SUSPENSION

A pharmaceutical suspension may be defined as a coarse dispersion containing finely divided

insoluble material suspended in a liquid medium.

The physical chemist defines the word “suspension” as two-phase system consisting of an
undissloved or immiscible material dispersed in a vehicle (solid, liquid, or gas).

ROUTES OF ADMINISTRATION OF SUSPENSION

Suspensions are used for the application of dermatological materials to the skin and mucous
membrane and for parenteral usage. Thus suspensions can be administered by oral, topical,
parenteral and ophthalmic application.

ORAL SUSPENSIONS
Patients who have problems in swallowing solid dosage forms require drugs to be dispersed in
a liquid. Oral suspensions permit the formulation of poorly soluble drugs in the form of liquid
dosage form. As these suspensions are to be taken by oral route therefore they must contain
suitable flavoring and sweetening agents. Drugs, which possess unpleasant taste in solution
dosage form like paracetamol, chloramphenicol palmitate etc. can be formulated as palatable
suspension as they are suitable for administration to peadiatric patients. Finely divided solids
like kaolin, magnesium carbonate etc., when administered in the form of suspensions will be
available to a higher surface area for adsorptive and neutralizing actions in the gastrointestinal
tract.

TOPICAL SUSPENSIONS
These suspensions are meant for external application and therefore should be free from gritty
particles. There consistency may range from fluid to paste. Example of fluid suspension
includes calamine lotion, which leave a deposit of calamine on the skin after evaporation of the
aqueous dispersion phase. Zinc cream has a consistency of semisolid. Zinc cream consists of
high percentage of powders dispersed in an oily (paraffin) phase.

PARENTERAL SUSPENSIONS
These suspensions should be sterile and should possess property of syringability. Parenteral
suspensions are also used to control the rate of absorption. As the absorption rate of the drug
is dependent on the dissolution rate of the solid. Therefore by varying the size of the dispersed
solid particles the duration and absorption can be controlled. Vaccines are also formulated as
dispersions of killed microorganisms for example in Cholera vaccine or as toxoid adsorbed on
to substrate like aluminium hydroxide or phosphate for prolonged antigenic stimulus. For
example adsorbed Diphtheria and Tetanus toxoid.

OPHTHALMIC SUSPENSIONS
These should also be sterile and should possess very fine particles. Drugs, which are unstable
in aqueous solution, are formulated as stable suspensions using non-aqueous solvents. For
example fractioned coconut oil is used for dispersing tetracycline hydrochloride for ophthalmic
use.

PROPERTIES OF SUSPENSION
 Desirable properties of suspensions.

1 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
  Suspensions should possess good pourability leading to ease of removal of dose from
container.
 They should have good organoleptic properties.
 The particle size distribution should be uniform.
 There should be ease of redispersion of settled solid particles.
 They should be physically and chemically stable.
 They should be resistant against microbial contamination.

THEORIES INVOLVED IN DISPERSE PHASE

Interfacial phenomenon
Smaller solid particles are used to disperse in a continuous medium. Smaller particle size and
large surface area is associated with a surface free energy making it thermodynamically
unstable. Thus the particles possess high energy which leads to grouping together to reduce
surface free energy thus leading to formation of floccules. These floccules are held together
among themselves and within by weak van der waals forces. However in cases where
particles are adhered by stronger forces to form aggregates forming hard cake. These
phenomena occur in order to make system more thermodynamically stable. In order to
achieve a state of stability the system tend to reduce the surface free energy, which may be
accomplished by reduction of interfacial tension that is achieved by use of surfactants.

