PHARMACEUTICAL

SUSPENSIONS

mohd_kaleemullah
@msu.edu.my
 Pharmaceutical Suspensions
Definition:
 Suspensions may be defined as preparations containing finely divided drug
particles (the suspensoid) distributed somewhat uniformly throughout a
vehicle in which the drug exhibits a minimum degree of solubility.
Two forms of suspension

- Ready-to-use: drug already distributed through a

liquid vehicle with or without stabilizers and other
additives.

- Dry powder: a powder mixture containing the drug

and the suitable suspending and dispersing agent
to be diluted and agitated with specified quantity of
vehicle (Eg- those drugs are unstable for extended
time in presence of aqueous vehicle).
Commercial oral suspension
 Pharmaceutical Suspensions

• Commercial antibiotic preparation for oral suspension

following reconstitution with purified water.

• Left, dry powder mixture. Right, suspension after

reconstitution with the specified amount of purified water.
 Suspension
Suspensions are widely used for the following
administration.
SUSPENSIONS
 Reasons for Suspensions
There are several reasons for preparing suspensions.

1. When the drug is insoluble in the delivery vehicle.

2. Certain drugs are chemically unstable in solution but stable when

suspended.

 In this instance, the suspension ensures chemical stability while

permitting liquid therapy.

3. For many patients, the liquid form is preferred to the solid form of the
same drug because of the ease of swallowing liquids and the flexibility in
administration of a range of doses.

 This is particularly advantageous for infants, children, and the elderly.

 Reasons for Suspensions
3. The disadvantage of a disagreeable taste of
certain drugs in solution form is overcome when
the drug is administered as undissolved particles
of an oral suspension.

4. To achieve controlled/sustained drug release.

 Advantages
1. Pharmaceutical suspensions are a useful drug delivery system for
therapeutic agents that have a low solubility.

Although low-solubility therapeutic agents may be solubilised and

therefore administered as a solution, the volume of the solvent
required to perform this may be large. In addition, formulations in
which the drug has been solubilised using a co-solvent may exhibit
precipitation issues upon storage.

2. Pharmaceutical suspensions may be formulated to mask the taste of

therapeutic agents.

3. Pharmaceutical suspensions may be employed to administer drugs to

patients who have difficulty swallowing solid-dosage forms.

4. Pharmaceutical suspensions may be formulated to provide controlled

drug delivery, e.g. as intramuscular injections.
 Advantages
5. Allow an appropriate quantity of drug in a reasonably small
volume.

6. Resistance to oxidation and hydrolysis is good as compare

to aqueous solution

7. Masking of the taste of the drugs.

8. Children preferred suspension in comparison to

tablets/capsules

9. Drug in suspension exhibits higher rate of bioavailability

than other dosage forms.

Solution > Suspension > Capsule > Compressed Tablet >

Coated tablet
 Disadvantages
1. Pharmaceutical suspensions are fundamentally
unstable and therefore require formulation skill
to ensure that the physical stability of the
formulation is retained over the period of the
shelf-life.

2. The formulation of aesthetic suspension

formulations is difficult.

3. Suspension formulations may be bulky and

therefore difficult for a patient to carry.
 Disadvantages
4. No uniform and Accurate dose due to
redispersibility.

5. Sedimentation and compaction

6. Difficult to formulate.
Classifications
Based on Electrokinetic Nature of Solid Particles

 Flocculated suspension

 Deflocculated suspension

SUSPENSIONS
 Types of Suspension
Flocculation
 Flocculation is the formation of light, fluffy
groups of particles held together by weak Van
der Waal's forces.

 The basic concern in developing a suitable

suspension is to adequately control the rate of
settling and ease of redispersion, as well as, the
prevention of caking the particles as a dense
mass at the bottom of the container.

 These particles settle rapidly, forming a loose

adhering system with a large sediment height.
In contrast to deflocculated particles,
flocculated suspensions can always be
resuspended with gentle agitation.
Deflocculation
 Deflocculation is the absence of association which occurs
when repulsive forces between particles predominate.
Particles repel each other and remain as discrete, single
particles.

