This presentation related to Coarse dispersion includes suspension

1. Coarse Dispersion
Presented By:
Ms. Sarika S. Suryawanshi
Associate Professor
M. Pharm (Pharmaceutics)
Ashokrao Mane College of Pharmacy, Peth Vadgaon

3. • Coarse dispersion is heterogeneous , biphasic systems
which contains dispersed phase particles or globules
having range above colloidal size.
• Suspension in which finely divided solid is dispersed in
continuous phase of solid, liq, gas.
• undissolved solids exists in equilibrium with saturated
solution of solid in continuous phase.
• It contains particles having range 1 nm to 0.5 µm called
colloidal suspension.
• Range 1-100 µm called coarse suspension.

4. • Interfacial properties of suspended particles:
• Rate of sedimentation depends on
• Particle size , density of particle & vehicle, viscosity of
medium. Stocke’s law
• v = d2 (s - o) g/18 o d = the diameter of the
particle in cm.
• s = the density of the dispersed phase (particles).
• o = the density of the dispersed medium.
• g = the acceleration due to gravity
•  = the viscosity of the dispersion medium in poise.

5. • Velocity of particles in suspension is reduced by decreasing
the particle size & minimizing difference between densities
of particles & vehicle.
• Since density of particle is constant for substance & can not
be changed.
• Sedimentation depends on viscosity of vehicle.
• Limitations of stoke’s equation: for conc of dispersed phase
it applies only spherical particles in dil suspension 0.5-2 %.
• Particles must be freely settle without collision.
• Should not have any physical / chemical attraction with
medium.
• Physical stability depends on mean particle diameter &
particle size distribution of suspended insoluble drug.
• Lower limit of coarse suspension is particles large than
0.1µm.

6. • Sedimentation parameters:
• Sedimentation volume:
• Ratio of final volume of sediment to original volume of
sediment before settling.
• F= Vu/V0
• F= Hu/ H0 for measuring cylinder H height.
• Sedimentation volume range less than 1 to greater than 1.
• F is less than 1.
• 0.76 means 76%
• Sedimentation volume for deflocculated suspension:
• FD= VD/V0
• Sedimentation volume is relatively small.
• It is measured for quality control.

7. • 2 Degree of flocculation (β):
• useful for comparing different suspension formulation in
terms of flocculation.
• β =F/FD
• = Vu/V0 / VD/V0
• = Vu/VD
• Ultimate sediment volume of flocculated suspension/
Ultimate sediment volume of deflocculated suspension
• Increase in volume of sediment is due to flocculation.

8. • Sedimentation Velocity :
• Velocity of particle in unit centrifugal force expressed by
Swedberg coefficient
• S= dx/dt/ W2X
• dx/dt- sedimentation rate
• W- angular velocity
• X- distance of particle from center of rotation
• On application of centrifugal force, particle passes from
position X1 at time t1 to position X2 at time t2 under such
condition Swedberg coefficient
• S= In (X2/X1)/ W2(t2-t1)

9. • Factors affecting on sedimentation
• Particle Size diameter
• sedimentation Velocity (V) directly proportional to
square of diameter of particle
• Good suspension have reduced particle size to half of its
original size so decreases rate of sedimentation.
• Extreme particle size – hard cake
• Density Differences:
• sedimentation velocity directly proportional to density
difference between dispersed phase & medium
• Density of solid is greater than medium
• Both are equal rate of settling become zero
• Density of medium can be increased by exciepients

10. • Viscosity of dispersion medium
• sedimentation velocity inversely proportional to
viscosity of dispersion medium
• V α 1/n
• Good dispersion, viscosity of medium increased
by decreasing particle setting
• Greater viscosity gives problem like pouring
redispersibility so it should maintain
• Greater viscosity inhibits crystal growth, prevent
transformation of metastable crystal to stable
crystal & enhance physical stability
• Limitation for viscosity: redispersibility, retard
absorption, problem during handling mfg

11. • Brownian motion
• Drunken walk of particle
• Velocity, density,
• 2-5 micron
• Flocculation
• Defloculated suspension larger settle easily
• Clear boundary can not observe
• Flocculated flocs settles fast
• Clear boundary

12. • Interfacial properties of solids:
• Physical stability of suspension means particles do not
settle down, do not formation of hard cake.
• Solid must remains suspended long enough time for
accurate dose to be poured out for administration.
• Settling create problem when sediment is not easily &
uniformly redispersed.
• Solid particle must remains unchanged in size & form.
• Crystal growth leads changes in particle size, solid to solid,
polymorphic, amorphous to crystalline can change form of
particle.
• No physical changes in ingredients of suspension.

