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Suspension

Suspensions are heterogeneous liquid dosage forms with insoluble solid particles uniformly distributed in a liquid phase, classified by their application, solid particle proportion, size, and electrokinetic properties. Flocculated suspensions have higher sedimentation rates and easier re-dispersal compared to deflocculated suspensions, which settle slowly and can form hard cakes. Key components in suspensions include suspending agents, wetting agents, and thickeners, and they are evaluated for stability through methods like sedimentation and rheological assessments.

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0% found this document useful (0 votes)
10 views

Suspension

Suspensions are heterogeneous liquid dosage forms with insoluble solid particles uniformly distributed in a liquid phase, classified by their application, solid particle proportion, size, and electrokinetic properties. Flocculated suspensions have higher sedimentation rates and easier re-dispersal compared to deflocculated suspensions, which settle slowly and can form hard cakes. Key components in suspensions include suspending agents, wetting agents, and thickeners, and they are evaluated for stability through methods like sedimentation and rheological assessments.

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rd279670
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Definition:

Suspension are heterogeneous, biphasic liquids dosage form in which


insoluble solid particulate (internal or dispersed phase) are uniformly
distributed in liquid phase (external phase or dispersion medium), which
may be stabilized by inclusion of suspending agents.
Classification:
1. Based on General Classes:
a) Oral Suspension (Ex. Paracetamol suspension, antacids)
b) Externally applied Suspension (Ex. Calamine lotion)
c) Parenteral Suspension (Ex. Insulin Zinc Suspension)
2. Based on proportion of solid particles:
a) Dilute suspension (2 to 10% w/v solid)
Ex. Cortisone Acetate
b) Concentrated suspension (50% w/v solid)
Ex. Zinc oxide suspension
3.Based on Size of Solid Particles:
a) Colloidal suspension (< 1 micron)
b) Coarse suspension (>1 micron)
c) Nano suspension (<1 𝜇m)
4.Based on Electro kinetic Nature of Solid Particles:
a) Flocculated suspension
b) Deflocculated suspension
.

Flocculated Suspension
De-flocculated Suspension
o Particles forms a loose aggregate o Particles exist as separate entities.
& form network like structure.
o Rate of sedimentation is high. o Rate of sedimentation is slow.
o Sediment is easy to re-disperse. o Sediment is difficult to re-disperse.
o Sediment is loosely packed &
does not form hard cake. o Sediment is very closely packed &
o Supernatant liquid is clear. formed hard cake.
o Floccules stick to the side of
bottle. o Supernatant liquid is not clear.
o Suspension is not pleasing in o Nothing stick to the side of bottle
appearance.
o Suspension is pleasing in appearance.
Flocs

Flocculated Suspensions:
 In flocculated suspension, formed flocs (loose aggregates) will cause increase in

sedimentation rate due to increase in size of sedimenting particles.


 Hence, flocculated suspensions sediment more rapidly.
 Here, the sedimentation depends not only on the size of the flocs but also on the
porosity of flocs.
Deflocculated Suspensions:
 In deflocculated suspension, individual particles are settling.
 Rate of sedimentation is slow, which prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.
Hard Cake
 This phenomenon called ‘caking’ or ‘claying’.
 In deflocculated suspension larger particles settle fast and smaller remain in

supernatant liquid so supernatant appears cloudy.


Property Solution Colloid Suspension

Particle Size Less than1 nm 1 to 100 nm More than 100 nm

Appearance Clear Cloudy Cloudy

Separation Does not separate Does not separate Separates or Settles

Filterability Passes through the Passes through the Particles do not passes through
filter paper filter paper the filter paper

Effect of beam of light Light can pass Scatters light Light can not pass

Example Sugar Solution, Milk, paints Mixture of chalk and water,


Powdered drink mixture of flour and water
 In ideal suspension, suspended particles
should not settle rapidly and sediment
produced, must be easily re-suspended by
the use of moderate amount of shaking.
 It should be easy to pour yet not watery and
no grittiness.
FEATURES OF  It should have pleasing odor , colour and
PHARMACEUTICAL palatability.
SUSPENSION:  Good syringeability.
 It should be physically, chemically and
microbiologically stable.
 Parenteral and Ophthalmic suspension should
be sterilizable.
1. Sedimentation
2. Brownian movement
3. Electokinetic
1. Theory of Sedimentation:
Sedimentation means settling of particle (or) floccules occur under gravitational force in liquid
dosage form.
Velocity of sedimentation expressed by Stoke’s equation:
Stoke's equation only may be applicable when:

Spherical particles in a
very dilute suspension
(0.5 to 2 gm per 100 mL).

