Coarse dispersion, flocculated and deflocculated suspension, Stability of suspension, DLVO Theory

1. COARSE DISPERSIONS
- SUSPENSIONS
- EMULSIONS
School of Pharmacy
G H Raisoni University, Saikheda.

2. SUSPENSIONS
Suspensions containing finely divided drug
distributed somewhat uniformly throughout a
vehicle in which the drug exhibits a minimum
degree of solubility.
A pharmaceutical suspension is a coarse
dispersion in which insoluble solid particles are
dispersed in a liquid medium.
The particles have diameters for the most part
greater than 0.1 µm,

3. Some suspensions are available in ready-to-use form, that is,
already distributed through a liquid vehicle with or without
stabilizers and otheradditives.
Other preparations are available as dry powders intended for
suspension in liquid vehicles.
Generally, this type of product is a powder mixture containing
the drug and suitable suspending and dispersing agents to be
diluted and agitated with a specified quantity of vehicle, most
often purified water(reconstitution).
Drugs that are unstable if maintained for extended periods in
the presence of an aqueous vehicle (e.g., many antibiotic drugs)
are most frequently supplied as dry powder mixtures for
reconstitution at the time of dispensing.

4. REASONS FOR SUSPENSIONS
certain drugs are chemically unstable in solution
but stable when suspended. In this instance, the
suspension ensures chemical stability while
permitting liquid therapy.
This is particularly advantageous for infants,
children, and the elderly.
preparing a palatable liquid dosage form: The
disadvantage of a disagreeable taste of certain
drugs in solution form is overcome when the drug
is administered as undissolved particles of an oral
suspension.

5. For example, erythromycin estolate is a less
water-soluble ester form of erythromycin and
is used to prepare a palatable liquid dosage
form of erythromycin, the result being
Erythromycin Estolate Oral Suspension,
USP.
For the most part, oral suspensions are
aqueous preparations with the vehicle
flavored and sweetened to suit the
anticipated taste preferences of the intended
patient.

6. 1. Should be therapeutic active , chemically / physically stable, and1. Should be therapeutic active , chemically / physically stable, and
esthetic appeal.esthetic appeal.
2. Must remain sufficiently homogeneous for at least the period of time2. Must remain sufficiently homogeneous for at least the period of time
necessary to remove and administer the required dose afternecessary to remove and administer the required dose after
shaking.shaking.
3. A properly prepared pharmaceutical suspension should settle slowly3. A properly prepared pharmaceutical suspension should settle slowly
and should be readily redispersed upon gentleand should be readily redispersed upon gentle containercontainer shaking .shaking .
4. The particles which settle to the bottom of the container must not4. The particles which settle to the bottom of the container must not
form a hard cake.form a hard cake.
5. The particle size of the suspended particles should remain fairly5. The particle size of the suspended particles should remain fairly
constant throughout long periods of undisturbed standing.constant throughout long periods of undisturbed standing.
6. The suspension should pour readily and evenly from its container.6. The suspension should pour readily and evenly from its container.
FEATURES DESIRED IN A
PHARMACEUTICAL SUSPENSION

7. SEDIMENTATION RATE OF THE
PARTICLES OF A SUSPENSION
The various factors involved in the rate of settling of the particles of a
suspension are included in the equation of Stokes law,

8. Stokes law

9. A number of factors can be adjusted to enhance the physical stability
of a suspension, including the diameter of the particles and the
density and viscosity of the medium.
Greater the density of the particles, the greater the rate of
sedimentation
Because aqueous vehicles are used in pharmaceutical oral
suspensions, the density of the particles is generally
greaterthan that of the vehicle, a desirable feature.
If the particles were less dense than the vehicle, they
would tend to float and floating particles would be quite
difficult to distribute uniformly in the vehicle.

10. The rate of sedimentation may be appreciably
reduced by increasing the viscosity of the
dispersion medium,
However, a product having too high a viscosity
is not generally desirable, because it pours with
difficulty and it is equally difficult to
redispersed
Therefore, if the viscosity of a suspension is
increased, it is done so only to a modest extent

11. The viscosity characteristics of a suspension
may be altered by:
the vehicle used,
the solids content. As the proportion of solid
particles in a suspension increases, so does the
viscosity.
Suspending agents, viscosity enhancers.

