittiness. Lotion containing sus
pended particles evaporate when applied to the skin leaving a light
deposit of medicament on the surface. Lotions are easier to apply and
less messy than many other semi-solid external preparations. Calamine
lotion a suspension type preparation which is applied on the skin to
is

provide protective effect. Lotions which are meant for application on

broken or inflamed skin should be free from harmful
microorganisms.

Flocculated and Non-flocculated Suspensions

The suspensions are said to be flocculated. when the individual
particles are in contact with each other and form a network like Strue

ture. Whereas in case of individual

non-flocculated suspensions, the
particle
are the
exists as separate differences
a entity. The following
between flocculated in
and non-flocculated suspensions as given
Table 9.1.
TABLE 9.1
Comparison between Flocculated and Non-flocculated Suspensions

[Link]. Flocculated Suspension Suspension

Non-flocculated
1. Particles forin loose aggregates Individual particle exists as
and form a net work Iike structure.
separate entity.
 Ch-9
BIPHASIC LIQUID DOSAGE FORM-SUSPENSIONS 189

Flocculated Suspension Non-flocculated Suspension

SNo.
2. The rate of sedimentationis high. The rate of sedimentation is slow.

3. Sediment is rapidly formed. Sediment is slowly formed.

A Sediment is easy to redisperse. Sediment is difficult toredisperse.
5 Sediment is loosely packed and Sediment is very closely packed
does not form a hard cake. and a hard cake is formed.

6. Supernatent liquid is clear.

Supernatent liquid is not clear.
7. The floccules stick to the sides The floccules do not stick to the
of the bottle. sides of the bottle.

8. Suspension is not pleasing in Suspensionis pleasing in

appearance. appearance.

Formulation of Suspensions

Following additives are used in the preparationof suspensions:

1. Flocculating agents :In suspensions, the solid particles are well

dispersed in dispersion medium i.e., vehicle. The dispersion can be
improved by adding a surfactant or protective colloid which acts as
flocculating agent. The flocculating by reducing the surface
agent acts

tension and thereby improving the dispersion of solids and

minimise

flocculation e.g., sodium lauryl sulphate,tweens, spans

and carbowaxes,
etc. are commonly used as flocculating agents.
which form
2. Thickening agents : These are hydrophilic colloids
of the con
colloidal dispersions with water and increases the viscosity
remain suspended in it for a
tinuous phase, so that the solid particles

Sufficient long time to measure a uniform accurate dose.

suspensions are classified into

The thickening agents used to stabilise

groups-polysaccharides, inorganic agents and synthetic

hree major
compounds.
are used nowa
: Two types of polysaccharides
(A)Polysaccharides
days. These are:

(a) Natural polysaccharides

1) Gunm acacia :
It is a good protective
colloid and suspending
resinous tinctures.
It is

It is useful in mixtures containing

agent. powder.
it is used
as compound tragacanth
more effective when 20%, tragacanth
powder contains acacia
Compound tragacanth tragacanth powder is
Compound
15%, starch 20%
and sucrose. The
ml of mixture.
of 2g per 100
used in the concentration
 DISPENSING
190 PHARMACY
used
powder is always when the
compound tragacanth vehicle is
chloroform water.
than water or
other
an enzyme oxidase which cause
Acaciacontains deterioration of
So benzoic acid and
oxidisable medicament.
easily
added as antimicrobial agents to preserve the
parahydroxy
benzoic acid are
gum acacia.
suspension containing

(ii) Tragacanth :
It is a better thickening
tragacanth powder
agent than acacia.
or tragacanth
Itis

used as compound mucilage to

indiffusible substances. Tragacanth
suspend heavy mucilage is
vehicle is water or chloroform water,
used, when the in the
the volume of the mixture.
concentration of 1/4th of

(ii) Starch : Starch is sometimes used with other

suspending agents
its mucilage. It is aningredient
because of the high viscosity of

of compound tragacanth powder.

(iv) Sodium alginate : forms a viscous solution when dissolved

It
in

water. Its 1% solution have the same suspending power as that

of tragacanth mucilage.

