Pharmaceutics I Suspension & Dr.

Hana Amr FaYed

Suspension

Suspensions a Definition: -It is a dispersion of finely divided insoluble solid particle "the
dispersed phase "in fluid "the dispersion medium"

Properties of a well formulated suspension

Types of dispersion medium:
(characters)
1. Most pharmaceutical suspensions 1. Remain sufficiently homogenous for period
consist of an aqueous dispersion between shaking the container and removing the
medium required dose
2. It may be an organic or only 2. The sediment product easily resuspended by
liquid agitation
Example: 3. The suspension required to be thickened to reduce
1. Al Hydroxide suspensions the rate of settling of the particles
2. Mg hydroxide suspensions 4. The suspended particles should be small and
uniformly sized to give a smooth, elegant product

Pharmaceutical applications of suspensions

1. Used for the people which are difficulty in swallowing of solid dosage forms
2. Stable liquid dosage form made by suspending the insoluble ca+2 salt in a suitable
aqueous vehicle
3. Some materials are required to be present in the gastrointestinal tract in a finely
divided form and their formulation in suspension will provide high surface area
4. Solids such as kaolin, carbonate and Mg trisilicate are required to be present in
gastrointestinal tract in a finely divided form Why??
Their formulation as suspension will:
 Provide the desired high surface area
 Allow their ability to adsorb toxins or to neutralize excess acidity
5. Volatile components (thymol – menthol)  if prepared in solution  lost very rapidly

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So that give more prolonged release if it is absorbed on light MgCo3 before the preparation
of suspension
6. The lost of most drugs are not desirable if in solution than in an insoluble form such as
paracetamol a) volatile in solution, b) as elixir, c) as suspension this is more palatable
and suitable for children
7. Formulated for topical applications such as calamine lotions such as semisolid e.g.
pastes which contain high concentration of powder
8. Formulated for parenteral administration to control the absorption of the drug
9. Vaccines: for induction of immunity are formulated as suspensions as in cholera and
tetanus vaccines
10.Some X- ray contrast media such as Barium sulphate - for the examination of the
alimentary tract is available as a suspension for other oral or rectal administration.

N.B.

a) The prolong contact between the solid drug particles and the e.g. Ampicillin
dispersion media can be reduced by the preparation of the
suspension immediately before use by the patient
b) The drug which degrades in the presence of water may be suspended in a non-aqueous
vehicle
e.g. Phenoxymethylpenicillin is available for oral use as a suspension in coconut oil
c) Some drugs are hydrolyzed rapidly in aqueous solution
e.g. Oxytetracycline hydrochloride so it is used in solid dosage form
d) The degradation of a drug in the presence of water lead to decreasing its chance to
prepared as suspension so it may be possible to synthesize an insoluble derivatives
which can then formulated as in suspension

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Formulation of suspension

1- The drug to be suspended should be small particle size to

a) retard the rate of sedimentation of a suspended particle
b) to control the rate of release of the drug and its bioavailability
A) Particle size N.B.
control
Large particles
If greater than 5 microns in diameter it will cause irritation if injected
or installed into the eyes
Definition: These are materials used to reduce the interfacial tension

B) The use of between the solid and the liquid so that the adsorbed air is displaced
wetting agents from the solid surface by the liquid.
The particles then dispersed readily throughout the liquid
Role of wetting agents in suspension formulation: -
 According to the hydrophobicity degree some particles will form large porous
clumps within the liquid while the other remain on the surface and become
attached to the upper part of the container
So, the interfacial tension between the solid and the liquid must be reduced to ensure
adequate wetting.
So that the adsorbed air is displaced from the solid surface by the liquid the particles then
disperse readily throughout the liquid if an intense shearing action is used during mixing

The most widely used wetting agents in pharmacy

1) Surface active agents

 S.A.A possess HLB between 7-9 so can be as wetting agent
 The hydrocarbon chains would be adsorbed by the hydrophobic particle surface

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 The polar group would remain into the aqueous media become hydrated so wetting of
the solid would occur due to decrease the interfacial tension between the solid and the
liquid and between the liquid and air
 Most S.A.A are used in conc. Of up to 0.1% as wetting agent for:
a) Oral such as: polysorbates (Tweens), sorbitan esters (Spans)  non ionic
b) For external use such as sodium lauryl sulphate. (toxic if used oral)
Disadvantages of S.A.A as wetting agents
1. excessive foaming
2. possible formulation of deflocculated system which may not be required
2) Hydrophilic colloids:
- Such as acacia, bentonite, tragacanth, alginates and cellulose derivatives.
 Protective colloids by coating the solid hydrophobic particles.  increase the
hydrophilic character of the solid and increase the wetting
Disadvantages: may produce deflocculated system if used at low conc
3) Solvents
- Such as Alcohols, glycerol, glycols which are water miscible
 Reduce liquid/air interfacial tension so it will (solvent) penetrate the powder displacing
the air from the pores of the individual particles so cause wetting

Flocculation and Deflocculation

The suspension flocculated or deflocculated depends on the force of attraction between the
particles and on the electrostatic force of repulsion between the particles

Deflocculation Flocculation
Dispersed phase Separated particles (small) large particles size

Rate of sedimentation Slow Quick

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Difficult redispersed due to Easily redispersed (reversed)

Rate of redispersion the formation of caking or
clays

Dose Accurate before shaking Inaccurate

Sediment Clay or a cake Loose (Fluffy)
The supernatant Remain cloudy Become clear quickly
because the floss settles
rapidly
For fresh prepared For long prepared
N.B

