2. A suspensions may be defined as a biphasic system comprising
of a solid phase ( the dispersed phase) uniformly dispersed in a
liquid phase (the continuous phase or dispersion medium).
The range of solid particles in suspension usually form 0.5 to 5
micron. Suspensions may either be colloidal which are similar in
appearance to solutions or coarse, which contain visible solid
particles.
Suspension is an ideal dosage form for the patients who can't
swallow solid dosage forms like tablet or capsule. Suspension
may be used in orally, parenterally or topically.
3. Properties of suspension
1. It should be easily swallow & administrated.
2. The dispersed particles should be small & equally sized in order to
give a smooth elegant product &free from gritty texture.
3. The dispersed particles should not settle instantly & the settle
particles should redisperse immediately on shaking.
4. The particles should not form a sediment on settling.
5. The viscosity should be optimum so as to the preparation can be
easily poured into administration route.
6. Suspension for internal use must be palatable & suspensions for
external use must be free from gritty particles.
7. It should be free from unpleasant odour,taste .
8. It must be resistance to microbial growth
9. It should be physically & chemically stable.
4. Classification of Suspension
☆ According to the aggregation of particles :
1. Flocculated suspension may be defined as a suspension in which
the dispersed insoluble solid particles exist in the vehicle or
continuous phase as a large clump or floccules.
2. Deflocculated suspension may be defined as a suspension in which
the dispersed insoluble solid particles exist as separate or
individual entities in the continuous phase.
7. Advantages of suspension
Suspensions posses certain advantages over other dosage forms. Like-
1. Drugs that degrades in solution can be used here.
2. Suspension is relatively easy to manufacture compared to other
dosage forms.
3. Suspensions permit the formulation of poorly soluble drugs as liquid
dosage form.
4. Suspension is an ideal dosage form for those patients who have
difficulty in swallowing tablets and capsules.
5. Suspension is easily absorbed than other dosage form except
solution. That's why we can get rapid therapeutic action.
6. This dosage form sometimes enhance stability of some drugs like
erythromycin,salicylate.
7. Certain drugs such as antibiotics that are unstable in aqueous solution
can be formulated as suspension to provide a stable product.
8. Drug in suspension have high rate of bioavailability than others :
Solution>Suspension>capsule>compressed tablet>coated tablet
8. Stroke's law in formulation of suspension
The law states that :
The rate of sedimentation of a particle in a liquid medium is -
Directly proportional to the diameter of the particle.
Directly proportional to the density difference between particle &
medium.
Inversely proportional to the viscosity of the medium.
9. Mathematical expression,
V = D2(d1 - d2)g / 18ἡ
= 2r2 (d1-d2) / 9ἡ
here,
V= velocity of sedimentation in cm/sec
r= particle radius in cm
D= particle diameter in cm
d1=density of the particle in gm/cc
d2=density of the medium in gm/cc
g= gravitational constant =980cm/sec2
ņ= viscosity of the medium.
10. Although stokes law play an important role for the preparation of a
stable suspension, it has got some limitations.
1. The equation can only be applied to dilute suspension where free
settling occur & can't be applied to concentrated solution.
2. Particles of the suspension should be rigid, spherical & uniform.
3. Suspension should not produce any type of turbulence when the
particles settle.
4. Pharmaceutical suspension usually do not follow stoke's law
because-
a. Suspensions are not usually dilute
b. Size of the suspended particles is not uniform.
c. Particles are not spherical
11. Sedimentation rate
The rate at which particles in a suspension is sediment is called
sedimentation rate. The rate of sedimentation is influenced by the
following factors :
1. Size and shape of the particle
2. Density of the particle
3. Density of the medium
4. Viscosity of the medium
5. Particle-particle interaction
6. Particle -fluid interaction
7. Brownian movement of the particle
12. Flocculating agents
Flocculating agents defined as the substances that can be added to
the medium of a suspension to promote flocculation by causing
colloids & other suspended particles to aggregate,forming a floc.