13. • Particles should dispersed medium of suspension.
• Can be achieved by size reduction of dispersed phase
material up to 5µm shows Brownian motion.
• Size reduction increase surface free energy of particles &
makes system thermodynamically unstable.
• To get stable state , reduce surface free energy.
• Thus increase surface area & reduce interfacial tension
are used to maintain stability of suspension.

14. • Particle - particle interaction:
• Aggregation accelerates the sedimentation & affect on
redispersibility.
• Aggregation affect on controlling rate .. DLVO theory
• Interaction of two charged particles which gives
flocculated & deflocculated suspension.
• From curve attractive potential is predominant at short
distance of separation.
• At larger distance separation there is secondary
minimum.
• If this slightly larger than kinetic energy particle may be
aggregates & form loose cluster.

15. • In deflocculated system particles dispersed & carry infinite
charge on their surfaces form repulsive force when approach
one another.
• These forces prevents aggregation of the particle but after
sedimentation form close pack arrangement with smaller
particle fills void space between large particles further lower
portion of sediment get pressed by weight of sediment.
• Once repulsive force barrier is overcome then particles come
closer to each other & establish strong attractive force.
• leads to formation of hard cake in deflocculated system.

16. • Redispersion is difficult, sufficient force is required to
separate the particles & develop high energy barrier
between them.
• In flocculated system particles remains in secondary
minimum i.e particles are not able to overcome the high
potential barrier therefore they remains closely attached
with each other.
• Particle with high energy barrier & they are easily
redispersed.
• This system is apparent stable than flocculated system
which achieves long term stability.
• Electrolytes reduces repulsive forces of particles by
decreasing zeta potential & formation of bridge between
adjacent particle to link them together in loosely packed
structure.

17. • Surface free energy:
• Thermodynamically stable system possess low Surface
free energy.
• Reduction in particle size leads to increase in Surface free
energy (ΔG) which related to surface area
• Input of energy via mechanical agitation, triturating
particle size reduced increasing interfacial area (ΔA)
with increasing surface free energy
• ΔG= ƔSl ΔA
• ƔSl= interfacial tension between Solid & liq
• Due to high SFE system is thermodynamically unstable
• Reduce SFE by decreasing surface area (agglomeration) ,
SFE= 0 by reducing interfacial tension by addition of
wetting agent

18. • Formulation of suspension:
• 1. flocculated suspension:
• Formation of floc or aggregation of particle in flocculated
suspension cause increase in sedimentation rate due to
increase in size of sedimenting particle.
• Also porosity plays an imp role in sedimentation.
• In flocculated suspension loose structure of rapidly
sedimenting flocs tend to preserve in the sediment, which
contains required amount of liquid.
• Volume of sediment is relatively large so redispersed easily.

19. • Deflocculated suspension:
• Individual particles settles so rate of sedimentation is very
slow which prevents entrapment of liq medium called
cracking or claying.
• On storage for some time claying occurs then difficult to
redisperse by agitation.
• Large particles settles faster while smaller particles remains
supernant liquid which appears cloudy.
• Particles carry charge on surface, when particles are closer
they experience repulsive force which creates high
potential barrier so it prevents formation of flocs .
• This can be observe in deflocculated suspension at primary
minimum when rate of sedimentation is slow.

