Dispersion system suspensions interfacial properties of suspensions zeta potential Sedimentation parameters Settling in suspension Formulation of suspension Preparation of suspension

1. COARSE
DISPERSION
● Suspensions
● Emulsions
NABEELA MOOSAKUTTY
ASST.PROFESSOR
DEPT. OF PHARMACEUTICS
KTN COLLEGE OF PHARMACY

2. COARSE
DISPERSION
2
● Heterogenous dispersion
● Size range of dispersed
particles
1 μm to 100 μm

3. Dispersed System
Internal phase (Dispersed)
External phase (Continuous phase)

4. The internal phase consisting of insoluble solid
particles having a range of size (0.5 to 5 microns)
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
4

5. SUSPENSIONS
Definition
Heterogenous system in which
solid particles (dispersed phase)
is uniformly dispersed in liquid
medium (continuous phase)
5

6. “ Coarse Suspension
Particle size > 1 mm
Colloidal Suspension
Particle size < 1 mm
Pharmaceutical Suspension
Contains therapeutically active
particles
6

7. Why we are using suspensions
When drug is not soluble in vehicle
Ex: Prednisolone Suspension
Taste of drug: Bitter / Unpleasant
Ex: Chloramphenicol palmitate suspension
Enhancement of Chemical stability
Ex: Procaine Penicillin G
Sustained or Controlled release
Protamine-Zinc Insulin Suspension
7

8. Ideal Characteristics
The suspended molecules should not settle rapidly
They must be easily re-suspended by moderate shaking
It should be easy to pour
It should be free from grittiness
It should have pleasant odour, colour and palatability
It should be easily flow out from syringe needle
It should be physically,chemically and microbiologically stable
8

9. Interfacial properties of suspended particles
▪ The interface is formed in between the two phases, which influence the stability of
suspension
▪ While formulating suspensions, solid particles reduced to fine particles then, disperse
them in a continuous medium
9
System with fine particles [thermodynamically unstable]
Having large surface area and excess of surface free energy
Particles become highly energetic
Tend to regroup [ In order to decrease the total area and surface free energy]
ΔG = γ . ∆A [ΔG=surface free energy, ∆A=total surface area, γ=interfacial tension]
Formation of floccules Formation of aggregates / compacted cake

10. System become
thermodynamically
stable
When the surface free
energy (∆G) equals to
zero
10
This can be achieved by adding wetting agents or
surfactants to the suspension this results in
reduction of interfacial tension and interfacial area

11. Formation of Electric Double Layer
▪ If a particle have a size >1 nm is
dispersed in water, there will be a
reaction between at the solid-
liquid interface
▪ Both solid and liquid parts carry
different energy levels
11
▪ Basically, all substances intrinsically carry a negative surface
charge once they are dispersed in water [caused by the high
dielectric constant of water

12. ▪ Media with a lower dielectric constant
carry anionic surface charge
▪ Water contains ions of dissolved salts
and get attracted by the surface
charge, Thus these ions gather around
the particle
▪ A well-loaded and immovable layer
covers the surface of the particle. This
is the Stationary Layer / Stern Layer 12

13. ▪ The remaining ionic charges attracts
surrounding cations from the surrounding
water to the surface of the particles
▪ The second layer develops around the particles
and it is away from the particle surface
▪ The attractive force of anionic charges get
weaker with the distance, it is less loaded and
movable. This is the Diffuse Layer
13
● The boundary line between the stationary and diffuse ions is the
Shear Plane
● The potential at this boundary line is called Stern potential /
Streaming potential
● Cationic ions neutralizes the anionic surface charge
● They cannot neutralize the surface charge completely

14. ZETA POTENTIAL
The total charge that exist on suspended
particles is the zeta potential or The potential
at the Slipping line [boundary line of diffuse
layer] is called zeta potential
If zeta potential is high,
● Repulsive forces will be more than attractive forces
● Particles remain dispersed and deflocculated
Zeta potential can be reduced by adding electrolytes
● At particular conc. Of electrolytes,
attractive forces dominates slightly over the repulsive force
Particles form loose aggregates and remains flocculated
● At large conc. Of electrolytes particles get deflocculated again

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POTENTIAL
ENERGY
CURVE
Primary maximum
Particle
Particle
Attraction curve
Repulsion curve
Energy curve for flocculated suspension
Potential energy as a function of interparticle distance

16. DLVO THEORY
They assumed that when the particles
are dispersed in a liquid medium the
y will have
Repulsive forces [Vr]
(zeta potential)
+
Attractive forces [Va]
(Van Der Waal)
Overall interaction
[Vt]
Derjaguin
Landau
Verwey
Overbeek