The following cellulose derivatives are used

as
(b) Semisynthetic:
thickening agent:

(i) Methyl cellulose : It is generally used in the concentrationof 0.5

to 2 per cent as thickening agent both in external and internal

preparations.

(ii) Sodium carboxymethyl cellulose : It is used in the concentration

from 0.25 to 1 per cent for suspending powders in preparations
meant for oral, external and parenteral use.
(ii) Microcrystalline cellulose : It prepared from wood
is cellulose

by acid hydrolysis. It is dispersible in water to produce colloidal

dispersions.

(B) Inorganic agents

(a) Clay :
Bentonite and aluminium magnesium silicate
very

or
is

commonly used as thickening agents. Bentonite is a very pale buff

creamy hygroscopic powder. A 2% suspension is used for suspenume
lotion.
indiffusible solids in external preparations such as calamine
Aluminium magnesium silicate is a Creamy white, colourless and
taste-

less powder. It is used as thickening agent both in external and internal

preparations.

(b)

pension
Aluminium hydroxide
containing
: Itsuspending agent
is used as

barium sulphate,calamine, sulphonamide aand

a
sulphur.
in sus-
 LIQUID DOSAGE FORMSUSPENSIONS 191
BIPHASIC
(h9 compounds

(a)
Synthetic
Carbomer
(carboxy vinyl polymer)

the concentration
of 0.1 to 0.4 per
: It is used
cent for internal
as a

and
thickening
in external
qgent

preparations.
(b) Colloidal
silicon dioxide :
agent in the concentration
It is a white non-gritty powder and
asa to 4%.
of
suspending 1.5

CtS
3. Wettingagents :
These are the substances
which reduce the
tension between the solid particles and liquid
medium, thus
interfacial
a suspension of required quality. This may be
producing
achieved by
a suitable wetting agent which is
absorbed at the solid/liquíd
adding
in such a way that the affinity of the particles for the
interface surround-
medium is increased and the interparticular forces are decreased.
in tragacanth mucilage, glycerinin sodium
alcohol
rexample,
For alginate
benonite dispersion and polysorbate in oral and
or parenteral suspen-
Sions.

The excessive use of wetting agent may cause foaming or may give
had taste or odour to the suspension.

4. Preservatives :A suitable preservative is needed to preserve

Suspensions against bacterial growth. Preservatives selected should be
efective againsta wide range of microorganism. Benzoic acid, sodium
benzoate, methyl paraben and propyl paraben are commonly used as a
preservative in suspensions.

5. Organoleptic additives : Colouring agents, sweetening agents

and flavouring agents are generally incorporated in oral suspensions. A

Suitable perfume and colour is incorporated in suspensions which are

meant for external use.

METHODS OF DISPENSING SUSPENSIONS

The types according to its method of
SUspensions are divided into
4

dispensing:
solids
(1) Suspensions containing diffusible
solids
(2) Suspensions containing indiffusible
liquids
precipitate-forming
5) Suspensions containing
reactions
(4) Suspensions produced by chemical

)Suspensions Containing
Diffusible Solids
which are light
in
There are certain powdered substances the
insoluble suspended throughout
Weight and remain
and readily mix with water
192
DISPENSING
liquid for sufficient long time after shaking. Such PIARMACY
as diffusible solids. For example, calcium substances are
carbonate, light
carbonate, magnesium trisilicate, rhubarb powder and
light magnesium
kaolin.
General method of dispensing
(1) Carefullytare the container.

(2) Finely powder the solid ingredients.

(3) Mix the insoluble powders in a mortar and add

to make a smooth cream. enough vchicle

(4) Add more of vehicle to make it pourable.

(5) Examine the suspension carefully and if it

contains
particles, strain through a muslin cloth into a tared foreign
container.
(6) Rinse the mortar and pestle with
successive volume of
vehicle
until they are quite clean. Transfer the rinsings to the
bottle

(7) Add any liquid ingredient.

(8) Add more of vehicle to produce the required volume and miy

thoroughly by shaking the bottle.

Example 9.1 Prepare and dispense the following suspension.

Light kaolin 12.0 g

Light magnesium carbonate 3.0g
Sodium bicarbonate 3.0 g
Peppermint water add up to 90 ml
Make a mixture.

