3. Brief introduction and definition
Advantages
Types
Classification on different basis
Criterias for suspensions
Evaluation of suspension
Formulation of suspension
Preparation techniques
Comparison of flocculated and deflocculated
4. A system in which one substance (The
Dispersed Phase) is distributed, in discrete
units, throughout a second substance (the
continuous Phase).
Coarse dispersions are of 2 types:
1-Suspensions
2-Emulsions
5. Suspensions are heterogeneous biphasic
thermodynamically unstable coarse
dispersion system in which internal phase
is dispersed uniformly throughout the
external phase with the aid of single or
combination of suspending agents.
particle size of internal phase ranges
between 10 – 15 micrometer.
For example, Paracetamol suspension,
insulin zinc suspension.
6. To increase solubility of insoluble drug
To mask bitter taste of drug e.g
chloramphenicol palmitate
To increase drug chemical stability e.g.
Procaine penicillin G
To achieve controlled/sustained drug
release.
They exhibit higher rate of bioavailability
than capsule and tablets.
16. 12- Vaccines
• e.g. Cholera vaccine
13- X-ray contrast agent
• e.g. Barium sulphate for examination of
alimentary tract
17. Suspensions can be classified on the basis of:
Mode of dispensing
Concentration
Particle size
Sediments
18. There are 2 types of suspensions:
Extemporaneous suspensions
Reconstituted suspensions
19. Such suspensions are prepared just before
dispensing to the patients;
• who are unable to swallow solid dosage
forms ( tablet and capsules) e.g. infants
• When no other liquid dosage form is
available.
USP designs these suspensions as
“ORAL SUSPENSIONS”
20. They have high specificity regarding addition
of suspending agent, storage and labeling.
For example: Pediatric antibiotic
suspensions , rifadin suspensions
21. These are powders or granules which are
intended to be suspended in water or some
other vehicle prior to oral administration
In USP these are designated as:
“FOR ORAL SUSPENSION”
For example:
• tetracycline suspension and barium sulphate
for oral suspension.
22. There are 2 types of suspensions:
• Dilute suspensions
• Concentrated suspensions
23. “ Such suspensions in which
concentration of solid particles ranges from 2
to 10% w/v solid”
For example: cortisone acetate suspension,
prednisolone acetate suspension.
24. “Such suspensions in which
concentration of solid particles is 50%w/v”
For example:
• zinc oxide suspension
25. There are 3 types of suspensions:
Colloidal suspensions
Coarse suspensions
Nano suspensions
26. COLLOIDAL
SUSPENSIONS
• Suspensions having particle size of
dispersed solid less than about 1 micron
COARSE
SUSPENSIONS
• Suspensions having particle size of
dispersed phase greater than 1 micron
NANO
SUSPENSIONS
• These suspensions are biphasic colloidal
dispersions of nano sized drug particles
stabilized by surfactants. Size of dispersed
phase is less than 1 micrometre.
27. On the basis of sedimentation, there are 2
types of suspensions:
• Flocculated suspensions
• Deflocculated suspensions
28. In these suspensions, there is a formation of
light, fluffy group of particles held together
by weak vander waals forces.
29. In these suspensions, solids are present as
individual particles, they exhibit aggregation
but comparatively low than flocculated
suspensions.
30. A well-formulated suspension should have:
Easy and readily redispersion of sedimented
particles , important for uniformity of dose
No cake formation on setting
Viscosity optimum for pouring
Physical, chemical and microbiological
stability
Pleasing odor, colour and palatability
Free from gritting particles( in case of
suspensions for external use)
32. Suspensions are evaluated by determining their
physical stability, methods inlude:
Sedimentation method
Rheological method
Electro kinetic method
Micromeritic method
33. Sedimentation of particles in a suspension is
governed by several factors:
• particle size
• density of the particles
• density of the vehicle
• viscosity of the vehicle
The velocity of sedimentation of particles in
a suspension can be determined by using the
Stoke's law.
34. Where:
v = velocity of sedimentation
d = diameter of the particle
g = acceleration of gravity
p1 = density of the particle
p2 = density of the vehicle
η = viscosity of disperse medium in poise
v =
d2 (p1-p2) g
18
v =
d2 (p1-p2) g
18
35. Two parameters are studied for
determination of sedimentation
Sedimentation volume
Degree of flocculation
36. Sedimentation volume is a ratio of the
ultimate volume of sediment (Vu) to the
original volume of sediment (VO) before
settling
F = V u / VO
Where:
• Vu = final or ultimate volume of sediment
• VO = original volume of suspension before
settling
37. F has values ranging from less than one to
greater than one
• When F < 1 Vu < Vo
• When F =1 Vu = Vo
• When F > 1 Vu > Vo
Sediment volume is greater than the original
volume due to the network of flocs formed in
the suspension and so loose and fluffy
sediment
38. It is the ratio of the sedimentation volume of
the flocculated suspension ,F , to the
sedimentation volume of the deflocculated
suspension, F∞
ß = F / F∞
• F =(Vu/Vo) deflocculated
• F∞ = Vu/Vo) deflocculated
The minimum value of ß is 1,when
flocculated suspension sedimentation volume
is equal to the sedimentation volume of
deflocculated suspension.