Flocculated system with high viscosity to prevent

sedimentation taken would be an ideal situation

Disadvantages of Deflocculation:

The slow rate of settling prevents the entrapments of

liquid within the sediment which thus becomes
compacted and can be very difficult to redispersed

Degree of flocculation:

It is necessary to change the suspension from deflocculated into flocculated by the

addition of “Flocculating agent”:

1) Electrolytes:
 Alter the zeta potential of the dispersed particles and it is lowered, the flocculation may
occur
Ex: inorganic electrolytes such as sod. Salts of acetates, phosphates and citrates

N.B.
1- Trivalent electrolytes are less widely used than monovalent electrolytes because they
are more toxic
2- Not add excessive electrolytes as reversal may occur- deflocculated system occur again
2) Surfactant.
Ionic S.A.A may cause flocculation by neutralization of the charge on each particle
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3) Polymeric flocculating agents

 Such as starch, alginates, cellulose tragacanth, silicates derivatives.
Molecules form a gel like network within the system and become adsorbed onto the surface of
the dispersed particle thus holding them in a flocculated state

Rheology of suspension

An ideal pharmaceutical suspension would exhibit high apparent viscosity at low rate of shear.
(Pseudoplastic)

So, on storage: the suspended particle will settle very slowly or remain suspended

The apparent viscosity should

 Sufficient for the product to be poured easily from the container

 If the product used externally
a) The viscosity allows the product to spread easily without excess dragging
b) Should not be so fluid that run off the skin surface
 If intended for injection: the product should pass easily through a hypodermic needle
with moderate pressure Applied to the syringe pas plunger

Viscosity modifiers

A) Polysaccharides
 For aqueous media
 Natural material used as thickening agent (not good)
 it's value as a suspending agent due to its action as a protective
1- Gum acacia colloid
"gum Arabic"
 acacia mucilage become acidic on storage due to enzyme activity
 Contains oxides enzymes which cause deterioration of active agents
which are susceptive to oxidation

2- Tragacanth  For aqueous media

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 It is thixotropic and pseudoplastic in its properties

 It is better thickening agent than acacia
 Used for both internal and external products
 Stable at pH 4-7.5
 Its viscosity is affected by heating (disadvantages)
 Its mucilage must not be heated above 60 0C as depolymerization
occur with a loss of viscosity

3- Alginate  It exhibits a maximum viscosity over a pH range of 5-9 and at low pH

the acid is ppt
 Example sodium alginate
 Rarely used

4- Starch  It is derivative of potato starch

 Used with C.M.C
B) water soluble cellulose
 Semi synthetic polysaccharide and produce by methylation of
1- Methyl
cellulose
cellulose
 It is non-ionic so that it is stable over wide pH range from 3- 11
 Compatible with many ionic additives
2- Hydroxyl  Soluble in hot and cold water
ethyl cellulose  Not gel on heating
 Has the same properties as methyl cellulose
3- hydrated e.g. bentonite, Mg Al silicate
silicates  Belong to group called montmorillonite clays
 Absorbing up to 12 time their weight of water at elevated temperature
C) colloidal silica dioxide
Used in conc. Up to 4 % for external use
Used as thickening of non-aqueous suspension ‫مهمه‬

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Formulation additives

In order to maintain: chemical stability, control toxicity and to ensure

1- Buffer
physiological compatibility
Ex: glycerol and propylene glycol
2- Humectants  Used in a conc. of 5 % for external application
 Used as antidrying
 Prevent the growth of micro-organism which may be present in the
3- Preservation
raw material

Stability testing of suspension

The physical stability of a suspension is assessing by

1. Measurement of rate of sedimentation

2. The final volume
3. Height of the sediment
4. The ease of redispersion of the product

the first two parameters determined by measuring the total initial volume or high of
the suspension " Vo" and the volume of height of sediment "Vu" so. By plotting the
value of Vu/Vo against time for a series trial formulation

the slop of each line which suspension show the slowest rate of sedimentation is
determined
when the value of Vu/Vo become constant this indicate that sedimentation has ceased

The sedimentation volume, F, is the ratio of the equilibrium volume of the sediment, Vu to the
total volume of the suspension, Vo

𝑣u
𝐹= (Sedimentation volume)

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𝑣0
Pharmaceutics I Suspension & Dr. Hana Amr FaYed

𝐅 <1

𝑭>1

𝐅= 1
𝑣u
F( ) less than 1 is ordinary case, when the suspension settles to a certain volume of sediment
𝑣0
less than the volume of suspension.

 It is possible to have F values greater than 1, when the ultimate volume of the sediment
is greater than the original volume of the suspension. The particles in the suspension
create such a loose network of flocs that the floc comes out of the dispersion medium.
𝑣u
F( ) equal to 1 when the product shows no clear supernatant when the both volumes are
𝑣0
equal i.e., Vu =Vo. It is in state of flocculation equilibrium, it is an acceptable product

The redispersion of the product

 The ease of redispersion of the product determined qualitatively by the simple agitation
of the product in to container

Preparation of suspension

1) On small scale

a) Grinding the insoluble material in the mortar to a smooth paste with a vehicle containing
the dispersion stabilizer
b) Adding the remainder of the liquid phase in which any soluble drugs may be dissolved
c) Transfer to graduate and rinse the mortar with the vehicle
d) Complete to the final volume

2) On large scale

 By using ball or colloidal mill