Definition:

• Suspensions are heterogeneous biphasic liquid dosage form in which insoluble solid particles are uniformly
distributed in a liquid or semisolid vehicle.

• The solid particles act as disperse phase/ internal phase or discontinuous phase and liquid vehicle acts as
dispersion medium/external phase or continuous phase.

• These may require addition of suspending agent or stabilizer.

• The finely divided solid particles ranging from 0.5 to 5.0 micron.
• Advantages:

1. Bio-availability of finely dispersed or wet drug is faster than that of solid dosage forms. Bio-availability is in
following order. Solution> Suspension> Capsule>compressed tablet >coated tablet

2. Large doses of insoluble drug are easier to swallow in the form of suspensions than solid dosage forms e.g.
antacid and antidiarrheal preparations.

3. The higher surface area of suspended phase is more effective to exert their effect, e.g. insoluble antacids,
adsorbents such as kaolin pectin etc.

4. Drugs are chemically more stable in the insoluble state than in the soluble state.

5. Liquid preparations are easy to swallow so more useful for pediatric and geriatric patient.

6. Some drugs are not stable in solution form. In such cases it is necessary to6. prepare an insoluble form of that
drug. Therefore, drugs are administered in the form of suspension. e.g. Procaine Penicillin G.
7. Suspension can mask the unpleasant taste of drug e.g. paracetamol, chloramphenicol palmitate.

8. It is the choice of dosage form to present an insoluble drug in the liquid form.

9. Suspension is one of the techniques to attain slow and sustained drug release.

10. Suspension of drug can be formulated for topical application e.g. Calamine lotion, can be used for Parenterals
administration in order to control rate of drug absorption.

11. X-ray contrast agent are also formulated as suspension e. g. Barium sulphate for examination of alimentary
tract.
• Disadvantages:
1. A number of drugs have some solubility in commonly used solvents and this can lead to physical instability of suspension.

2. All suspensions are required to be shaken before use.

3. Accuracy of dose depends on uniform re-dispersion of sediment.

4. Drug particles could adsorb added flavors and colors and make a system difficult to formulate.

• Classification of suspension:
• Classification of suspension according to its pharmaceutical use:

1. Oral suspension (Mixture)

2. Parenteral Suspension

3. Suspension for external use

4. Ophthalmic, Nasal, Otic Suspension

Oral suspensions generally contain flavouring agent and sweetening agent to mask the bitter taste of drug. They are made
palatable by using suitable derivatives of drug e. g. Chloramphenicol palmitate suspension.

Suspension are also available in market as dry powder form and these are reconstitute by adding a specified quantity of
freshly boiled cooled water before use e.g. antibiotics in suspension for paediatric use. Examples are paracetamol
suspension, antacids.

2. Parenteral suspension:
Suspension which are administered by Parenteral route are called Parenteral suspension. Examples are Procaine penicillin-
G, Insulin Zinc Suspension. These suspensions are having following criteria;

i) The particle size of drug should be such that it can easily pass through the needle of the syringe.

ii) The concentration of solid particle s in the suspension should be between 0.5 to 30%.

iii) The viscosity of the suspension should not interfere with its flow through the syringe needle.
3. Suspension for external use:

These suspensions are meant for external use, e.g. Lotions like calamine lotion, sunscreen lotion. These
suspensions contain very small particles to avoid grittiness. Lotion must be applied to unbroken skin without
friction. Label of lotion should contain shake well before use and For external use only.

4. Ophthalmic, Nasal and Otic suspension:

The particle size of eye suspension should be fine enough so that it should be non-irritating to the eye. These
suspensions must be sterile, isotonic, have desired viscosity. Nasal suspension are aqueous in nature, isotonic with
body fluids and ph is adjusted between 5.5 to 6.5 Otic suspensions are mostly oily or non aqueous.

• Based upon proportion of solid particles:

i) Dilute suspension (2 to10%w/v solid) Eg: cortisone acetate, prednisolone acetate

ii) ii) Concentrated suspension (50%w/v solid) Eg: zinc oxide suspension
• Based on Electro kinetic Nature of Solid Particles:

1) Deflocculated suspension 2) Flocculated suspension

• Colloidal suspensions (< 1 micron): Suspensions having particle sizes of suspended solid less than about 1 micron
in size are called as colloidal suspensions.