Electrical Double layer and Zeta potential

Most surfaces acquire a surface electric charge when they come in contact with aqueous
surface. A solid charged surface when in contact with an aqueous medium possesses positive
and negative ions. The counter ions are attracted towards the surface co-ions that ions of like
charge are repelled away from the surface. This results in the formation of an electrical double
layer, made up of the charged particles. The charges influence the distribution of ions resulting
in the formation of an electrical double layer, made up of the charged surface and a
neutralizing excess of counter-ions over co-ions distributed in a diffuse manner in the aqueous
medium resulting into electric potentials. The zeta potential refers to the electrostatic charge
on the particles, which causes them to move in electric field towards a pole of opposite
charge. Its magnitude may be measured using micro electrophoresis or any other of the
electrokinetic phenomena. The two parts of the double layer are separated by a plane, the
stern plane. The stern plane, which occur at a hydrated ion radius from the particle surface.
The ions or molecules to be strongly adsorbed at the surface-termed specific adsorption rather
than by electrostatic attraction. The specifically adsorbed ion or molecule may be uncharged
e.g., with non-ionic surfactant. Surfactants specifically adsorb by the hydrophobic effect and
impart effect on the stern potential. Thus the zeta potential is reduced by additives to the
aqueous system in either (or both) of two different ways.

Sedimentation Concept
In dispersions the dispersed particles encounters between themselves as a result of Brownian
movement. Depending upon the forces of interactions-electrical forces of repulsion, forces of
attraction and forces arising due to solvation, the particles aggregate to form collection of
particles. The collisions result in permanent contact of particles known as coagulation leading
to the formation of larger aggregates, which sediment out known to exhibit flocculation or if the
particles rebound they remain freely suspended and form stable system. These particles
sediment according to stokes’ law.
According to Stokes’ law

2 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
v = 2a2g (σ-ρ)/9η
Where v is velocity of sedimentation, a is the radius of particles, σ density of solid particles, g
is acceleration due to gravity and ρ is the density and η is the viscosity of the dispersion
phase.
The equation of stokes’ law reflects that larger particles exhibit greater velocity of
sedimentation. The velocity of sedimentation is inversely proportional to the viscosity of
dispersion medium.

TYPES OF SUSPENSION
Suspensions are classified as:

According to the route of administration

 Oral suspensions should be taken by oral route and therefore must contain suitable flavoring
and sweetening agents.
 Topical suspensions meant for external application and therefore should be free from gritty
particles.
 Parenteral suspensions should be sterile and should possess property of syringability.
 Ophthalmic suspensions should be sterile and should possess very fine particles

According to nature of dispersed phase and methods of preparation

The suspensions are classified as suspensions containing diffusible solids, indiffusible solids,
poorly wettable solids, precipitate forming liquids and products of chemical reactions.

According to nature of sediment

Flocculated Suspensions: In this type the solid particles of dispersed phase aggregate leading
to network like structure of solid particles in dispersion medium. The aggregates form no hard
cake. These aggregates settle rapidly due to their size as rate of sedimentation is high and
sediment formed is loose and easily redispersible. The suspension is not elegant, as
dispersed phase tends to separate out from the dispersion medium. Therefore it is desired that
flocculation should be carried out in a controlled manner so that a balance exists between the
rate of sedimentation and nature of sediment formed and pourability of the suspension.
Non-flocculated Suspensions: In this type the solid particles exist as separate entities in
dispersion medium. The sediments form hard cake. The solid drug particles settle slowly as
rate of sedimentation is low. As sediments are formed eventually there is difficulty of
redispersion. The suspension is more elegant as dispersed phase remain suspended for a
long time giving uniform appearance.

FORMULATION OF SUSPENSION
Suspensions containing diffusible solids consist of solids insoluble in water but easily
wettable. On shaking with water solid particles diffuse readily through out the liquid and remain
suspended for a long time. The suspensions containing diffusible solids are prepared by
triturating the solids in a mortar with sufficient quantity of vehicle to form a smooth cream. Any
soluble nonvolatile substance is then added by separately dissolving them in a small quantity
of vehicle. More vehicles are then added and any foreign particle is strained through a muslin
cloth. Any volatile component is added at this stage and adding the required quantity of
vehicle makes up the final volume.

Example: Magnesium Trisilicate Mixture

3 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
 INGRADIENTS QUANTITY
Magnesium Trisilicate 5.0 gm
Light Magnesium Carbonate 5.0 gm
Sodium bicarbonate 5.0 gm
Concentrated Peppermint water 2.5 ml
Chloform water 50.0 ml
Purified water qs to 100 ml

Suspensions containing indiffusible solids consist of substances, which do not remain

distributed in the dispersion medium when shaken for long time to ensure uniformity of dose.
They are prepared by adding a suitable thickening agent to the vehicle, which increases the
viscosity of the vehicle and delays the separation or sedimentation of indiffusible particles.