Direction

Method :
:One
Mix
dose

the weighed
to be taken
quantities
three times

of
a day.
light kaolin, light magnesium

carbonate, sodium bicarbonate a mortar. Measure out 4th of

in und

peppermint water. Out of this add a small amount to the powder anto

uiturate thoroughly until a smooth paste is formed. Then dilute wu it

piece.
remaining amount of peppermint water, strain through muslin
Trans-
Add more of peppermint water to produce the required volume.
fer the suspension to a bottle, 1abel and dispense.

Example 9.2 Prepare and dispense the following suspension.

Bismuth carbonate 1.0 g

Sodium bicarbonate 0.7 g
Tincture belladonna 0.4 ml
Water add upto 30.0 ml
 LIQUID DOSAGE FORM-SUSPENSIONS 193
9 BPHASIC
Make a mixture.
Send 120
m]
: Take two teaspoonful before each

.
meal.
Direction

Method
: Mix the weighed quantities of bismuth carbonate and

bicarbonate. Measured 4th of water Out of this add a small

sOdium and
to the powder triturate thoroughly until a smooth paste is

amOunt diluted it
Then with remaining amount of water, strain through
formed.
piece. Add belladonna and more quantity of water to
tincture
MEslin volume. Transferthe suspension into a bottle, label
produce
the required

nd dispense.
Containing Indiffusible Solids
Suspensions
Indiffusible solids are those substances which do not dissolve in
for sufficient
ster and do not remain evenly distributed in the vehicle
long time to ensure uniformity of dose. The examples of some of the

indiffusible solids are given in Table 9.2.

TABLE 9.2

Indiffusible Solids

Used Internally
Used Externally

Calamine Aspirin

Aromatic chalk powder

Hydrocortisone
Chalk
Sulphur precipitated

Phenobarbitone, sulphadimidine,
Zinc oxide
succinylsulphathiazole

(using compound tragacanth powder)

General method ofdispensing
all the ingredients.
(1) Finely powder
tragacanth
together in a mortar and add compound
(2) Mix them
powder.
to form a smooth
of the vehicle and
triturate
(5) Measure /,th
Cream. foreign
and, if it contains any
carefully
(4) Examine the suspension into a tared bottle.
a muslin piece
particles, strain through vehicleto clean
it.
of
quantity
(5) mortar with small
Rinse the
to the bottle.
Transfer the rinsings
(6) Add any liquid ingredient. volume.
the required
(7) the vehicle to produce
Add more of
194

DISPENSINGG
Example 9.3 Prepare and dispense the PHARMACY
following
suspension.
Bismuth carbonate
1.0
Prepared chalk
1.0
Kaolin
Tincture catechu
4.0 g
2.0 ml
Water add upto 30.0 ml
Prepare a mixture.
Send 4 doses.
Direction : One dose to be taken three times a day.
Method :
Mix the weighed quantities of
bismuth carbonate.
chalk and kaolin. To this
incorporate calculated prepared
quantity of
powder of tragacanth and mix cOmpound
thoroughly. Measure /4th of water.
A
small amount of water and
triturate to form a smooth
cream. Addthe
remaining portion of water.
Strain through muslin piece.
catechu in the centre of cream Add tincture
with continuous trituration. Add
moreof
water to produce the required volume.
Transfer the
suspension into
bottle, label and dispense.

Example 9.4 Prepare and dispense the following

suspension.

Succinyl sulphathiazole, in powder 3.0 g

Light kaolin 1.8 g
Compound tragacanth powder 0.3 8
Syrup raspberry 6.0 ml
Benzoic acid solution 0.6 ml
Amaranth solution 0.3 ml
Chloroform water to produce 30.0 ml
Prepare a mixture.
Direction : One tablespoonful to be taken three times a day.

Method ;
Mix succinyl sulphathiazole with light kaolin in a morta.
Add compóund powder of tragacanth. Add and triturate
syrup raspberry with
So as to form a smooth cream. Remove the
foreign particles if any
the tip of glass rod. Incorporate benzoic acid and amaranth
solution
SO as
solution previously diluted with chloroform water. Stirthoroughly
to form a uniform mixture. Add more of chloroform water to produce

the required volume. Transfer it into a bottle, labe! and dispense.