• Coarse suspensions (>1 micron): Suspensions having particle sizes of greater than about 1micron in diameter are
called as coarse suspensions.

• Nanosuspensions: Suspensions are the biphasic colloidal dispersions of nano sized drug particles stabilized by
surfactants. Size of the drug particles is less than 1 mm.

• Formulation of suspension:

The formulation of a suspension depends on whether the suspension is flocculated or deflocculated.

Three approaches are commonly involved

1. Use of structured vehicle

2. Use of controlled flocculation

Controlled flocculation:
Controlled flocculation of particles is obtained by adding flocculating agents, which are:

(1) Electrolytes (2) Surfactants (3) Polymers. Sometimes suspending agents can be added to flocculated
suspension to retard sedimentation.

Examples of these agents are: Carboxyl methylcellulose (CMC), Carbopol 934, Veegum and bentonite.
• Components/Ingredients for formulation of suspension:

1. Wetting agents- They are added to disperse solids in continuous liquid phase.

2. Flocculating agents: They are added to floc the drug particles

3. Thickeners: They are added to increase the viscosity of suspension.

4. Buffers and pH adjusting agents- They are added to stabilize the suspension to a desired pH range.

5. Osmotic agents- They are added to adjust osmotic pressure comparable to biological fluid.

6. Coloring agents- They are added to impart desired color to suspension and improve elegance.

7. Preservatives- They are added to prevent microbial growth.

8. External liquid vehicle- They are added to construct structure of the final suspension.
1. Suspending agents or thickeners:

They are added to increase the viscosity of suspension. 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 inter particle attraction. Most suspending agents perform two functions, acting as a suspending agent as well as
imparts viscosity to the solution.

Suspending agents are classified into three major groups:

1. Polysaccharides:

i) Natural polysaccharides: Gum acacia, tragacanth, starch, sodium alginate.

ii) Semisynthetic polysaccharides: The following cellulose derivatives are used as thickening agents, Methyl cellulose- It is
used in the concentration of 0.5 to 2 % both in internal and external preparations.

Sodium carboxy methyl cellulose-It is used in concentration from 0.25 to 1% for suspending powders in preparations meant for
oral, external and parenteral use.

Microcrystalline cellulose-It is dispersible in water to produce colloidal dispersions

i) Clay: Bentonite is a very pale buff hygroscopic powder and aluminum magnesium silicate is a very creamy
white colorless and tasteless powder. It is used as thickening agent in both external and internal preparations.

ii) Aluminium hydroxide: It is used as suspending agent in suspension containing barium sulphate, calamine,
sulphonamide and Sulphur.

3. Synthetic compounds:

i) Carbomer: Carbomer are high molecular weight carboxy vinyl polymers. It is used in concentration of 0.1 to
0.4%.

ii) Colloidal silicon dioxide: It is used in concentration 1.5 to 4%.Preferred suspending agents are those that give
thixotropy to the media such as Xanthan gum, Carageenan, Na CMC/MC mixers, Avicel RC 591 Avicel RC 581
and Avicel CL 611.
2. Wetting agents:
They are added to disperse solids in continuous liquid phase. Some insoluble solid particles do not wet readily with
water and their lumps float on the surface of liquid. These are the substances which reduce the interfacial tension
between the solid particles and liquid medium. This may be achieved by the addition of suitable wetting agent
which is adsorbed at the solid/liquid interface in such a way that affinity of the particles for the surrounding
medium is increased and interparticular forces are decreased For example alcohol in tragacanth mucilage, glycerin
in sodium alginate, polysorbate in oral and Parenteral suspensions.

3. Surfactant :
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. Polysorbate- 80 is most widely used due to
its non-ionic property there is no change in pH of medium. No toxicity and safe for internal use.
4. Hydrophilic colloids: Hydrophilic colloids coat hydrophobic drug particles in one or more than one layer.
This will provide hydrophilicity to drug particles and facilitate wetting They cause deflocculating of suspension
because force of attraction is declined. e.g. acacia, tragacanth, alginates, guar gum

5. Solvents: The most commonly used solvents used are alcohol, glycerin, polyethylene glycol and
polypropylene glycol, The mechanism by which they provide wetting is that they are miscible with water and
reduce liquid air interfacial tension. Liquid penetrates in individual particle and facilitates wetting.