Example: Calamine Lotion

INGRADIENTS QUANTITY
Calamine 15.0 gm
Zinc Oxide 5.0 gm
Bentonite 3.0 gm
Sodium Citrate 0.5 gm
Liquified Phenol 0.5 ml
Glycerine 5.0 ml
Purified water qs to 100 ml

Suspensions containing poorly wettable solids consist of substances, which are poorly
soluble, and at the same time poorly wetted by the dispersion medium, and clump together
with the difficulty to disperse. They are prepared by including suitable wetting agent in the
formulation. These agents get adsorbed at the solid/liquid interface and promote wetting of the
solid particles by the liquid of the dispersion medium.

Example: Sulphur Lotion

INGRADIENTS QUANTITY
Precipitated Sulphur 4.0 gm
Quillia Tincture 0.5 ml
Glycerin 0.2 ml
Alcohol (95%) 6.0 ml
Calcium Hydroxide Solution qs to 100 ml
Suspensions of precipitate forming liquids consist of liquid tinctures which are alcoholic or
hydroalcoholic extract of vegetable drugs which contain resinous material. When tinctures are
added to water they precipitate. Precipitates are indiffusible and stick to the walls of the
container. They are prepared by adding a suitable thickening agent prior to the addition of the
precipitate forming liquid.

4 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
 Example: Lobelia and Stramonium Mixture

INGRADIENTS QUANTITY
Lobelia Ethereal Tincture 16.0 ml
Tragacanth mucilage 40.0 ml
Potassium Iodide 4.0 gm
Chloroform water qs to 180 ml
Suspensions produced by chemical reactions are prepared by mixing two dilute solutions of
reactants to form a fine precipitate. Generally precipitates so formed are diffusible and no
suspending agent is required. If precipitate is indiffusible a suitable thickening or suspending
agent may be added. They are prepared by dissolving the reactants separately in
approximately half volumes of the vehicle and the two portions are then mixed together.

Example: Zinc Sulphide Lotion

INGRADIENTS QUANTITY
Zinc Sulphate 4.0 gm
Sulphurated Potash 4.0gm
Purified water qs to 100 ml

STABILITY OF SUSPENSIONS
The physical stability of a pharmaceutical suspension is the condition in which the particles do
not aggregate and in which they remain uniformly distributed throughout the dispersions. In
order to achieve this ideal situation the suspension should have additive, which are added to
achieve ease in resuspension by a moderate amount of agitation. Taking a case example: In
case of dispersion of positively charged particles that is flocculated by addition of an aninonic
electrolyte like monobasic potassium phosphate. The physical stability of the system is
enhanced by addition of carboxymethylcellulose, Carbopol 934, veegum, tragacanth or
bentonite either alone or in combination. No physical incompatibility is recorded as majority of
hydrophilic colloids are negatively charged and are compatible with anionic flocculating
agents. When a flocculated suspension of negatively charged particles with a cationic
electrolyte is prepared (aluminum chloride) the addition of hydrocolloid may result in an
incompatible product resulting in stingy mass, which has no suspending action, and settle
rapidly. In such a condition protective agent is added to change the sign on the particles from
the negative to positive is employed which can also be achieved by the adsorption onto the
particle surface by fatty acid amine or gelatin. Thus an anionic electrolyte is used to produce
floccules that are compatible with negatively charged suspending agent.

QUALITY CONTROL TEST FOR SUSPENSIONS

Sedimentation volume
Redispersibility is the major consideration in assessing the acceptability of a suspension. The
measurement of the sedimentation volume and its ease of redispersion form two of the most
common basic evaluative procedures. The sedimentation volume is the simple ratio of the
height of sediment to initial height of the initial suspension. The larger the value better is the
suspendability.

