Suspension

Definition

A pharmaceutical suspension is a two-phase system preparation containing finely

divided drug particles dispersed (suspended, distributed uniformly) in a vehicle

(dispersing medium) in which the drug exhibits a minimum degree of solubility

The internal phase (therapeutically active ingredient) consisting of:

o insoluble solid particles having a range of size (0.5 to 5 µm) which is

maintained uniformly throughout the suspending vehicle with aid of single or
combination of suspending agent.

The external phase (suspending medium) is generally aqueous in some instance,

may be an organic or oily liquid for non-oral use.
 Uses
Oral administration :

o sweetened

o flavored formulations.

External routes of administration:

o non-sweetened as lotions, intraocular, intranasal, etc.

Parenteral routes :

o IM, ID, SC.

 Characteristics

Uniform particle size:

o all particles behave alike and produce consistent behavior for the suspension
as a whole.

No particle-particle interaction:

o each particle remains discrete with no aggregation or clumping.

No sedimentation:

o drug particles are either stationary or move randomly throughout the

dispersion medium, so the drug is uniformly dispersed
Thixotropic and pseudo-plastic:

o it should have low viscosity at high shear rates (during shaking, pouring, or
spreading) and should have high viscosity at low shear rates (during storage).

Suspensions for internal use must be palatable and suspensions for external use
must be free from gritting particles.
 Suspension Advantages

Proper dosage form for drugs that are insoluble in all acceptable media.

Ideal dosage forms for patients who have difficulty swallowing tablets or
capsules.

Drugs in suspension are chemically more stable than in solution.

To achieve controlled/sustained drug release.

Suspension can mask the unpleasant/ bitter taste of drug.

 Suspension Disadvantage

Physical instability:

o suspensions tend to settle over time leading to a lack of uniformity of dose. This can be
minimized by careful formulation and by shaking the suspension before each dose is
delivered.

The texture of suspensions may be unpleasant to patients and should be carefully considered
during formulation.

It is bulky, care during handling and transport.

It is difficult to formulate.

Uniform and accurate dose cannot be easily achieved unless suspension are packed in unit dosage
forms
 Types of dispersed particles

Diffusible and dispersible powders:

o insoluble powders which are light in density and easily wettable,

o such as light kaolin, Mg trisilicate, and light Mg carbonate.

o They mix readily with water and on shaking they diffuse evenly through the liquid for
as long as dispensing needs.

In-diffusible powders are insoluble powders such as Calamine, Zinc oxide.

Reducing particle size or increasing the density slows down the rate of sedimentation of
the particles which lead to higher stability of the system.
 Control of Physical stability

Adding flocculating agents to enhance particle dispersability.

Flocculating agents are re ionic surfactants, or polymers, such as cellulose derivatives and
starch.

o They are electrolytes which carry an electrical charge opposite that of the suspended
particles.

o Adding the flocculating agent, affects the surface charge on the suspended particles
and allows the formation of floccules or clusters as particles are held loosely together
by weak forces.
Particles will not cake and may be easily redispersed by shaking the suspension.

o Floccules have approximately same size particles; a clear boundary is seen when the
particles settle.

o If we apply flocculation as a means of preventing caking, then we will increase the

particle diameter, and thus increase the rate of sedimentation.
Adding viscosity enhancers to reduce sedimentation rate in the flocculated suspension

o Viscosity enhancers are suspending or thickening agents are added to suspensions to thicken
the suspending medium, and so, reduce sedimentation of suspended particles and physically
stabilizing the product.

o Rapid particle settling is the primary factor leading to physical instability and lack of dosage
uniformity in the product.

o Typically, the concentrations used range from 0.5% to 5%, but the needed viscosity will
depend on the suspended particle’s tendency to settle.
Viscosity enhancers include agents from each of the following categories:

o Natural hydrocolloids: Acacia, tragacanth, alginic acid, carrageenan, guar gum, gelatin.

o Semisynthetic hydrocolloids: Methylcellulose, sodium carboxymethylcellulose.