6. Buffers : Buffers are the materials which when dissolved in a solvent will 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, pHs of suspension
preferably at 7.4-8.4. Most commonly used buffers are salts of weak acids such as carbonates, citrates, gluconates,
phosphate and tartrates.
7. Osmotic agents: They are added to produce osmotic pressure comparable to biological fluids when
suspension is to be intended for ophthalmic or injectable preparation. most commonly used osmotic agents
are dextrose, mannitol, sorbitol, sodium chloride, sodium sulphate, glycerol.

8. Preservatives: The naturally occurring suspending agents such as tragacanth, acacia, xanthan gum are
susceptible to microbial contamination) A suitable preservative is needed to preserve suspensions against
bacterial growth. Benzoic acid, sodium benzoate, butyl paraben, methyl paraben, propyl paraben are
"commonly used as preservative.

9. Organoleptic additives: colouring agents, sweetening agents and flavouring agents are generally
incorporated in oral suspensions. Colouring and flavouring agents used are Ginger, Sarsaparilla syrup Anise
oil, Spearmint oil, Thyme oil.

Most widely used colours are Titanium dioxide (white), Brilliant blue (blue), Indigo carmine (blue),
Amaranth (red), Tartrazine (yellow); Annatto seeds (yellow to orange).Sweetening agents like mannitol,
10. Humectants:
Humectants absorb moisture and prevent degradation of API by moisture) Examples of humectants most
commonly used in suspensions are propylene glycol glycerol. Total quantity of humectants should be between 0-10
%w/w.

11. Antioxidant:
Ascorbic acid derivatives such as ascorbic acid, erythorbic acid, Thiol derivatives such as glycerol, cytosine,
acetylcysteine, Tocopherols, Butylated hydroxy anisole(BHA), Butylated hydroxyl toluene (BHT) Sodium
bisulfite, Sodium sulphate acetone.
Methods of compounding/Preparation of suspension:
Small scale preparation method:

A suspension is prepared on the small scale by grinding or levigating the insoluble material in the mortar to a
smooth paste with a vehicle containing the solubilizer and gradually adding the remainder of which any soluble
drugs may be dissolved. The slurry is transferred to a graduate, the mortar is rinsed with successive portions of the
dispersion medium is finally brought to the final volume.

1. Suspension containing diffusible solids:

There are certain insoluble powdered substances which are light in weight readily mix with water and remain
suspended throughout the liquid for sufficient long time after shaking. Such substances are known as diffusible
solids. For example, calcium carbonate, light magnesium carbonate, magnesium trisilicate, rhubarb powder and
light kaolin.
General method of compounding and dispensing:

1. Finely powder the solid ingredients.

2. Fine powder of drug is mixed with other solid additives by the doubling up method.

3. Powder blend is levitating with small amount of vehicles or suitable levitating agent in a mortar to produce a
smooth cream.

4. Soluble additives are first dissolved in the vehicle and added to smooth cream in small amounts, triturating
after each addition.

5. The resultant suspension made free from foreign particles by straining and it is poured in tarred bottle.

6. The final volume is adjusted with a remaining vehicle.

Substances which do not dissolve in water and do not remain uniformly distributed throughout the liquid for
sufficient long time to ensure uniformity of dose such substances are known as indiffusible solids Examples are
Calamine, Zinc oxide, sulphur precipitated are used externally and Aspirin, aromatic chalk powder, chalk,
sulphadimidine are used internally.

General method:

calamine lotion. The procedure to prepare suspension containing indiffusible solids is same as that of diffusible
solids only difference is that indiffusible solids requires a suspending agent which is mix with finely powdered
drug and triturated with small amount of vehicle to form smooth cream.
3. Suspensions containing Precipitated forming drug: Certain liquid preparations that is precipitated on
addition to water. For example, compound benzoin tincture, benzoic tincture, myrrh tincture and tolu tincture.
These liquids are insoluble in water and form indiffusible precipitates when salts are present. They contain
resinous matter and when it is mixed with water, it leads to precipitation of resin. To prevent this protective
colloid is dispersed in the vehicle before tincture is added. tragacanth mucilage (1/4 of the total volume) or
compound tragacanth powder (2g/100ml) is commonly used as protective colloid