Example : Na lauryl sulphate, tragacanth, alginates, electrolyte,
polymers etc.
They act by-
1. Reducing the surface tension
2. Counteracting the effect of the protective layer
3. Reduce the electrical barrier between particles
4. Improving the dispersion of solids
5. Minimize flocculation.
13. ☆ Electrolytes-
Na salts of acetate, phosphate, citrate etc.
Mechanism:
The mechanism of action of electrolytes as flocculating agent is
not clear but it is assumed that the ions of electrolytes probably
reduce or neutralize the electrical barrier between the particles
and also form a bridge between the particle so as to link them
together as flocks
If the particles in the suspension are positively charged then
negative electrolytes are used e.g. monobasic K phosphate in
bismuth subnitrate suspension & vice versa e.g. AlCl3, in
sulfamerazine suspension.
14. ☆ Polymers:
Polymers are long chain molecules having side branches.
e.g. Starch, Cellulose derivatives alginates, tragacanth
Mechanism :
The commonly used polymers are the various hydrocolloids which not only
assist in flocculation but are helpful in increasing the viscosity of
continuous phase as well. Flocculation occurs when the polymers solubility
is decreased in dispersed medium.
The polymer contain active groups along their chains when they are added
to a suspension, they are absorbed by the following way-
1. Part of the long chain molecules may be absorbed onto the particles
leaving extended segments protruding from particle surface.
2. The protruding segments form a bridges between particles producing
flocculated product.
15. ☆ Surfactants
Surfactants used as flocculating are mainly ionic surfactants (anionic
or cationic). However nonionic detergents may also be used as
flocculating agents but they have little effect on densely charged
particles.
Mechanism:
An ionic surface active agent can be used to increase the
sedimentation volume. Nonionic surfactants may be adsorbed on to
the suspended particles and can produce flocculated systems at the
appropriate concentration i.e. they act adsorption mechanism.
16. ☆ Addition of liquid:
The addition of small amount of a liquid which is immiscible with
the continuous phase but wets the solid particles can produce
flocculation.
Hydrophobic solids in water can be flocculated by the addition of
a hydrophobic liquids
☆ pH of the medium:
The flocculating action is dependent on the pH & the ionic
strength of the medium & an optimum pH is observed for
sedimentation.
17. ☆ Bridging flocculation
An altenative way to control flocculation is by addition of a
hydrophilic polymer (e.g. starch, alginate and carbomer) that on
adsorption by drug particles will produce a surface film capable
of bridging between suspended particles to form floccules.
The polymer must contain chemical groups that can interact with
the surface of the particles. Polyacrylamide is an anionic polymer
that can flocculate by this mechanism.
18. How to understand the flocculation occurs or not?
The parameters which are used as semi quantitative measurements
of flocculation in a suspension are referred to as sedimentation
parameters.
There are 2 sedimentation parameters by which one can easily
understand whether flocculation occurs or not :
▪ Sedimentation volume(F)
▪ Degree of flocculation (B)
19. Sedimentation volume
The sedimentation volume is defined as the ratio the final volume
of the sediment to the original volume of the suspension.
Mathematical expression:
Let,
• The final volume of sedimention = Vu
• The original volume of total suspension= Vo
So, the Sedimentation volume (F) = Vu/Vo
20. Significance :
The sedimentation volume of a product may have a value of less
than, more than or equal to 1 .
1. If F<1, then Vu<Vo; it indicates the ordinary suspension ; where
the dispersed particle settle as sediment which have an final volume
less than the original volume of the suspension.
2. If F> 1, then Vu>Vo; it indicates that the final volume of sediment
is higher than original volume of suspension.
3. If F=1, then Vu=Vo; it indicates that final volume of sediment is
equal to original volume of suspension.
Such a product is quite acceptable from a pharmaceutical point of
view because on standing it shows no sediment & the product is
said to be in a state of flocculation equilibrium.
21. Degree of sedimentation
Degree of sedimentation may be defined as the ratio of
sedimentation volume of the flocculated suspension to the
sedimentation volume of the deflocculated suspension.