 If repulsion forces prevail, the particles separate or

deflocculate.

 Particles in these systems settle very slowly in stages, but

ultimately form a dense sediment which is considerably
more compact than the corresponding sediment of a
flocculated system and more difficult to resuspend.

 In order to stabilize deflocculated systems, it is necessary to

add a suspending and/or a gelling agent to retard settling
and agglomeration of the particles by functioning as an
energy barrier.

 Good pharmaceutical suspensions are best achieved

through the formation of a stable floc which resists the
tendency toward either deflocculation or agglomeration.
 Properties of Flocculated suspension

• Particles form loose aggregates

• Rate of sedimentation is high and particles settle
as floc
• A sediment is formed rapidly
• The sediment is loosely packed. So does not form
a hard, dense cake
• Sediment is easy to re-disperse
• A clear supernatant region is observed due to
rapid sedimentation which is somewhat unsightly
 Properties of deflocculated suspension

• Particles exist in suspension as separate entities

• Rate of sedimentation is slow, since each particle settles
separately and particle size is minimal
• A sediment is formed slowly
• A hard cake is formed because-
- Sediment eventually becomes very closely packed due to
weight of upper layers and
- Repulsive forces between particles are overcome
• Difficult, if not impossible, to re-disperse
• Has a pleasing cloudy appearance, even when settling is
apparent
 THEORITIC CONSIDERATION
OF SUSPENSIONS

Some theoretic considerations are :

Physical features of the dispersed phase of a suspension

 Dispersion medium

Sedimentation

Aggregation

Particle size control.

Wetting
 THEORY OF SEDIMENTATION

SEDIMENTATION:

Sedimentation means settling of particle (or) floccules occur

under gravitational force in liquid dosage form.

 SEDIMENTATION

2 SUSPENSIONS
3
Formulation of
Suspensions
 Wetting Agents

 The most commonly used Wetting agents 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.

 The concentration used is less than 0.5 %.

 Wetting Agents

Solid
particles Hydrophilic can be
dispersed easily

Suspending
media

Difficult to disperse and

float on the surface due to
hydrophobic surface or
entrapped air

38
 Suspending agents

Reasons :it forms collidal dispersions with water

and increases the viscosity of continuous phase.
so that the solid drug particles remain
suspended in the continuous phase for sufficient
long time to measure a uniform accurate dose

39
 Suspending agents

 Suspending agent are also known as hydrophilic colloids

which form colloidal dispersion with Water and increase the
viscosity of the continous 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.

40
 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.
.

41
Stability pH range and concentrations of most commonly used suspending agents.
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 3-11 1-2%
methylcellulose
CMC 7-9 1-2%

Colloidal 0-7.5 2- 4 %
silicon dioxide

42
 Surfactants

 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 following advantages

 It is non-ionic so no change in pH of medium

 No toxicity. Safe for internal use.
SUSPENSIONS 43
 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.

44
. Generally pH 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.

45
 Preservatives

 Naturally occurring suspending agents such as tragacanth, acacia,

xanthan gum are susceptible to microbial contamination.

This leads to:

 loss in suspending activity of suspending agents,

 loss of color, flavor and odor,
 change in elegance etc.

Reasons: to preserve the suspension against bacterial growth

46
Name of preservatives Concentration range

Propylene glycol 5-10%

Disodium EDTA 0.1%
Benzalkonium chloride 0.01-0.02%
Benzoic acid 0.1%
Butyl paraben 0.006-0.05% oral
suspension
0.02-0.4% topical
formulation

Disodium EDTA benzalkanonium

47
 Sweetening Agents
They are used for taste masking of bitter drug particles.

Bulk sweeteners

 Sugars such as xylose, ribose, glucose, mannose.