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20. Deflocculated Suspension
When particles approach each other they experience repulsive forces
Creates high potential barrier
Prevents the aggregation of particles
Primary maximum - sedimentation of particles very slow
Particles forms a close packing arrangement
[smaller particles fills the voids btw the larger particles]
Lower portion of the sediment get pressed by the weight of the sediment
above [This force is sufficient to overcome the high energy barrier]
Once this energy barrier is crossed, particles come in close contact with
each other and establish stronger attraction forces
Formation of hard cake
20
SETTLING
IN
SUSPENSION

21. Flocculated Suspension
▪ Particles reside at secondary
minimum
▪ Particles are separated by
about 1000 to 2000 Å
▪ Particles are loosely
structured
▪ Easily redispersible
21

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SETTLING IN SUSPENSION
Stoke’s Law : The settling kinetics in a dispersed system - Proposed by George Gabriel Stokes

23. v = The rate of settling of suspended particles in cm/sec
d = Diameter of the particle in cm
ρs = Density of the dispersed phase g/cm³
ρo = Density of the dispersion medium g/cm³
ηo = Viscosity of the dispersion medium in poise
g = Acceleration due to gravity 23
Sedimentation rate is directly proportional to the radius of the
particles, gravity and density difference between the dispersed
phase and dispersion medium and inversely proportional to the
viscosity of the dispersion medium
Applicable only for diluted pharmaceutical suspensions ( 0.5 - 2% solids/100ml)
Particles should be Spherical

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Alexander et al 1990
Stoke’s law is cannot be applied in Pharmaceutical suspension because of
● Particles are largely irregular shape
● Most suspensions contain dispersed solids in concentrations of 5 to 10% or higher
leads to hindered settling (Particles interfere with the free settling of other
particles)
Modified Stoke’s law
V’ = VƐⁿ
V’ = Corrected rate of settling
Ɛ = Initial porosity of the system
[Initial volume fraction of the uniformly mixed suspension]
n = measure of the hindering of the system

25. Factors affecting particle settling
(sedimentation)
25
1. Particle shape
● It determines the packing arrangements and thereby influences the stability and
resuspendability of the suspension
● Ex: Symmetrical barrel shaped particles of calcium carbonate produce stable suspension without
caking upon storage whereas asymmetrical needle shaped particles formed hard cake
2. Brownian movement
● It prevents sedimentation
● It depends on 2 factors Particle size and Viscosity
● It shows when particle size in the range of 2 to 5 micrometer
3. Particle size
● Smaller particles yield a low rate of sedimentation
● Reducing the particle size to extreme degree of fineness leads to aggregation of particles

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4. Viscosity of the medium
● Higher the viscosity lower is the rate of sedimentation
● It can be enhanced by viscosity increasing agents (Ex: methyl cellulose, HPMC, acacia
and Tragacanth) which reduce the rate of settling
5. Density of the medium
● The difference in density between the dispersed phase and dispersion medium
affect the rate of settling
● If the density of the medium equals to the density of solids, the rate of settling
become zero it means no sedimentation
● Density of the medium can be increased by density modifiers Ex: sorbitol, mannitol

27. Sedimentation Parameters
27
They are used to determine the extent of sedimentation
1. Sedimentation Volume
2. Degree of flocculation
Sedimentation Volume (F)
It is the ratio of ultimate volume of the sediment (Vu) to the actual volume of sediment (Vo) before
settling
F = Vu / Vo
The value of F gives the Physical stability of the suspension
F = 1 : no sedimentation no clear supernatant
F = 0.5 : 50% of the total volume is occupied by sediment
F > 1 : sediment volume is greater than the actual volume due to formation of network of floccules

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Degree of flocculation
It is the ratio of sedimentation volume of flocculated suspension (F) to the sedimentation volume of
deflocculated suspension (Fa)
β = F / Fa
β = 1 represent deflocculated suspension
β > 1 represent flocculated suspension (greater will be the stability)

29. Formulation of Suspension
29
3
Approaches
1. Dispersion of solids
2. Use of Controlled flocculation
3. Flocculation in structured vehicle

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1. Dispersion of solids
Dispersion process means intimate contact of the solids with water as vehicle
Critical and difficult step (most solids hydrophobic in nature)
In the case of finely divided powders they adsorb or entrap a lot of air and
float on the surface of the vehicle
The dispersion of solids in a vehicle (water) can be achieved by the use of
1. Water miscible co-solvents
2. Wetting agents (Surfactants)
3. Use of structured vehicles - Deflocculated suspensions
Water miscible co-solvents
Ex: Alcohol, glycerin, propylene glycol etc