Mathematical expression :
Let, the original volume of suspension =Vo
The final volume of sedimention when flocculated = Vu
The final valume of sedimention when deflocculated =Vα
22. • Sedimentation volume of defiocculated suspension Fα = V α /Vo
• Sedimentation volume of floCculated suspension F = Vu/Vo
So, Degree of flocculation (B) = Vu/Vo / Vα /Vo
= Vu/V α
= Ultimate sediment volume of flocculated suspension /
Ultimate sediment volume of deflocculated suspension
Significance:
When the value of B is high, it indicates better flocculation.
The lower limiting value of B ie. 1 indicates no
flocculation.
23. Prevention of flocculation
1. Adsorption of ions from surrounding medium
2. Presence of suitable vehicle
3. Formation of electrical barrier
4. Formation of mechanical barrier
5. Minimum movement of particles
6. Changes the physical properties of ingredients
24. ☆ Manufacturing of Suspension
A. Small scale preparation
B. Large scale preparation
25. Small scale preparation
☆ For hydrophilic drugs:
1. First powdered drug takes in a mortar & triturate with pestle.
2. Suspending & flocculating agent take in another mortar & add water
slowly & triturate. A mixture of mucilage will be formed.
3. Afterthen, Triturated drug is mixed with small amount of mucilage &
triturate up to a paste is formed.
4. Now the rest of mucilage is slowly added & triturate.
5. After addition of all mucilage, colouring agent, flavouring agent,
preservative & antioxidant are added to the paste with stirring.
6. Finally appropriate volume of water is added to make the desired
volume of suspension.
26. ☆ For hydrophobic drugs :
1. First powdered drug takes in a mortar & triturate with pestle.
2. Triturated powdered drug is mixed with wetting agent to form a
triturated mixture.
3. Suspending agent is dispersed in water in another media.
4. Triturated mixture is now triturated with small portion of
suspending medium to form paste.
5. The rest of suspending medium is added slowly to the paste &
stirring.
6. Then add colouring, preservatives, antioxidants & flavouring
agents.
7. Finally appropriate volume of water is added to make the desired
volume of suspension.
27. Large scale preparation
1. A concentrated dispersion of the suspending agent is produced
first in a mixing vessel or tank. This is accomplished by adding the
material slowly to the vehicle & a homogenizer is used for mixing.
2. In another vessel, the active ingredient & wetting agents are
mixed with a portion of the vehicle by first stirring & then passing
through them through high pressure mixing machine. Eg.
Colloidal mill, ball mill.
3. The drug mixture is then shifted to the suspending agent-vehicle
dispersion by means of a pump & mixed properly
28. 4. Other ingredients are then added to this suspension, & the
whole made up to volume if necessary.
5. Finally the product is properly mixed by means of a suitable
mixer machine in order to obtain uniform dispersion of the
ingredients within the vehicle.
30. ☆ Antioxidants :
An antioxidant is a substance which is used to prevent the
oxidative degradation of the drug in the presence of oxygen or
peroxides.
Any preparation containing aqueous phase are very much
susceptible to oxidation. As suspension contains aqueous phase,
a suitable antioxidants should be added to the suspension
formulation to prevent oxidation of the preparation.
Widely used antioxidants:
BHA, BHT, Citric acid, tartaric acid, EDTA salts.
31. ☆ Preservatives
Preservatives are substances that commonly added to
pharmaceutical products to prevent or inhibit the growth of
microorganisms in the preparations in order to prolong their shelf
life.
Widely used preservatives:
BHA, BHT, Parabens, Benzoic acid, Na Benzoate, alcohol, phenol.
▪ Sweetening agents
They are employed in suspension to mask the unpleasant taste of
drugs & to increase the palatability of the preparation.
▪ Example : Sucrose, lactose, glucose, sorbitol, mannitol, saccharin
etc.
32. ☆ Flocculating agents :
Flocculating agents defined as the substances that can be added to
the medium of a suspension to promote flocculation by causing
colloids & other suspended particles to aggregate,forming a floc.
