Pharmaceutical Suspension, Coarse dispersion, Classification of dispersions, properties of coarse, colloidal and molecular dispersions Thermodynamic and kinetic stability of dispersed systems Electric Properties of Interfaces: Nernst and zeta potential, effect of electrolytes Suspensions: DLVO theory, flocculated and deflocculated systems, controlled flocculation, physical stability of suspensions

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

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

3. 33
WHY WE ARE USING SUSPENSIONS?

4. 44
➢ The suspended particles should not settle rapidly and sediment produced, must
be easily re-suspended by the use of moderate amount of shaking.
➢ It should be easy to pour yet not watery and no grittiness.
➢ It should have pleasing odour , colour and palatability.
➢ Good syringeability.
➢ It should be physically,chemically and microbiologically stable.
➢ 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
➢ A pharmaceutical suspension is a coarse dispersion in
which internal phase (therapeutically active ingredient)
is dispersed uniformly throughout the external phase.

9. 9
➢ 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.
➢ 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. Thermodynamic stability of
dispersed systems
• Large surface area of solid particles of dispersed
phase that results from comminution (size
reduction) is associated with surface free energy
that makes the system thermodynamically unstable.
• Therefore, particles tends to regroup to reduce
total surface area thereby reducing surface free
energy
• Particles in suspension tends to flocculate by weak
Van der Waal forces, may form agglomerate
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13. Thermodynamic stability of
dispersed systems
• Surface free energy (ΔG) in suspension
• ΔG =γSL ΔA
• γSL is interfacial tension
• Approaches for stable emulsion
• Reduce γSL by adding surface active agent
• Reduce ΔA by controlled flocculation
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14. Kinetic stability of dispersed
systems
Theory of Sedimentation
• 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
1414

15. • 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
15

16. 16
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)
➢ Particles which freely settle without collision .
➢ Particles with no physical or chemical attraction.

17. 1717
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

18. 1818
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

19. 1919
The sedimentation volume gives qualitative account of
flocculation.

20. 2020
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.

22. 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. 2222
.

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Electric double layer

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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
• Adsorb 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 (next figure)
• First layer is aa' to bb'
• Second layer is bb' to cc'... more negative charge is present
in this layer in this case.

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

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

27. 2828
➢ 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
➢The flocculated suspension is one in which zeta potential
of particle is -20 to +20 mV
➢ Thus the phenomenon of flocculation and
deflocculation depends on zeta potential carried by
particles.
Zeta potential

28. 30
30
In flocculated suspension, formed flocs (loose aggregates) will
cause increase in sedimentation rate due to increase in size of
sedimenting particles.
➢ Hence, flocculated suspensions sediment more rapidly.
➢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. 3131
Deflocculated suspensions
➢In deflocculated suspension, individual particles are
settling.
➢ Rate of sedimentation is slow , which prevents
entrapping of liquid medium which makes it difficult to
re-disperse by agitation.
➢This phenomenon called ‘caking’ or ‘claying’.
➢ 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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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 (hard
cake) 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
adjacent 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
• Hydrophilic polymer act as protective colloids
• 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 changes particle size distribution
in suspension.
• Particle growth is common if solubility is
temperature dependent.
• When temperature is high, small particles
dissolve to form saturated solution.
• When temperature decreases, solute deposit
on large crystals hence → crystal size increases
for large size crystals

44. Particle size distribution
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Oswald ripening
• Oswald ripening can be reduced by adding
polymer or surfactant
• Polymer (PVP) segment adsorb on drug (e.g.
acetaminophen)
• Hydration sheath present around polymer
molecule
• Polymer inhibit approach of drug molecule
from solution to crystal surface for deposition
• High molecular wt. polymer (PVA) are more
effective

46. Fig. Dissolution and
crystallization
of drug in
presence of
polymer
2019/4/17

47. 2019/4/17
Effect of excipients on suspension stability
• Flocculation by sorbitol depend cloud point
• Stability of suspension decrease because of
interaction with excipients
• If low cloud point surfactant (low solubility) is
used then less amount of sorbitol is needed to
induce flocculation
• (Cloud point is the temperature above which
an aqueous solution of a water-soluble
surfactant becomes turbid)
• Amount of preservative (Benzalkonium Cl )
can change zeta potential

48. References
• P. J. Sinko, ‘Martin’s Physical Pharmacy and
Pharmaceutical Sciences’ Fifth edition, Lippincott
Williams and Wilkins, Indian Edition distributed by
B.I. Publications Pvt. Ltd, 2006
• Textbook of Physical Pharmaceutics, C.V.S
Subrahmanyum, Vallabh Prakashan
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