(3) Suspensions Containing Precipitate-Forming Liquids

addition
There are on
certain liquid preparationsthat is precipitated
and
tincture
to water. For [Link], compound benzoin tincture, myrrh
 BIPHASIC LIQUID DOSAGE FORM-SUSPENSIONS 195
Ch-9

tolu tincture. These liquids are not only insoluble in water but they form
indiffusible precipitates particularly when salts are present. They con
tain resinous matter and when it is mixed with water, it leads to

precipitationof resin and may stick to the sides of the bottle which will
be difficult to rediffuse by shaking. To prevent this, a protective colloid
isdispersed in the vehicle before tincture is added. Tragacanth mucilage
(1/4th of the total volume) or compound tragacanth powder (2 g/100 ml)
is commonly used as protective colloid.

General method of dispensing (using compound tragacanth powder)

(1) Finely powder the indiffusible solid and diffusible solid in the
mortar. Mix them with compound tragacanth powder in a
mortar.

(2) Measure half of the vehicle and incorporate a small anmount of it

to the powders with trituration until a snooth cream is formed.

Then add the remaining part of the vehicle.

(3) Measure the precipitate forming liquid in a dry measure and add
it in a slow stream in the centre of the cream with rapid stirring.

(4) Dissolve the soluble ingredient (if present) in sufficient amount

of vehicle out of the remaining half of the vehicle. Add it
avoid local high
slowly with constant stirring to the cream to
concentrations that may neutralise the effect of suspending
agent.

contents of the mortar critically for foreign parti

(5) Examine the
through muslin
cles. If these are present, strain the suspension
piece into a bottle.

to rinse the mortar and transferring the

(6) Add more of vehicle

rinsing to the bottle.

(7) Add any liquid ingredient.

produce the required volume.
(8) Add more of the vehicle to

General method of dispensing (using tragacanth mucilage)

Iragacanth mucilage is used
when the vehicle is water or chloroform
water.

with an equal volume

of the vehicle.
() Mix the tragacanth mucilage
in a dry measure and
(2) Measure the precipitate-forming liquid stirring.
of the mucilage with constant
pour slowly into the centre
if any, in about
/th of the vehicle
(5) Dissolve the solid substance
above mixture.
196 DISPENSING
PHARMACY
8 are same as that of general method
Step 5, 6, 7 and of

for preparing suspension containing precipitate forming dispensing

liquids
using
compound tragacanth powder.

Example 9.5 Prepare and dispense the following suspension,

B
Potassium jodide 2.0
Tincture of lobelia ether 8.0 ml
Tincture of stramonium 16.0 ml
Chloroform water add upto 90.0 ml
Prepare a mixture.
Direction

Method
:
:
One desert spoonful to be taken 4 times a day.

Mix the tragacanth mucilage with an equal volume f

chloroform water. Measure the calculated quantity of tincture of lobelia
ether and tincture of stramonium in a dry measure and
pour slowly into
the centre of the mucilage with continuous stirring.
Dissolve the potas

sium iodide in about /ath of the chloroform water and mix it with above
mixture, strain íf necessary, through muslin piece. Add more of chloro
form water to produce the final volume. Transfer to a bottle, label and
dispense.

(4) Suspensions Produced by Chemical Reactions

In this type of preparation of suspensions, the highly diluted solu
tions of reactants are mixed together so as to form very finely divided
precipitates that can be easily distributed throughout the liquid by shak
ing. The precipitates so formed are diffusible in nature.
Hence, there is

no need of adding any suspending

agent.