Particles which freely Particles with no


settle without collision physical or chemical
. attraction.
 Brownian movement of particle prevents
sedimentation by keeping the dispersed material in
random motion.
 Brownian movement depends on the density of
dispersed phase and the density and viscosity of
the disperse medium.
 The kinetic bombardment of the particle by the
molecules of the suspending medium will keep the
particles suspending, provides that their size is
below critical radius (r).
Brownian movement can be observed:
 If particle size is about 2 to 5mm.
 When the density of particle & viscosity of medium
are favourable.
Physical Stability can be achieved by
maintaining the particle in Brownian motion
as:
a) Provide Electric charge on surface of
dispersed particle:
The like charge on the particles will
prevent these coming closer together and
thus maintaining a Brownian motion.
b) Maintain solvent sheath around the
particle:
The solvent layer prevent the particle
coming closer and also maintain Brownian
motion.
3. ELECTRO KINETIC PROPERTIES:
Zeta 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 has practical application in
stability of systems containing dispersed
particles .
 If the zeta potential is reduced below a certain
value, the attractive forces exceed the repulsive
forces, and the particles come together. This
phenomenon is known as flocculation.
 The flocculated suspension is one in which zeta
potential of particle is -20 to +20 mV.
 Thus the phenomenon of flocculation and de
flocculation depends on zeta potential carried by
particles.
Suspending Wetting Flocculating Thickeners
agents agents agents

Buffers and
Osmotic Coloring Preservatives
pH adjusting
agents agents
agents

External
liquid vehicle
Suspending agents:
 Suspending agent are also known as
hydrophilic colloids which form colloidal
dispersion with Water and increase the
viscosity of the continuous phase.
 Suspending agent form film around
particle and decrease interparticle
attraction.
 Most suspending agents perform two
functions i.e. besides acting as a
suspending agent they also imparts
viscosity to the solution.
 Ex.: Methylcellulose, tragacanth,
hydroxyethylcellulose, acacia etc.
Wetting agents (Surfactants):
 They help reduce surface tension to improve the
wetting and dispersion of hydrophobic ingredients.
The main types used are
 Anionic Surfactants: These are carrying a negative
charge. Example: Sodium lauryl sulfate, which
helps in cleaning and foaming.
1.Cationic Surfactants: These have a positive charge
and are often used because they can kill bacteria,
acting as preservatives. Example: Benzalkonium
chloride, commonly found in throat lozenges.
2.Amphoteric Surfactants: These surfactants can act
as either positive or negative, depending on the
situation. Example: Betaines, used in shampoos and
conditioners.
3.Non-Ionic Surfactants: These don't carry any charge
and are fantastic at making drugs dissolve better and
remain stable in a solution. Example: Polysorbates,
often used in eye drops and vaccines.
If the material is more hydrophilic less difficulty in
wetting by water.
 Surfactants decrease the interfacial tension
between drug particles and liquid thus liquid is
penetrated in the pores of drug particle displacing
air from them and thus ensures wetting.
.  Generally, we use non-ionic surfactants but
ionic surfactants can also be used depending upon
certain conditions.
 Ex.: Polysorbate 80
 Polysorbate 80 is most widely used due to its
advantages like non toxicity and non ionic
property (stable in pH of medium).
 Flocculating agents:
 They are added to floc the drug particles
 Dispersion can be improved by adding a
surfactant or protective colloid which acts as
flocculating agent.
 The flocculating agent acts by reducing the
surface tension and thereby improving the
dispersion of solids and minimize flocculation.
.  Ex.: sodium lauryl sulphate (SLS), carbowaxes
and electrolytes.
 Thickeners:
 They are added to increase the viscosity of
suspension.
 Ex.: Gum acacia, Tragacanth, Starch, Sodium
alginate etc.
 Buffers and pH adjusting
agents:
 They are added to stabilize the
suspension to a desired pH range or
resist any change in pH when an acid or
base is added.
 To encounter stability problems all
liquid formulation should be formulated
to an optimum pH.
 Rheology, viscosity and other property
are also dependent on the pH of the
system.
 Generally pH of suspension preferably
at 7.4-8.4.
 Most commonly used buffers are salts of
weak acids such as carbonates,
citrates etc.
 Osmotic agents:
 They are added to produce osmotic pressure comparable
to biological fluids when suspension is to be intended for
ophthalmic or injectable preparation.
 Ex.: mannitol, sorbitol, NaCl etc.
 Coloring agents:
 They are added to impart desired color to suspension and
improve elegance.
 Colors are obtained from natural or synthetic sources used
as coloring agents.
 Plant colors are most widely used for oral suspension.
 The synthetic dyes should be used within range of( 0.0005
% to 0.001%)
 Color aids in formulation for the identification of the
product and the color used should be acceptable by the
country.
 Ex.: Indigo carmine gives blue colour, amaranth gives
red colour etc.
 Preservatives:
 Preservatives are added to prevent microbial growth.
 Ex.: Benzoic acid (0.1% in concentration), Butyl
paraben 0.006-0.05% in oral suspension and 0.02-
0.4% in topical formulation.
 External liquid vehicle:
 They are added to construct structure of the final
suspension.
 Sweetening agents:
 They are used for taste masking of bitter drug
particles.
 Ex.: glucose, mannose, Sorbitol, sodium saccharin
etc.
 Bulk sweeteners is used at concentration of 15-70 %
It absorb moisture and
prevent degradation of
API by moisture.