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Wetting agents (Surfactants)
● Aids in dispersion by reducing the interfacial tension between the
solid particles and the vehicle
● Contact angle is lowered and air is displaced from the surface of the
solids
● Surfactants in the HLB range of 7-9 are used as wetting agents
● Minimum amount of surfactant is used because they produce foam
Contact angle 90°- float
Contact angle 0°- complete wetting
Contact angle 180°- insignificant wetting

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Use of structured vehicles
● These are made up of hydrocolloids
Advantages
1. These get hydrated well in water, swell to a great degree
and produce high viscosity at a low concentration
2. Act as protective colloids and stabilize charges
● These possess some degree of thixotropic behaviour (gel-
sol-gel) improves physical stability of suspension
● Examples: MC, HPMC, Sodium CMC, Carbopol and
Bentonite

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Use of Controlled flocculation
Flocculating agents
1. Electrolytes
2. Surfactants
3. Polymers
Electrolytes
Most dispersed particles possess a surface charge. The intensity of this charge can
be reduced by the addition of electrolytes (with opposite charge)
Zeta potential decreases and particle establish attractive forces between adjacent
particles
Ex: Dispersion of bismuth subnitrate in water

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The effects of electrolytes on the flocculation of a suspension

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Bismuth subnitrate dispersed in water - Experiences a large positive charge (zeta potential)
System becomes deflocculated
Addition of flocculating agent Monobasic potassium phosphate in small quantities
The negatively charged phosphate ions get adsorbed on the positively charged bismuth particles
Then the repulsive forces decrease and attractive forces begin to operate
Zeta potential decreases solids begin to form flocs
Further addition of electrolytes zeta potential decreases and becomes zero - suspended particles
remain as flocs
On further addition of electrolytes, dispersed particles acquire a negative charge (due to excess
adsorption of phosphate ions)
Once again particles experiences repulsive forces - suspension changes to deflocculation state
Now the system have negative zeta potential
Achieving controlled flocculation of positively charged solids

38. Surfactants
38
● These are acting by reducing surface tension
● Capable of acting as wetting and deflocculating agents
● Concentration of surfactant is critical in achieving flocculation
● The ionic surfactants, the head portion adsorbs on the solid surface and the tail
project outwards and form bridges between particles, such an arrangement brings
flocculation and prevents precipitation of solids
● Ex: Sodium lauryl sulphate

39. Polymers
39
● These are acting as flocculating agents
● A part of the polymer chain get adsorbed on the particle surface
with the remaining portion projecting out into the dispersion
medium
● Ex: Xanthan gum
Flocs formation by polymer bridging

40. Flocculation in structured vehicles
40
● In a flocculated suspension, the
supernatant becomes clear rapidly - This is
an undesirable property
● By the application of principles of both
flocculation and structured vehicles we
could get improved suspension
● The flocculating agents facilitates the
formation of aggregates of uniform size
● The structured vehicles prevent these
aggregates (flocs) from settling
● Ex: Carboxymethylcellulose, carbopol 934,
Tragacanth, Bentonite

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Suspending agents /
Structured vehicles /
Thickening agents
Hydrocolloids form colloidal dispersion with water and increase the
viscosity of the continuous phase
Acacia, Tragacanth, Sodium alginate,
MC, CMC, Bentonite
Wetting agents Used for dispersion of solids in continuous liquid phase
Conc. used: less than 0.5%
Ionic and Non-ionic surfactants
Flocculating agents Formation of flocs by reducing zeta potential of charged particles in
suspension
Aluminium chloride
Monobasic potassium phosphate
Buffers Maintain pH of desired range Acetates, Citrates
Osmotic agents Produce osmotic pressure comparable to biological fluids ( ophthalmic
and injectable preparations)
Dextrose, mannitol and sorbitol
Preservatives Prevent microbial growth Benzoic acid (0.1%) Propylene glycol (5-
10%)
Colouring and Flavouring
agent
To Increase Patient Acceptance Colouring: Brilliant blue
Flavouring: Anise oil
Humectants Prevent degradation of API by adsorbing moisture Propylene glycol, Glycerol
Co-solvents Liquid penetrates in individual particle and facilitates wetting Alcohol, Glycerin, Polyethylene glycol

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PREPARATION
OF
SUSPENSION

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