Brief introduction and definition

Advantages

Types

Classification on different basis

Criterias for suspensions

Evaluation of suspension

Formulation of suspension

Preparation techniques

Comparison of flocculated and deflocculated

A system in which one substance (The

Dispersed Phase) is distributed, in discrete

units, throughout a second substance (the

continuous Phase).

Coarse dispersions are of 2 types:

1-Suspensions

2-Emulsions

Suspensions are heterogeneous biphasic

thermodynamically unstable coarse

dispersion system in which internal phase

is dispersed uniformly throughout the

external phase with the aid of single or

combination of suspending agents.

particle size of internal phase ranges

between 10 – 15 micrometer.

For example, Paracetamol suspension,

insulin zinc suspension.

To increase solubility of insoluble drug

To mask bitter taste of drug e.g

chloramphenicol palmitate

To increase drug chemical stability e.g.

Procaine penicillin G

To achieve controlled/sustained drug

release.

They exhibit higher rate of bioavailability

than capsule and tablets.

1- Antacid oral suspension

• e.g chloramphenicol palmitate suspension

2- Antibacterial oral suspension

• e.g ciprofloxacin suspension

3- Dry powder for oral suspension

• e.g. zithromax powder for oral suspension

4- Analgesic oral suspension

• e.g. ibuprofen suspension

5- Anthelmentic suspension

e.g mintezol oral suspension

6- Anticonvulsant oral suspension

• e.g. phenytoin suspension

7- Antifungal oral suspension

• e.g nystatin suspension

8- Antidiarrheal oral suspensions

• e.g bismuth subsalicylates suspension

9- Parenteral suspensions

• e.g Procaine penicillin G Insulin Zinc

Suspension

10- Opthalmic suspensions

• e.g. betoptic S (betaxolol hydrochloride

ophthalmic suspension)

11- Suspension for external use

• e.g.Calamine lotion.

12- Vaccines

• e.g. Cholera vaccine

13- X-ray contrast agent

• e.g. Barium sulphate for examination of

alimentary tract

Suspensions can be classified on the basis of:

Mode of dispensing

Concentration

Particle size

Sediments

There are 2 types of suspensions:

Extemporaneous suspensions

Reconstituted suspensions

Such suspensions are prepared just before

dispensing to the patients;

• who are unable to swallow solid dosage

forms ( tablet and capsules) e.g. infants

• When no other liquid dosage form is

available.

USP designs these suspensions as

“ORAL SUSPENSIONS”

They have high specificity regarding addition

of suspending agent, storage and labeling.

For example: Pediatric antibiotic

suspensions , rifadin suspensions

These are powders or granules which are

intended to be suspended in water or some

other vehicle prior to oral administration

In USP these are designated as:

“FOR ORAL SUSPENSION”

For example:

• tetracycline suspension and barium sulphate

for oral suspension.

There are 2 types of suspensions:

• Dilute suspensions

• Concentrated suspensions

“ Such suspensions in which

concentration of solid particles ranges from 2

to 10% w/v solid”

For example: cortisone acetate suspension,

prednisolone acetate suspension.

“Such suspensions in which

concentration of solid particles is 50%w/v”

For example:

• zinc oxide suspension

There are 3 types of suspensions:

Colloidal suspensions

Coarse suspensions

Nano suspensions

COLLOIDAL SUSPENSIONS

• Suspensions having particle size of dispersed solid less than about 1 micron

COARSE SUSPENSIONS

• Suspensions having particle size of dispersed phase greater than 1 micron

NANO SUSPENSIONS

• These suspensions are biphasic colloidal dispersions of nano sized drug particles stabilized by surfactants. Size of dispersed phase is less than 1 micrometre.

On the basis of sedimentation, there are 2

types of suspensions:

• Flocculated suspensions

• Deflocculated suspensions

In these suspensions, there is a formation of

light, fluffy group of particles held together

by weak vander waals forces.

In these suspensions, solids are present as

individual particles, they exhibit aggregation

but comparatively low than flocculated

suspensions.

A well-formulated suspension should have:

Easy and readily redispersion of sedimented

particles , important for uniformity of dose

No cake formation on setting

Viscosity optimum for pouring

Physical, chemical and microbiological

stability

Pleasing odor, colour and palatability

Free from gritting particles( in case of

suspensions for external use)

Proper sterility in case of ophthalmic and

parentral suspensions

Suspensions are evaluated by determining their

physical stability, methods inlude:

Sedimentation method

Rheological method

Electro kinetic method

Micromeritic method

Sedimentation of particles in a suspension is

governed by several factors:

• particle size

• density of the particles

• density of the vehicle

• viscosity of the vehicle

The velocity of sedimentation of particles in

a suspension can be determined by using the

Stoke's law.

Where:

v = velocity of sedimentation

d = diameter of the particle

g = acceleration of gravity

p1 = density of the particle

p2 = density of the vehicle

η = viscosity of disperse medium in poise

v =d2 (p1-p2) g

18 v =

d2 (p1-p2) g

18

Two parameters are studied for

determination of sedimentation

Sedimentation volume

Degree of flocculation

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

F has values ranging from less than one to

greater than one

• When F < 1 Vu < Vo

• When F =1 Vu = Vo

• 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

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∞

• F =(Vu/Vo) deflocculated

• F∞ = Vu/Vo) deflocculated

The minimum value of ß is 1,when

flocculated suspension sedimentation volume

is equal to the sedimentation volume of

deflocculated suspension.