5 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
Particle size and size distribution
The freeze-thaw cycling technique used to assess suspension for stress testing for stability
testing result in increase of particle growth and may indicate future state after long storage. It
is of importance to study the changes for absolute particle size and particle size distribution. It
is performed by optical microscopy, sedimentation by using Andreasen apparatus and Coulter
counter apparatus. None of these methods are direct methods. However microscopic method
allows the observer to view the actual particles. The sedimentation method yields a particle
size relative to the rate at which particles settle through a suspending medium.

Rheological studies
Rheologic methods can help in determining the settling behaviour of the suspension.
Brookefield viscometer with variable shear stress control can be used for evaluating viscosity
of suspensions. It consist of T-bar spindle which is lowered into the suspension and the dial
reading is noted which is a measure of resistance the spindle meets at various levels in the
suspension. This technique also indicates in which level of the suspension the structure is
greater due to particles aggregates. Data obtained on aged and stored suspension reveals
whether changes have taken place.

Stability testing
It is not possible to conduct accelerated temperature studies as it can be done in solutions.
The formulation exhibiting thixotropic properties a rise in temperature would change the
properties. In this physical form, the preparation would exhibit parameters that could not be
extrapolated to those that would exist in the normal system. The valid temperature data could
be obtained that will be useful in the estimation of the physical stability of a product at normal
storage conditions. The extended aging tests must be employed under various conditions to
obtain the desired information.

SUSTAINED RELEASE SUSPENSIONS

A suspension usually gives a longer duration of action as compared to an aqueous solution
when given intramuscularly or subcutaneously. The drug is continuously dissolved to replenish
what is being lost. The constraints are imposed by stability, syringeability, pain upon injection
and minimum effective concentration. The sustained release by suspensions is achieved by
decreasing surface area, diffusion coefficient and solubility. An example of sustained release
suspension is that of insulin. Insulin is normally administered subcutaneously and it
precipitates as an insoluble complex in the presence of zinc chloride and depending on the pH
either an amorphous or crystalline form results. The crystalline form is less soluble than the
amorphous form and result in longer duration of action. Extended insulin zinc suspension USP
consist of crystalline zinc complex. Another example includes Penicillin G procaine a sparingly
soluble form of penicillin G. Others include medroxyprogestrone acetate (Depo-Provera),
triamcinolone hexacetonide (Aristopan) etc.

FORMULATION ADDITIVES
In addition to vehicle, stabilizer, sweetening and flavoring agents, which are common in liquid
dosage forms, the following additives are required to prepare suspensions which include:

Suspending and Thickening agents

They are added with the objective to increase apparent viscosity of the continuous, phase thus
preventing rapid sedimentation of the dispersed particles. The selection of the type and
concentration of a suspending agent depends on sedimentation rate of dispersed particles,
6 Md. Alamgir Kabir
Sr. Executive, Production
Beacon Pharmaceuticals Limited
pourability and spreadibility. The ideal suspending agent should have a high viscosity at
negligible shear i.e., during shelf storage and it should have a low viscosity at high shearing
rates i.e., it should be free flowing during agitation, pouring and spreadibility. A suspending
agent that is thixotropic as well as pseudoplastic should prove to be useful as it forms a gel on
standing and becomes fluid when shaken. They include natural polysaccharides (Gum Acacia,
Gum Tragacanth, Guar Gum, Sodium Alginate, Xanthan Gum and Carrageenan), Semi-
synthetic polysaccharides (Sodium Carboxymethylcellulose, Methyl Cellulose, Hydroxyethyl
Cellulose, Hydroxypropyl Cellulose, Hydroxypropyl Methyl Cellulose and Microcrystalline
Cellulose), Clays (Aluminium Magnesium Silicate, Bentonite and Hectorite) and synthetic
agents (Carbomer, Colloidal silicon dioxide). Pseudoplastic substances like tragacanth,
sodium alginate and sodium carboxymethyl cellulose show these desirable qualities. In cases
of combination use of suspending agents like bentonite and CMC dispersions are both
pseudoplastic and thixotropic.