o Synthetic hydrocolloids: Carbopol®

o Clays: Bentonite, Veegum®

The use of deflocculated particles in a structure vehicle may form solid hard cake upon
long storage.

o The system should be pseudo-plastic; it should have high viscosity at low shear rates
(during storage) and low viscosity at high shear rates (during shaking, pouring, or
spreading).

o Suspending agents which are thixotropic as well as pseudoplastic are desirable, since
they recover slowly from the deformation that occurs through shearing (i.e. upon
shaking, they remain fluid long enough to be poured and spread).
 Suspension forms

Ready to use form:

o In this type of suspensions the drug is already distributed throughout a liquid vehicle
with or without stabilizers and other pharmaceutical additives.

Dry powder for reconstitution:

o The dry powder is intended for suspension in liquid vehicle at the time of use, e.g.
antibiotics.
 Suspension Ingredients

API

o These should be finely divided insoluble solids and particle sizes ranging from 0.5 to
5.0 microns

Wetting agents (surfactants)

o They are surface-active agent with an HLB value between 7 and 9 and are used at a
low concentration (0.05 – 0.5%) for the formulation of suspensions to wet the
hydrophobic drugs with solvent.

o Examples of wetting agents include propylene glycol, sodium lauryl sulphate,

polysorbate, docusate sodium, sorbitan fatty acid esters, and glycerin.
Flocculating agents :

o These are excipients that function as wetting and suspending agents in a suspension
and facilitate suspended particles to link together in flocs or loose aggregates.

o These flocs rapidly settle but form large fluffy sediment which is redispersed easily.

o Examples include electrolytes, surfactants (sodium lauryl sulphate, tweens, and

span), sodium or potassium chloride, and polymers.
Thickeners (viscosity enhancers):

o They are added to increase the viscosity of suspension.

Buffers and pH adjusting agents:

o In a pharmaceutical suspension, a buffer is very important to maintain a

stable pH so that the API may be chemically stable within this suspension.

o Examples include citric acid, anhydrous citric acid (for powder for
suspension), carbonates, phosphate, gluconates, succinate, and acetate.

Coloring agents:

o They are added to impart desired color to suspension and improve elegance.
Flavoring Agents:

o producing pleasant flavors.

o Examples include anise oil, spearmint oil, orange essence, ethyl maltol, eucalyptus oil,
adipic acid and almond oil etc.

Coloring Agents :

o producing pleasant colors.

o Examples include caramel, ferric oxide, titanium dioxide, aluminum oxide, and FD & C
Red #40.

Sweetening Agents :

o overcoming the unpleasant taste of the pharmaceutical suspension.

o Examples are sucrose (up to 80%), sorbitol, mannitol, sodium saccharin, and aspartame
etc.
Anti-oxidants:

o These excipients prevent oxidation.

o Examples include ascorbic acid, α-tocopherol, erythorbic acid, glycerol,

carotenes, cytosine, acetylcysteine, etc.

Preservatives:

o They are added for the preservation or the protection of the suspension from
microbial contaminations.

o Examples include methylparaben (0.2%), propylparaben (0.05%),

butylparaben, propylene glycol (15-30%), benzalkonium chloride
(0.004-0.02%), sodium benzoate, benzoic acid (0.1-0.5%).
External liquid vehicle:

o They are added to construct structure of the final suspension. They are used as a
continuous medium in a suspension.

o Examples include water, alcohol, glycerin, polyethylene glycol, and polypropylene

glycol.
 Small scale preparation of suspensions

Step 1:

o Suspensions are prepared by grinding (or) levigating the insoluble materials in the
mortar to a smooth paste with a vehicle containing the wetting agent.

Step 2:

o All soluble ingredients are dissolved in same portion of the vehicle and added to the
smooth paste to step1 to get a semi-liquid mixture.

Step 3:

o The mixture is transformed to a graduated cylinder, the mortar is rinsed with

successive portion of the vehicle.
Step 4:

o Decide whether the solids are: suspended in a structured vehicle (OR) flocculated (OR)
flocculated and then suspended.

o Then, add the vehicle containing the suspending agent (or) flocculating agent

Step 5:

o Make up the dispersion to the final volume.