Solid particles can get charged by:

• Selective adsoption of ions at surface

• Ionization of functional group of dispersed

phase

Two type of electrical potential cotribute to

electrokinetic properties of suspensions:

Nernst potential

Zeta Potential

The flocculated suspension is one in which

zeta potential of particle is -20 to +20 mV.

• The difference in electric potential between the actual surface of the particle and the electroneutral region is referred to as Nernst potential.

Nernst 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.

Zeta Potential

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-

- -

--

--

-

-

-

-

- - -

- -

-

-

a-

a

b-

b

c-

c

d-

d

Tightly

bound

layer

Diffusion

layer

Electro-neutral

region

Surface

Counterion Shear plan

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--

-- --

----

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--

--

--

--

-- -- --

-- --

--

--

a-

a

b-

b

c-

c

d-

d

Tightly

bound

layer

Diffusion

layer

Electro-neutral

region

Surface

Counterion Shear plan

phenomenon of flocculation.

………

Attractive forces exceed the repulsive forces

If the zeta potential is reduced below a certain value

phenomenon of deflocculation.

………

Repulsive forces supersede the attractive forces

If the zeta potential is higher than the critical value

The viscosity of the suspension is studied at

different time intervals by using a good

quality of viscometer, it gives useful

information about the stability of suspensions

Stability of suspension depends upon the

particle size of the dispersed phase

Any change in particle size with reference to

time will provide useful information

regarding the stability of a suspension

Three approaches are commonly involved:

Use of structured vehicle

Use of controlled flocculation

Combination of both of the methods

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

Entrapped the particle and reduces the

sedimentation of particles.

E.g. methyl cellulose,sodium carboxy methyl

cellulose, acacia, gelatin and tragacanth

Controlled flocculation of particles is

obtained by adding flocculating agents,

which are:

electrolytes ( bismuth subnitrate, monobasic

pot. Phosphate)

surfactants (ionic and nonionic)

polymers

Sometimes suspending agents can be added

to flocculated suspension to retard

sedimentation

Examples of these agents are:

Carboxymethylcellulose (CMC),

Carbopol 934,

Veegum, and bentonite

Work by increasing viscosity of liquid

vehicle, and slowing down settling in

accordance to Stokes Law, these agents

mainly prevents caking at the base of any

suspentions. Suspending agent form film

around particle and decrease interparticle

attraction.

Most suspending agents perform two

functions

• besides acting as a suspending agent

• they also imparts viscosity to the solution

SUSPENSIONS

Suspending agents Stability pH

range

Concentrations 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

methylcellulose

3-11 1-2%

CMC 7-9 1-2%

Colloidal

silicon dioxide

0-7.5 2- 4 %

Stability pH range and concentrations of most commonly used suspending agents.

52

Commonly used suspending agents include

• Alginates

• Methylcellulose

• Hydroxyethylcellulose

• Carboxymethylcellulose

• Sodium Carboxymethylcellulose

• Microcrystalline cellulose

• Acacia

• Tragacanth

• Xantham gum

• Bentonite

• Carbomer

• Carrageen

• Powdered cellulose

• Gelatin

Two main formation methods are used:

Precipitation methods:

Dispersion method:

Three main methods

Organic solvent precipitation

Precipitation effected by changing pH of the

medium

Double decomposition

Water insoluble drugs

Dissolve in organic solvents

Add organic phase to water

organic solvents include ethanol, methanol,

propylene glycol and polyethylene glycol.

Applicable to those drugs in which solubility

is dependent on pH value.

Concentrated solution in favorable pH

pour to other system to change pH

On agitation precipitate will form

E.g estradiol suspension.

Two water soluble reagent forms a water

insoluble product.

Eg white lotion NF

Zinc sulphate solution

Solution of sulphurated potash

Precipitate of zinc polysulphide

Vehicle is formulated

solid phase is wetted and dispersed

use of surfactant to ensure wetting of

hydrophobic solids

Small scale preparation of suspensions

Large scale preparation of suspensions

Grinding the insoluble materials with a vehicle

containing the wetting agent.

soluble ingredients are dissolved in same

portion of the vehicle

Added to the smooth paste to step1 to get

slurry.

Make up the dispersion to the final volume

If suspension is made by dispersion process it

is best to achieve pulverization of solid by

micronization technique or spray drying

If suspension is made by controlled

crystallization, a supersaturated solution

should be formed and then quickly cooled

with rapid stirring.

Floculated suspension Defloculated suspension

Particles forms loose aggregates and form flock

Rate of sedimentation is high

Particles exist as separate entities form a cake

Rate of sedimentation is slow

Floculated defloculated

Sediment is rapidly formed

Sediment is loosely packed and doesn’t form a hard cake

Sediment is easy to re disperse

Suspension is not pleasing in appearance

The floccules stick to the sides of the bottle

Supernatant formed is clear

Sediment is slowly formed

Sediment is very closely packed and a hard cake is formed

Sediment is difficult to re disperse

Suspension is pleasing in appearance

They don’t stick to the sides of the bottle

Cloudy supernatant

Floculated defloculated

Sediment is rapidly formed

Sediment is loosely packed and doesn’t form a hard cake

Sediment is easy to re disperse

Suspension is not pleasing in appearance

The floccules stick to the sides of the bottle

Supernatant formed is clear

Sediment is slowly formed

Sediment is very closely packed and a hard cake is formed

Sediment is difficult to re disperse

Suspension is pleasing in appearance

They don’t stick to the sides of the bottle

Cloudy supernatant