A. Natural Polysaccharides
Gum Acacia: It is the dry exudates obtained from stems and branches of various species of
Acacia. It has low thickening properties but it is a good protective colloid. It is used in
combination with tragacanth and starch for internal preparations but is too sticky to be being a
natural product, acacia may be frequently contaminated with microorganism such as
Escherichia coli and Salmonella species and may need to be sterilized before use.
Preservative such as chloroform water, benzoic acid or hydroxybenzoates should be included
in formulations containing Gum Acacia.
Gum Tragacanth: Gum Tragacanth is dried exudates obtained from Astragalus gummifer or
other species of Astragalus. It is widely used as suspending agent in form of tragacanth
mucilage or compound tragacanth powder which consists of a mixture of acacia (20%),
tragacanth (15%), starch (20%) and sucrose (45%). Tragacanth forms viscous solution or gels
with water, depending on the concentration usually the powdered tragacanth is first dispersed
in a wetting agent, such as alcohol, to prevent agglomeration on the addition of water.
Tragacanth gels are non thixotropic and most stable at pH values between 4 and 7.5.
Tragacanth is non-toxic and almost tasteless and is widely used in suspensions for internal
use. Being less sticky, it may also be used for external applications.
Guar Gum: It consists of gum obtained from the ground endosperms of the seeds of
Cyamopsis tetragonolobus belonging to family Leguminosae. Guar Gum disperses in hot and
cold water to form a colloidal solution. A 1% aqueous dispersion has same viscosity to acacia
mucilage, while 3% dispersion has similar viscosity to tragacanth mucilage. Guar Gum is a
poor suspending agent for insoluble powders. It is employed as a thickener in lotions in
concentrations up to 2.5%. Maximum stability is achieved at pH values between 3 and 9.
Dispersions can be preserved with benzoic acid 0.2%.
Sodium Alginate: Sodium Alginate consists of purified carbohydrate product extracted from
brown seaweeds by use of dilute alkali. It chiefly consists of sodium salt of alginic acid.
Various grades are usually available commercially for different applications and yield solutions
of various viscosities. Sodium Alginate is slowly soluble in water. It is normally used in
concentrations of between 1% and 5%. A 1% solution has suspending properties similar to
those of tragacanth mucilage. Maximum stability is achieved at pH values between 4 and 10. It
is generally dispersed in a wetting agent, such as alcohol, glycerol or propylene glycol before
addition to water to prevent lump formation.
Xanthan Gum: Xanthan Gum consists of the purified polysaccharide gum obtained by
fermentation of a carbohydrate by bacteria of genus Xanthomonas chiefly Xanthomonas
campestris. It is soluble in hot and cold water and produces a viscous product that is stable
over a wide range of temperature and pH. A 1% solution has a viscosity of about 1000
centipoise. Xanthan Gum has been used as an alternative to tragacanth in the preparation of

7 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
suspensions. In comparison to tragacanth, it is easier to use and is capable of preparing
suspensions of better quality and improved consistency.
Carrageenan: Carrageenan consists of hydrocolloidal material extracted from certain red
seaweeds of class Rhodophyceae. It is soluble in 30 parts of water at 80o forming a viscous
clear or slightly opalescent solution. Dispersions of Carrageenan are stable at pH values
between 4 and 10. Carrageenan is used in pharmacy and the food industry as a suspending
and gelling agent.