21. • Flocculated suspension formulation
• Flocculated system consists of dispersed phase in the
form of large fluffy agglomerates.
• Flocculation refers to loose aggregation of particles
held together in network like str stable floc
containing varying amount of entrapped liquid .
• Stable state (C) may be reached either directly by
wetting of dispersed hydrophobic particle (A) with
suitable flocculating surfactant or indirectly by
wetting to produce dispersed or peptized particles
(B) then flocculating with hydrocollioids.
• Stable Flocculated suspension resuspended by
agitation.
• As size of floc increases rapid rate of sedimentation

22. • Over flocculation leads to aggregation (E) due to addition
of higher amount of suspending agents or storage at
elevated temp
• Unstable .. Irreversible
• Absence of protective colloid crystal growth begins (D) to
form crystals
• Rate of sedimentation depends on size of flocs &
porosity
• Decrease in floc formation Decreases SFE between
particle & medium leads to thermodynamically stable
system
• Control on flocs by optimum conc of electrolyes , SAA,
polymers
• Change in conc flocculated to deflocculated state

23. • A. floc formation
• flocs formation on addition of electrolyes , SAA,
polymers, some liquids
• Electrical barrier between particle is decreased by
electrolytes which bring them together to form
floccules
• Due to bridge between adjacent particle
• Eg: Bismuth sub nitrate dispersed in water based on
electrophoretic mobility potential due to strong force
of repulsion between adjacent particles, it was
observed that system gets peptized or deflocculated

24. • Bismuth sub nitrate suspension with increased conc
of monobasic pot phosphate causes positive zeta
potential to decrease due to adsorption of negatively
charged phosphate anion.
• further addition zeta potential falls to zero then
increase in negative direction
• When zeta potential become sufficiently negative
sedimentation volume star to fall which is manifested
from low sedimentation volume.

25. • Controlled flocculation of bismuth ions .. Flocculating
power of electrolytes increases with valency of ions
• Cal ions more powerful to attempt flocculation than
sodium ions because valency of calcium is two
whereas sodium has valency one
• Ionic non ionic surfactant used to bring flocculation
• Optimum conc imp , it acts as wetting agent
• Conc decreases SFE by reducing surface tension
form closely packed agglomerates
• Less SFE particles attracted with each other by van
der Waals forces & form loose aggregation

26. B) Structured vehicles
• Structured vehicles are vehicles containing thixotropic
compounds/polymers like acacia which are pseudo-
plastic or plastic in nature.
• Thixotropic compounds/polymers form a three-
dimensional gel network structure which entrap the
particles so that, ideally, no settling occurs.
• During shaking the gel network is completely
destroyed (pseudoplastic and plastic in nature) so that
administration is facilitated

28. • Electro kinetic Properties
• Nernst Potential
• Nernst potential or reversal potential is the potential
across a cell membrane that opposes the net
diffusion of a particular ion through the membrane.
• zeta potential is the potential difference between
the dispersion medium and the stationary layer of
the fluid attached to the dispersed particle of the
colloidal dispersion.
• Flocculated suspension has zeta potential -20 to +20
mv
• ZP of charged Affected by suspending agent as dec in
ZP cause aggreagation

29. • Instability in suspension
• Particle size leads to caking
• Enlargement of particle size on storage leads to crystal
growth
• When drug material is in dispersed phase, small particle
will have higher solubility results in conc gradient
between drug solution & solid particle
• High drug conc found at surrounding of larger particles,
this follows Fick’s law of diffusion where small particles
diffuses
• Causes drug conc decreases around small particle & vice
versa leads to crystal growth in large particle & drug is
crystallized
• Thus smaller particle small & vice versa.. Oswald
Ripening

30. • Result in unstable suspension & alter availability by
altering dissolution rate.
• Oswalds ripening problem can be minimized by
addition of polymer , cellulose derivatives
• Uniformity in particles
• Higher temp increases solubility & dissolved particles
move towards large particles when temp drop &
crystallization occurs.

31. • Evaluation of suspension
• Appearance, colour, odour, taste, pH
• Sedimentation behavior – sedimentation volume,
degree of flocculation
• Redispersiability
• Rheological behavior used to determine settling
behavior & arrangement of vehicle & particle
• Structure of suspension changes during storage
• Structural changes evaluated by rheological method
• Viscosity