 Sugar alcohols such as sorbitol, xylitol, mannitol

A bulk sweeteners is used at concentration of 15-70 %

SUSPENSIONS 48
Artificial sweetening agents

•Sodium cyclamate

•Sodium saccharin

•Aspartame

SUSPENSIONS 49
 Flavoring And Coloring Agents

 They are added to increase patient acceptance.

 Only sweetening agent are not capable of complete taste masking

of unpleasant drugs therefore, a flavoring agents are incorporated.

50
Eg:
Acacia Ginger Sarsaparilla
syrup
Anise oil Glucose Spearmint oil
Benzaldehyde Glycerin Thyme oil

51
 Coloring agents

 Colors are obtained from natural or synthetic sources.

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 identification of the product.

 The color used should be acceptable by the

particular country.

52
Most widely used colors are as follows.

· Titanium dioxide (white)

· Brilliant blue (blue)

· Indigo carmine(blue)

· Amaranth (red)

Annatto seeds
·Tartarazine (yellow)
Annatto seeds(yellow to orange)

53
 Preparation of Suspensions
 In large scale preparation of suspensions, wetting agents are mixed with the
particles by an apparatus such as a colloid mill;

 on a small scale in the pharmacy, they are mixed with a mortar and pestle.

 Once the powder is wetted, the dispersion medium (to which have been added
all of the formulation’s soluble components, such as colorants, flavorants, and
preservatives) is added in portions to the powder, and the mixture is thoroughly
blended before subsequent additions of vehicle.

 A portion of the vehicle is used to wash the mixing equipment free of

suspensoid, and this portion is used to bring the suspension to final volume and
ensure that the suspension contains the desired concentration of solid matter.

 The final product is then passed through a colloid mill or other blender or
mixing device to ensure uniformity.
 Particles

Addition of wetting agent and dispersion medium

Uniform dispersion of deflocculated particles

A B C

Incorporation of Addition of Addition of

structured vehicle flocculating agent flocculating agent

Flocculated suspension
Flocculated suspension
as final product
Incorporation of
structured vehicle
Deflocculated suspension
in structured vehicle
Flocculated suspension
as final product
in structured vehicle as
final product
An industrial mixer for manufacture of disperse
systems, including suspensions and emulsions.
Liquid filling. Bottles being conveyed after cleaning. As they
pass through an indexing worm, the bottles are
spaced accurately for filling and capping.
Small scale preparation of suspensions:

Step 1:

Suspensions are prepared by grinding (or) levigating the insoluble

materials in the mortar to a smooth paste with a vehicle containing the

wetting agent.

58
Step 2:
 All soluble ingredients are dissolved in same portion of the
vehicle and added to the smooth paste to step1 to get slurry.

Step 3:

The slurry is transformed to a graduated cylinder, the mortar is

rinsed with successive portion of the vehicle.

59
 Step 4:
Decide whether the solids are
Suspended in a structured vehicle
Flocculated
Flocculated and then suspended

Add the vehicle containing the suspending agent (or) flocculating agent
Step-5

Make up the dispersion to the final volume .

Thus suspension is prepared.

60
 Packaging and Storage of Suspensions
 All suspensions should be packaged in wide mouth containers having
adequate airspace above the liquid to permit thorough mixing by shaking
and ease of pouring.

 Most suspensions should be stored in tight containers protected from

freezing, excessive heat, and light.

 It is important that suspensions be shaken before each use to ensure a

uniform distribution of solid in the vehicle and thereby uniform and proper
dosage.
 STORAGE :

 Suspensions should be stored in cool place but should not be kept

in a refrigerator

 Freezing at very low temperatures should be avoided which may

lead to aggregation Of suspended particles

0
Stored at controlled temperature from 20-25 c

62
 STORAGE REQUIREMENTS & LABELLING

Labelling:

Shake well before use

Do not freeze

Protect from direct light(for light sensitive drugs)

 In case of dry suspensions powder the specified amount of

vehicle to be mixed may indicated clearly on label.

63
Label:

64