Suspension, DLVO theory

1. Coarse Dispersion
(Dr.) Mirza Salman Baig
Assistant Professor (Pharmaceutics)
AIKTC, School of Pharmacy,New Panvel
Affiliated to University of Mumbai (INDIA)

2. 2
Ø Definition.
Ø Classification.
Ø Theoretic consideration of
suspensions
Ø Formulation of suspensions
•Sedimentation
•Brownian movement
•Electrokinetic properties
CONTENTS

3. 33
WHY WE ARE USING SUSPENSIONS?

4. 44
Ø The suspended particles should not settle rapidly and
sediment produced, must be easily re-suspended by the use
of moderate amount of shaking.
Ø It should be easy to pour yet not watery and no grittiness.
Ø It should have pleasing odour , colour and palatability.
Ø Good syringeability.
Ø It should be physically,chemically and microbiologically
stable.
Ø Parenteral /Ophthalmic suspension should be sterilizable.
Features Desired In Pharmaceutical
Suspensions

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WHAT ARE SUSPENSIONS?

6. 6
• The term "Disperse System" refers
to a system in which one substance
(The Dispersed Phase) is
distributed, in discrete units,
throughout a second substance (the
continuous Phase ).
• Suspensions are heterogenous
system consisting of 2 phases.
6
DISPERSE SYSTEM

7. 77
A solid in liquid dispersion, in which the
particle size is more than colloidal size.
DISPERSE SYSTEM
DISPERSION MEDIUM DISPERSED PHASE
oAqueous / oily liquid oInsoluble solid

8. 88
Definition
Ø A Pharmaceutical suspension is a coarse dispersion in
which internal phase (therapeutically active
ingredient)is dispersed uniformly throughout the
external phase.

9. 9
Ø The internal phase consisting of
insoluble solid particles having a range
of size(0.5 to 5 microns) which is
maintained uniformly through out the
suspending vehicle with aid of single
or combination of suspending agent.
Ø The external phase (suspending
medium) is generally aqueous in some
instance, may be an organic or oily
liquid for non oral use.
9

10. 10
Classification
•Based particle size of dispersed
phase
Coarse dispersion
Collidal dispersion
Molecular dispersion
• Based On Electrokinetic Nature Of
Solid Particles
Flocculated suspension
Deflocculated suspension

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Classification of dispersed system
based on particle size

12. 12
Theory of Suspensions
• Sedimentation Behaviour
• Sedimentation means settling of particle or
floccules under gravitational force in liquid
dosage form.
• Brownian motion
• Velocity of sedimentation expressed by
Stokes Equation
12

13. • Where, vsed. = sedimentation velocity in cm / sec
• d = diameter of particle
• ρ s= density of disperse phase
• ρ o= density of disperse media
• g = acceleration due to gravity
• η = viscosity of disperse medium in poise
Stokes Equation
13

14. 14
Limitation of Stoke’s Equation .
Stoke's equation applies only to:
Spherical particles in a very dilute suspension
(0.5 to 2 gm per 100 ml)
Ø Particles which freely settle without collision .
Ø Particles with no physical or chemical
attraction.

15. 1515
Sedimentation Parameters
Sedimentation volume (F) or height (H)
for flocculated suspensions:
Definition:
Sedimentation volume is a ratio of the ultimate
volume of sediment (Vu) to the original volume
of suspension (Vo) before settling.
F = Vu / Vo
Where,
Vu = final or ultimate volume of sediment
Vo = original volume of suspension before settling

16. 1616
F has values ranging from less than one to greater
than one.
When F < 1 Vu < Vo
When F =1 Vu = Vo
The system (F =1) is said to be in flocculation
equilibrium and show no clear supernatant on
standing.
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 and extra vehicle is
needed (added) to contain sediment

17. 1717
The sedimentation volume gives qualitative
account of flocculation.

18. 1818
Degree of flocculation (β)
"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∞
(Vu/Vo) flocculated
ß = --------------------
(V∞/Vo) deflocculated
Vu
ß = ------
V∞

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Degree of flocculation
Note: The minimum value of ß is
1,when flocculated suspension
sedimentation volume is equal to
the sedimentation volume of
deflocculated suspension.

20. 2020
.
Thermodynamic and kinetic stability of
dispersed systems
Brownian Movement
Brownian movement of particle prevents sedimentation
by keeping the dispersed material in random motion.
Brownian movement depends on the density of
dispersed phase and the density and viscosity of
the disperse medium.
The kinetic bombardment of the particles by the
molecules of the suspending medium will keep the
particles suspending,
Particle size is below critical radius (r) for brownian
movement.

21. 2121
Electrical Properties of Interfaces

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Electrical Properties of Interfaces:
Electric double layer
• Consider solid surface in contact with solution of electrolyte
containing ions
• Some cations (+) adsorb on solid surface
• Adsorbe ions that give charge to surface aa' (in this case
cations +) known as potential determining ions.
• Anions attracted to positive charge by electrical force of
attraction known as counter ions or gegenions .
• Shear plane is bb' rather than aa' because of tightly bound
layer
• First layer is aa' to bb'
• Second layer is bb' to cc'... more negative chargr is present
in this layer in this case.