Example : Na lauryl sulphate, tragacanth, alginates,electrolytes.
☆ Surfactants :
Surfactants are the substance that reduce the surface tension of
the liquid in suspension , thereby increasing its spreading and
wetting agent properties.
Examples : Na lauryl sulphate, K laurate
33. ☆ Wetting agent
The agents that are added to the formulation of a suspension in order
to reduce the interfacial tension between the drug particles & the
vehicle & thus allowing the particles to disperse more easily , is called
wetting agent.
Some solids are not easily wetted by the liquid & tend to clump &
because of the strong interfacial tension . Thus these particles are not
readily dispersed throughout the vehicle. Such drugs are called
hydrophobic drugs.
To ensure adequate wetting and dispersion of these drugs, wetting
agent are added to the suspension.
Widely used wetting agents: Surfactants , Hydrophilic colloid &
Solvents
34. ☆ Flavouring agents
Flavouring agents are used to suspension to give a pleasant smell &
cover the pungent smell in the preparation, Thus make the product
more palatable & improve patient acceptance.
They must be used in small quantities. Widely used flavouring
agents are- Rosemary , orange, cherry, pine-apple & vanilla flavour.
☆ Coloring agents
They are used to impart a distinctive appearance to the suspension
& make it attractive.
Only FDA approved coloring agents are used like TiO2, Carmine,
Saffron.
35. Evaluation of suspension preparation
After manufacturing of a suspension, the suspension must be
evaluated-
For the identification of the stability.
For the determination of the potency.
For the determination of the activity.
For the determination of purity.
The evaluation of suspension include-
1. Chemical evaluation
2. Physical evaluation
36. ☆ Chemical evaluation
After formulation, a suspension is stored for about six months & then
its active
ingredients as well as excipients are assayed. At the same time, a
newly formulated suspension is assayed & is compared with the
previous formulation. If the amount of active ingredient & excipients
of both suspension are same, then the previous formulation said to be
chemically stable.
☆ Physical Evaluation
For physical evaluation of suspension, the following tests are
performed-
Ease of redispersion ; Colour, flavour & taste ; pH adjustment; Purity.
37. Problems associated with suspension preparation
☆ Cap locking :
• Causes : It's a filling problem which occurs when the dispersed
particles crystallize on the threads of the bottle cap.
• Remedy : It can be prevented by using different vehicles containing
sucrose, glucose, sorbitol & glycerine.
☆ Dispersion of hydrophobic drugs :
• Causes : Hydrophobic drug particles don't dissolve in water. So,
suspension of hydrophobic drugs creates problem in particle dispersion.
• Remedy : By adding wetting or surfactants which can promote the
dispersion of hydrophobic drug molecules in water
38. ☆ Chemical interaction:
• Causes : Chemical interaction may be occurred during the addition of
additives to the drug such as cationic surfactants react with any anionic
ingredients.
• Remedy: Care should be taken when additive added to the drug.
☆ pH change :
• Causes : Drug degradation ; Alakalinity of glass bottle ; Microbial
growth.
• Remedy : By adding buffering agents that help to maintain chemical
stability also ensure physiological compatibility.
☆ Color change :
• Causes : Light sensitive color may be changed in presence of light. Due
to increase in surface area, some color may be changed.
• Remedy : By using the bottle in dark place or using light protective
bottles.
39. ☆ Microbial growth :
• Causes : Most suspensions almost in neutral pH & susceptible to
microbial growth.
• Remedy : By adding preservatives or antioxidants.
☆ Crystal growth :
• Causes : There is always a degree of crystal growth which mainly
occurs in storage condition due to-
Temperature fluctuation, pH change, Low solubility & Impurity.
• Remedy: By preventing temperature fluctuation, By Controlling pH , By
controlling solubility & By adding surfactants.
☆ Change in particle size :
• Causes : Sometimes particle size may be increased which results in rapid
settling.
• Remedy : By using viscosity imparting agents.