Ex.: propylene glycol,


Humectants:
.
glycerol.

Total quantity of
humectants should be
between 0-10 % w/w.
 Step1: Grind or levigate the insoluble materials with

the help of mortar to a smooth paste with adding a


vehicle containing the wetting agent.

Step 2: All soluble ingredients are dissolved in same

portion of the vehicle and added to the above prepared


smooth paste to get slurry.
 Step 3: Then the slurry is transformed to a graduated cylinder and

the mortar is rinsed with successive portion of the vehicle.

 Step 4: Decide whether the solids are suspended in a structured

vehicle/ Flocculated and then suspended by adding the vehicle


containing the suspending agent (or) flocculating agent.

 Step 5: Make up the dispersion to the final volume via adding the

external liquid vehicle. Thus suspension is prepared.


Step1: Grind or levigate the insoluble materials with the help of mortar to a smooth paste with
adding a vehicle containing the wetting agent.

Step 2: All soluble ingredients are dissolved in same portion of the vehicle and added to the
above prepared smooth paste to get slurry.

Step 3: Then the slurry is transformed to a graduated cylinder and the mortar is rinsed with
successive portion of the vehicle.

Step 4: Decide whether the solids are suspended in a structured vehicle/ Flocculated and then
suspended by adding the vehicle containing the suspending agent (or) flocculating agent.

Step 5: Make up the dispersion to the final volume via adding the external liquid vehicle. Thus
suspension is prepared.
Sedimentation method.

Rheological method.
EVALUATION OF
SUSPENSIONS:
Electro kinetic method.

Micromeritic method.
Sedimentation method:
There are two parameters
are studied for
determination of
sedimentation:
1. Sedimentation volume.
2. Degree of flocculation.
 The sedimentation method is a common technique used
to evaluate the stability of pharmaceutical suspensions.
Here are the key parameters and steps involved:

 1. Sedimentation Volume (F): This is the ratio of the


ultimate volume of sediment (Vu) to the original volume
of the suspension (Vo). It helps determine the degree of
flocculation.
 2. Degree of Flocculation (β): This is the ratio of the
sedimentation volume of the flocculated suspension (F)
to the sedimentation volume of the deflocculated
suspension (F∞).

Rheological method:
 It provide the information about settling
behaviors of particulates.
 Brookfield viscometer is used to study the
viscosity of the suspension.
 This technique also indicates at which level
of the suspension the structure is greater
owing to particle agglomeration.
 The dial reading is plotted against the
number of turns of the spindle. The better
suspension show a lesser rate of increase of
dial reading with spindle turns, i.e. the
curve is horizontal for long period.
Electro kinetic method:
 Measurement of Zeta-potential can be performed using Micro electrophoresis apparatus & Zeta Plus.

It shows the stability of a disperse system.

Micromeritic method:
 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 or coulter counter

method.

pH measurement:
 The measurement and maintenance pH is also very important step in the Quality control testing
Improve chemical stability of
certain drug e.g. Procaine
penicillin G.
Higher rate of bioavailability
than capsules and tablets.

ADVANTAGES:
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.
Physical stability , sedimentation
and compaction can causes
problems.

It is bulky sufficient so care must


be taken during handling and
transport.
DISADVANTAGES:
It is difficult to formulate.

Uniform and accurate dose can not


be achieved unless suspension are
packed in unit dosage form.
 Suspension is usually applicable for drug which is
insoluble (or ) poorly soluble in nature. Ex.:
Prednisolone suspension
 To prevent degradation of drug or to improve stability
of drug. Ex. Oxytetracycline suspension.
 To mask the taste of bitter of unpleasant drug. Ex.:
Chloramphenicol palmitate suspension.
 Suspension of drug can be formulated for topical
APPLICATION: application. Ex.: Calamine lotion.
 Suspension can be formulated for parenteral application
in order to control rate of drug absorption. Ex.:
penicillin procaine
 Vaccines as a immunizing agent are often formulated as
suspension. Ex. Cholera vaccine.
 X-ray contrast agent are also formulated as suspension.
Ex.: Barium sulphate for examination of alimentary tract.
NANO TASTE MASKED
SUSPENSIONS. PHARMACEUTICAL
ADVANCEMENT IN SUSPENSIONS.

THE FIELD OF
SUSPENSION:

SUSTAINED RELEASE
SUSPENSIONS.

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