39. Solid particles can get charged by:
• Selective adsoption of ions at surface
• Ionization of functional group of dispersed
phase
Two type of electrical potential cotribute to
electrokinetic properties of suspensions:
Nernst potential
Zeta Potential
The flocculated suspension is one in which
zeta potential of particle is -20 to +20 mV.
40. • The difference in electric
potential between the
actual surface of the
particle and the
electroneutral region is
referred to as Nernst
potential.
Nernst
potential
• The zeta potential is
defined as the difference
in potential between the
surface of the tightly
bound layer (shear plane)
and electro-neutral
region of the solution.
Zeta
Potential
44. The viscosity of the suspension is studied at
different time intervals by using a good
quality of viscometer, it gives useful
information about the stability of suspensions
45. Stability of suspension depends upon the
particle size of the dispersed phase
Any change in particle size with reference to
time will provide useful information
regarding the stability of a suspension
46. Three approaches are commonly involved:
Use of structured vehicle
Use of controlled flocculation
Combination of both of the methods
47. Thickening or suspending agents.
They are aqueous solutions of natural and
synthetic gums.
These are used to increase the viscosity of
the suspension.
It is applicable only to deflocculated
suspensions
Entrapped the particle and reduces the
sedimentation of particles.
E.g. methyl cellulose,sodium carboxy methyl
cellulose, acacia, gelatin and tragacanth
48. Controlled flocculation of particles is
obtained by adding flocculating agents,
which are:
electrolytes ( bismuth subnitrate, monobasic
pot. Phosphate)
surfactants (ionic and nonionic)
polymers
49. Sometimes suspending agents can be added
to flocculated suspension to retard
sedimentation
Examples of these agents are:
Carboxymethylcellulose (CMC),
Carbopol 934,
Veegum, and bentonite
50.
51. Work by increasing viscosity of liquid
vehicle, and slowing down settling in
accordance to Stokes Law, these agents
mainly prevents caking at the base of any
suspentions. Suspending agent form film
around particle and decrease interparticle
attraction.
Most suspending agents perform two
functions
• besides acting as a suspending agent
• they also imparts viscosity to the solution
52. SUSPENSIONS
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
methylcellulose
3-11 1-2%
CMC 7-9 1-2%
Colloidal
silicon dioxide
0-7.5 2- 4 %
Stability pH range and concentrations of most commonly used suspending agents.
52
54. Two main formation methods are used:
Precipitation methods:
Dispersion method:
55. Three main methods
Organic solvent precipitation
Precipitation effected by changing pH of the
medium
Double decomposition
56. Water insoluble drugs
Dissolve in organic solvents
Add organic phase to water
organic solvents include ethanol, methanol,
propylene glycol and polyethylene glycol.
57. Applicable to those drugs in which solubility
is dependent on pH value.
Concentrated solution in favorable pH
pour to other system to change pH
On agitation precipitate will form
E.g estradiol suspension.
58. Two water soluble reagent forms a water
insoluble product.
Eg white lotion NF
Zinc sulphate solution
Solution of sulphurated potash
Precipitate of zinc polysulphide
59. Vehicle is formulated
solid phase is wetted and dispersed
use of surfactant to ensure wetting of
hydrophobic solids
60. Small scale preparation of suspensions
Large scale preparation of suspensions
61. Grinding the insoluble materials with a vehicle
containing the wetting agent.
soluble ingredients are dissolved in same
portion of the vehicle
Added to the smooth paste to step1 to get
slurry.
Make up the dispersion to the final volume
62.
63. If suspension is made by dispersion process it
is best to achieve pulverization of solid by
micronization technique or spray drying
If suspension is made by controlled
crystallization, a supersaturated solution
should be formed and then quickly cooled
with rapid stirring.
64.
65. Floculated suspension Defloculated suspension
Particles forms loose
aggregates and form
flock
Rate of sedimentation is
high
Particles exist as
separate entities form a
cake
Rate of sedimentation is
slow
66. Floculated defloculated
Sediment is rapidly
formed
Sediment is loosely
packed and doesn’t
form a hard cake
Sediment is easy to re
disperse
Suspension is not
pleasing in appearance
The floccules stick to
the sides of the bottle
Supernatant formed is
clear
Sediment is slowly
formed
Sediment is very closely
packed and a hard cake
is formed
Sediment is difficult to
re disperse
Suspension is pleasing in
appearance
They don’t stick to the
sides of the bottle
Cloudy supernatant
67. Floculated defloculated
Sediment is rapidly
formed
Sediment is loosely
packed and doesn’t
form a hard cake
Sediment is easy to re
disperse
Suspension is not
pleasing in appearance
The floccules stick to
the sides of the bottle
Supernatant formed is
clear
Sediment is slowly
formed
Sediment is very closely
packed and a hard cake
is formed
Sediment is difficult to
re disperse
Suspension is pleasing in
appearance
They don’t stick to the
sides of the bottle
Cloudy supernatant