B. Semi-Synthetic Polysaccharides
The Semi-Synthetic polysaccharides used as suspending and thickening agents mainly
consist of derivatives of the natural polysaccharide, cellulose.
Sodium Carboxymethyl cellulose: It is also known as Carmellose Sodium, it consists of the
sodium salt of Carboxymethyl ether derivative of cellulose. Different viscosity grades are
available which yield 1% aqueous solutions with viscosities in the range of 6 to 4000
centipoise. It is used in the concentrations ranging from 0.25% to 1% in suspensions meant for
oral, topical and parenteral use. It is soluble in hot as well as cold water forming stable
mucilage within the range of 5 and 10. Being anionic, it is incompatible with the cationic
compounds. Aqueous preparations that is unlikely to be stored for long periods should contain
an antimicrobial preservative.
Methyl cellulose: It consists of the ethyl ether derivative of cellulose. It dispersed slowly in cold
water to form colloidal solution but is insoluble in hot water. It is mainly employed as a
suspending and viscosity increasing agent for both internal and external preparations. Various
grades are available and are classified according to the viscosity of a 2% solution at 20o. The
use of the lower viscosity grades is preferred at concentrations up to 5% while higher viscosity
grades are used at concentration of 0.5% to 2%. An aqueous dispersion may be prepared by
adding the methyl cellulose to about one third the required amount of boiling water and when
the powder is thoroughly hydrated, adding the remainder of the water preferably in form of ice
and stirring until homogeneous. Methyl cellulose is nonionic and is stable over a wide range of
pH values. Heating an aqueous dispersion first causes a decrease in viscosity followed by
dehydration and gelling at 50o C. On cooling, however viscosity returns to normal.
Hydroxyethyl cellulose: It consists of the hydroxyethyl ether derivative of cellulose and is
mainly used as viscosity increasing agent. It is soluble in cold as well as hot water and
produces a clear solution that is stable even at higher temperatures. Various grades are
available that differs in their aqueous viscosities. Solution display maximum stability in pH
range 2 to 10.
Hydroxypropyl cellulose: It consists of hydroxypropyl ether derivative of cellulose and is mainly
used as a viscosity enhancing agent for oral and topical use. It is soluble in water below 40o C
and insoluble above this temperature. A wide range of grades are available that differs in their
aqueous solution viscosities. Maximum stability is demonstrated at pH range 2 to 10.
Hydroxypropyl methyl cellulose: It is also known as Hypermellose, it consists of the
hydroxypropyl derivative of methyl cellulose. It has properties similar to those of methyl
cellulose but produces aqueous solutions with higher gelling points. Various grades are
available that differs in their aqueous solution viscosities.
Microcrystalline cellulose: Microcrystalline cellulose is widely used as suspending agent,
either alone or in conjunction with other cellulose derivatives such as Carboxymethyl cellulose
sodium or hypermellose or with clays such as bentonite.

C. Clays

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Sr. Executive, Production
Beacon Pharmaceuticals Limited
Clays are inorganic materials, mainly hydrated silicates derived from natural sources. They
form highly thixotropic gels. The gels must be preserved with suitable antimicrobial agents as
clays are liable to heavy contamination with microbial spores.
Aluminium Magnesium Silicate: Also known as Veegum, Aluminium Magnesium Silicate is
mainly used at a concentration range of 0.5% to 2% as a suspending agent for both internal
and external preparations. A number of different grades are available; which are distinguished
by the degree of alkalinity and the viscosity of an aqueous dispersion. Dispersions in water are
thixotropic, and at concentration of 10% a firm gel is obtained. The viscosity of dispersions is
increased by heating, by addition of electrolytes and at higher concentration by ageing.
Bentonite: Bentonite is a natural colloidal hydrated aluminium silicate found in the midwest of
USA and Canada. Although it is insoluble in water, it absorbs large quantities of it and may
swells up to 12 times its original volume. Bentonite in contact with water forms either sols or
gels depending on its concentration. It is generally used at a concentration in between 0.5% to
2% for suspending powders in aqueous preparations such as calamine lotion. Dispersion
shows maximum stability at pH values between 3 and 10.
Hectorite: Hectorite is a natural colloidal magnesium silicate having properties similar to
bentonite. It swells up to 36 times its original volume and forms highly thixotropic gels at
concentration of 1 to 2%. It may contain traces of lithium and fluorine and is mainly used in
suspensions for external use.

D. Synthetic Agents:
The quality of synthetic agents tends to be less variable than that of suspending agents
derived from natural sources.
Carbomer: Carbomer is a high molecular weight polymer of acrylic acid crosslinked with allyl
sucrose. It dispersed in water to form an acidic colloidal solution of low viscosity, which
produces a high viscous gel on neutralization with inorganic or organic bases like sodium
hydroxide, triethanolamine, etc. several viscosity grades are available and the usual
concentration used varies from 0.1% to 4% as suspending agent. Carbomer gels are most
viscous between pH 6 and 11. The viscosity is reduced on lowering the pH to below 3 or rising
above 12. Electrolytes also reduce the viscosity of carbopol dispersions. Carbomer is
susceptible to oxidation especially on exposure to light and hence formulations should be
stabilized by addition of appropriate antioxidants and chelating agents. Aqueous dispersion of
Carbomer should also contain an antimicrobial preservative.
Colloidal Silicon dioxide: This is a form of Silicon dioxide having colloidal dimensions. It acts
as a suspending agent by forming aggregates which associates to form three dimensional
networks, thus preventing sedimentation. In a concentration between 1.5 to 4%, it acts as a
suspending stabilizer while at higher concentrations, it forms a soft gel. Aqueous dispersions
generally have a pH of 4 and neutralization does not affect the binding capacity.