Example 8.6 Prepare and dispense the

following suspension.
R
Sulphurated potash 5.0 g
Zinc sulphate
5.0 g
Concentrated camphor water 2.5 ml
Water add upto 100.0 ml
Make a mixture.
Direction:To be used as
directed.
Method
(1) Dissolve the
sulphurated potash and zinc sulphate separately
in small quantity of vehicle.
(2) Add the zinc
sulphurated potash solution slowly to the
sulphate solution with
constant stirring.
 197
LIQUID DOSAGE FORMSUSPENSIONS
BIPHASIC
Ch-9
to a tared bottle.
(3) Transfer
camphor water with vigorous shaking
to redissolve
(4) Add
precipitated camphor.
volume.
(5) Mi itwell and make up the
in containers which are
Containers Suspensions should be packed
air space above the liquid
to permit adequate shaking.
adequate to permit
having in wide mouth bottles
oral suspensions should be packed
The
of the suspension.
removal
prompt
suspension must be labelled
Labelling Thecontainers having liquid
"Shake well before use". In case of dry suspen-
label
a secondary may be
with of vehicle to be mixed
sion powders, the specified amount
clearly on
the label.
indicated
should
be stored in a cool place but
Storage Suspensions should
temperatures should
Freezing at a very low
not be kept in a refrigerator.
suspended particles.
lead to aggregation of the
be avoided which may

STABILITY OF SUSPENSIONS
homogeneously with moderate
A suspension can be redisperse
stable The most
throughout its shelf
life.

and can be easily poured

flocculated i.e., the suspended
shaking
pharmaceutical suspensions are
stable semi-rigid
to form a loose,
together physically
particles are bonded to uphold each other while
suspended particles are said
structure. The particles of a
force on the liquid. The sedimented
exerting no significant any time with only
can be redispense easily at
flocculated suspension
moderate shaking.
by decreasing
can be made stable
The non-flocculated suspensions density
or by increasing the
size of the suspended material
the particle
and viscosity of the vehicle.

of suspensions
Evaluation of the stability
the physi
commonly used for evaluating
are
The following methods
cal stability of suspension: of sedimnentation
: The measurement
I. Sedimentation method of the stability
in the evaluation
volume is the most important parameter volume of the
by keeping a measured
determined a for
It is position
SuSpensions.
in an undisturbed (Hu) of the
Suspension in a graduated cylinder height
noted the ultimate
definite period of time and The sedimentation
the total suspension.
sediment and initial height of height(Hu/Ho).
height and
initial

volume F is the ratio of the ultimate

 198
DISPENSING
PHARMACY
The sedimentation volume can be plotted against time. The
indicates the sedimentation pattern suspension on storage.
of gragk
A
suspension shows a horizontal or less steep curve. The stable
evaluation of
redispersibility can also be deternined by shaking the
again find out the sedimentation volume (HuHo). suspension and

Rheological method
2.
at different
:
The viscosity of the suspension is
time intervals by using a good studied
quality of viscometer
provides useful information about the
stability of suspension.
3. Electrokinetic method
charge or zeta potential of
:
The determination of surface electrie
suspension is helpful to find out the stability
of suspension. Certain zeta
potentials produce more stable suspensions
because of controlled
flocculation. Zeta potential can be
calculated from
the migration velocities of
the particles measured by the
method. electrophoretic

on the
4. Micromeritic method :
The stability of a suspension
depends
size of the dispense phase.
particle
The size of the particle in a
suspension may grow and may
ultimatelylead to the formation
or caking. So any of lumps
change in particle size with
reference to time will
provide useful information
regarding the stability of a
change in particle size suspension. A
distribution and crystal habit may be
microscopy and coulter counter studied by
method.

MARKETED BIPHASIC LIQUID DOSAGE

(A) FORMS
Suspensions
1. Septran
suspension (Burroughs
Wellcome India) : Each 5 ml
contains Trimethoprim 40
mg, Sulphamethoxazole
200 mg.
2. Ciplin suspension
40 mg, (Cipla): Each 5 ml contains
Sulphamethoxazole 200 mg. Trimethoprin

3. Mebex suspension
100 mg. (Cipla): Each 5 ml contains MebendazOle

4. Enterocin suspension
Chloramphenicol sodium
(Alpine
Industries)
succinate 125 mg.
: Each 5 ml contains

5.
Dependal-M suspension
lidone 25 mg, (Eskayef)
Metronidazole 75 mg.
: Each 5 ml contains Furazo-

tains
6. Campicilin
suspension (Cadila
Ampicillin anhydrous
7. Chlorambin
100 mg.
Health :
Care) Each 5 ml con-

Light Kaolin
suspension
1 g. Pectin
(ACELaboratories)
50 g,
Neomycin
: Each 5 ml contains

50 mg.
sulphate