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Electric double layer

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Nerst potential
• Potential at solid surface due to aa'
due to potential determining ions is
known as nerst potential
• It is define as potential difference
between actual surface and electro
nutral region

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Zeta potential
Ø 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.
Ø Zeta potential has practical
application in stability of systems
containing dispersed particles .

26. 2626
Ø If the zeta potential is reduced below a certain
value, the attractive forces exceed the repulsive
forces, and the particles come together. This
phenomenon is known as flocculation
Ø The flocculated suspension is one in which zeta
potential of particle is -20 to +20 mV
Ø Thus the phenomenon of flocculation and
deflocculation depends on zeta potential carried
by particles.
Zeta potential

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Electrokinetic potential

28. 28
28
In flocculated suspension, formed flocs (loose
aggregates) will cause increase in sedimentation
rate due to increase in size of sedimenting particles.
Ø Hence, flocculated suspensions sediment more
rapidly.
Ø Here, the sedimentation depends not only on the
size of the flocs but also on the porosity of flocs.
Deflocculation and flocculation
(Flocculated Suspensions)

29. 2929
Deflocculated suspensions
Ø In deflocculated suspension, individual
particles are settling.
Ø Rate of sedimentation is slow , which
prevents entrapping of liquid medium which
makes it difficult to re-disperse by agitation.
Ø This phenomenon called ‘caking’ or
‘claying’.
Ø In deflocculated suspension larger particles
settle fast and smaller remain in supernatant
liquid so supernatant appears cloudy.

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DLVO theory
• DLVO theory was developed in
the 1940s and named after the
• Russian scientists
– B. Derjaguin
– L. Landau,
• Dutch scientists
– E. Verwey
– J. Overbeek),

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DLVO
• It proposed that an energy barrier resulting from
the electrostatic repulsive force prevents two
particles approaching one another and adhering
together.
• If the particles collide with sufficient energy to
overcome the barrier, the Van der Waals attractive
force will attract them strongly and cause
them adhere together irreversibly.
• If the particles repel each other strongly, the
dispersion will resist coagulation and the
dispersed system will be stable.
• If the repulsion is not sufficient then coagulation will
take place.

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Contd...

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Flocculation curve/Secondary minimum

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Need of Controlled Flocculation
• Assume powder is properly wetted
and dispersed
• In order to prevent compact
sediment we need controlled
flocculation

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Controlled Flocculation
• Electrolytes (ionic substance) act as
flocculating agents by reducing
electrical barrier between particles...
by decresing zeta potential and
forming bridge between adjascent
particles
• Surfactant
• Polymer

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• At low electrolyte
conc --Repulsive
force predominate
• At high electrolyte
conc --Repulsive
force reduce and
cause coagulation
Effect of electrolytes

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Bismuth subnitrate suspension

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Effect of electrolytes
• Bismuth sub nitrate particles posses
+ve charge
• If we add monobasic potassium
phosphate (KH2PO4) then positive
zeta potential decrease to zero
because of adsorption of -ve
phosphate ions then increase in
negative direction
• At certain +ve zeta potential,
maximum flocculation occur

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Effect of electrolytes
• Onset of flocculation coincide with
maximum sedimentation volume
• When zeta potential become
sufficiently -ve repeptization
(deflocculation) occur once again and
sedimentation volume(F) falls

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Effect of Surfactant
• Surfactant improve dispersion by
reducing surface tension
• Act as wetting and deflocculating
agent
• Ionic surfactant (SLS) sometime
cause flocculation

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Effect of Polymers
• Act as flocculating agent
• Chain of polymer adsorb on multiple
particles
• Ex. Xanthum gum

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Physical stability of suspensions
• Raising temperature leads to
flocculation of sterically stabilized (by
non ionic surfactant) suspension
• Repulsion force depend upon amount
of surfactant adsorbed on particles
• On heating energy of repulsion
reduces because of dehydration of
surfactant, attraction increases and
particles flocculate

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Physical stability of suspensions
• During freezing processes particle
overcome repulsive barrier due to ice
formation.
• Particles come close enough and
experience attractive force like in
primary minimum and form
aggregates as per DLVO theory

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Oswald ripening
• Fluctuation in temperature changes
particle size distribution in
suspension.
• Particle growth is common if solubility
is temperature dependant.
• When temperature is high, small
particles dissolve to form saturated
solution.
• When temperature reduces solute
deposit on large crystals hence crystal
size increases for large size crystals

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Oswald ripening
• Oswald ripenning can be reduced by
adding polymer or surfactant
• Polymer (PVP) segment adsorb on
drug (acetaminophen)
• Hydration sheeth present around
polymer molecule
• Polymer inhibit approach of drug
molecule from solution to crystal
surface for deposition

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Excipients
• Stability of suspension decrease
because of interaction with
excipients
• If low cloud point surfactant is used
then less amount of sorbitol is
needed to induce flocculation
• Amount of preservative
(Benzalkonium Cl ) can change zeta
potential