Wetting agents
Although some insoluble solids get easily wetted by water, most of them exhibits
hydrophobicity and does not get easily wetted by it. Wetting agents are additives which are
usually added to decrease this hydrophobicity. These agents generally get adsorbed at the
solid-liquid interface and promote wetting of the solid particles by the liquid of the dispersion
medium. A variety of substances including the following have been employed as wetting
agents.
Surfactants: Generally, Surfactants possessing HLB values between 7 and 9 have been
employed as wetting agents. These orient themselves at solid-liquid interface and decrease
the interfacial tension between the particles of the dispersed phase and the dispersed
medium. Most surfactants are used at concentration of 0.1 to 0.2%. The minimum
concentration that is sufficient to cause wetting should generally be employed since an excess

9 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited
of these agents may cause foaming in the preparation. Examples of surfactants employed for
oral preparation includes polysorbates, sorbitan, esters, etc. for external preparations, sodium
lauryl sulfate, sodium dioctyl sulfosuccinate and quillia extracts can also be used.
Hydrophilic Polymers: Various hydrophilic colloids such as acacia, bentonite, colloidal silicon
dioxide and cellulose derivatives have also been employed as wetting agents. These act by
coating the surface of hydrophobic particles and imparting hydrophilic character to these.
Hydrophilic Liquids: Hydrophilic liquids such as alcohol, glycerol, propylene glycol, etc. are
sometimes employed as wetting agents. These penetrate the loose aggregates of solid
particles and displace the air from the pores thus facilitating wetting of the particles by the
dispersion medium.

Dispersing agents
These additives are generally added as an aid to uniform distribution and dispersion of solid
particles of the dispersed phase. Such agents are generally used during the preparation of
deflocculated suspensions where they get adsorbed at the solid-liquid interface. Wetting
agents such as surfactants are often employed as dispersing agents. Other agents used for
this purpose include agents such as Darvans, Daxads, etc. which carry a good surface charge
and get absorbed on the particles of the dispersed phase thus preventing their agglomeration.

Flocculating agents
These are substances added to cause controlled aggregation of the particles of the dispersed
phase in a suspension. Examples of such agents include surfactants, electrolytes and
hydrophilic polymers.
Surfactants: Ionic as well as non-ionic surfactants may be employed as flocculation agent. The
ionic surfactants such as sodium lauryl sulphate and sodium dioctyl sulfosuccinate act by
neutralizing the surface charge on the particles of the dispersed phase, thereby reducing inter-
particulate repulsion and causing aggregation. Non-ionic ones such as Spans and Tweens are
believed to function by formation of bridges between the adjacent particles.
Electrolytes: Electrolytes such as sodium salt of acetates, phosphates and citrates have been
commonly employed as flocculating agents. These acts by neutralizing the surface charge on
the particles of the dispersed phase thereby reducing the electrical barrier between them. The
effectiveness of the electrolytes as flocculating agents depends on the valance of the ions of
these electrolytes. Thus, divalent ions are ten times more effective then the monovalent ions
while trivalent ones are thousand times more effective. The concentration of the electrolytes
used should be minimum that is required to cause flocculation since an excess may cause
reversal of this phenomenon.
Hydrophilic Polymers: Hydrophilic polymers such as alginates, cellulose derivatives,
tragacanth, carbomers, silicates, etc. have also been know to cause flocculation of particles of
the dispersed phase. These polymers have a linear branched chain structure and form a gel
like network within the system. They get adsorbed on to the surface of the dispersed particles
and hold them in a flocculated state.

10 Md. Alamgir Kabir

Sr. Executive, Production
Beacon Pharmaceuticals Limited