12. Suspending agents : agents employed to thicken
the dispersion medium and help suspend the
particles.
Carboxymethylcellulose (CMC),
methylcellulose,
microcrystalline cellulose,
polyvinylpyrrolidone,
xanthan gum,
bentonite

13. When polymeric substances and hydrophilic colloids
are used as suspending agents, appropriate tests
must be performed to show that the agent does not
interfere with availability of the drug.
These materials can bind certain medicinal agents,
rendering them unavailable or only slowly available
fortherapeutic function.
Also, the amount of the suspending agent must not
be such to render the suspension too viscous to
agitate (to distribute the particles) orto pour.

14. TYPES OF SUSPENSION
Flocculated Suspensions:Flocculated Suspensions:
•Suspension in which particles are weakly bonded, settle rapidly.Suspension in which particles are weakly bonded, settle rapidly.
•Flocs are light, fluffy conglomerates which are held together by weakFlocs are light, fluffy conglomerates which are held together by weak
wander waals forces of attraction.wander waals forces of attraction.
•Do not form a cake and are easily resuspended with a minimum ofDo not form a cake and are easily resuspended with a minimum of
agitation.agitation.
•These suspension have better physical stability but less bioavailability.These suspension have better physical stability but less bioavailability.
Deflocculated Suspension:Deflocculated Suspension:
•Suspension in which particles settle slowly, and eventually form aSuspension in which particles settle slowly, and eventually form a
sediment in which aggregation occurs with the resultant formation of a hardsediment in which aggregation occurs with the resultant formation of a hard
cake which is difficult to resuspended.cake which is difficult to resuspended.
•These suspension have shorter half life but greater bioavailability.These suspension have shorter half life but greater bioavailability.

15. flocculated
Suspension
Deflocculated
Suspension

16. INTERFACIAL PROPERTIES OF SUSPENDED
PARTICLES
An acceptable suspension should not exhibit settling of dispersed
solids.
This can be achieved by reducing the particle size to a level of 5
microns so that they exhibit Brownian motion.

17. Since size reduction implies that work (W) has to
be done to divide large particles to smaller
particles, this process can be written as-
W= ∆G- γSL x ∆A
∆G- Increase in surface free energy
γSL- Interfacial tension between liquid medium & solid particles
∆A- Increase in Surface area of interface due to size reduction.

18. Two approaches are possible to regain stability-
1.∆A may be reduced to zero, so that ∆G will become
zero, this is possible by regrouping the particles to form
aggregates or flocs.
2. Interfacial tension γSL may be reduced so that the
system can be stabilize, but cannot be made zero, as
dispersed particles have certain positive interfacial
tension. Surface active agent are added to reduce this
tension to a minimum.

19. Settling/Sedimentation in different systems
In flocculated systems:
The flocs tend to fall together (fast sedimentation due to large
size)
A distinct boundary between the sediment and the supernatant.
The liquid above the sediment is clear because even the small
particles present in the system are associated with the flocs

20. In deflocculated systems (with a range of particle
sizes):
In accordance with Stokes' law, the larger particles sediment
more rapidly than the smaller particles.
No clear boundary is formed (unless 1 particle size is present)
The supernatant remains turbid for a longer period of time.

21. Deflocculated system
(a) Within a few minutes of manufacture there is no apparent change
within the deflocculated system compared to its initial appearance.
(b) Even after several hours there is still little obvious change, except
that the concentration of solids in the lower layers has increased at
the expense of the upper layers owing to slow particle
sedimentation. There is a small amount of a compact sediment.
(c) After prolonged storage , depending on the physical stability of the
system, the supernatant has cleared, leaving a compact sediment.
Flocculated system
(a) There is some clear supernatant with a distinct boundary between
it and the sediment.
(b) After several hours there is a larger volume of clear supernatant
with a relatively large volume of a porous sediment, which does
not change further even after prolonged storage (c).

22. clear supernatant
clear supernatant
clear supernatant

23. SupernatantSupernatant
RedispersibilityRedispersibility
SedimentSediment
RheologyRheology
ViscosityViscosity
SuspensionSuspension
BoundaryBoundary
Velocity ofVelocity of
sedimentationsedimentation
SedimentedSedimented
particleparticle
DeflocculatedDeflocculatedFlocculatedFlocculated
Forms a network likeForms a network like
structurestructure
FastFast
fall togetherfall together
a distinct boundarya distinct boundary
between sediment andbetween sediment and
supernatantsupernatant
clearclear
Separate ndividualSeparate ndividual
particlesparticles
slowslow
fall according to sizefall according to size
no distinct boundaryno distinct boundary
between sediment andbetween sediment and
supernatantsupernatant
turbidturbid
HighHigh LowLow
plastic &plastic &
pseudoplasticpseudoplastic
DilatentDilatent
Loosely packed andLoosely packed and
doesn’t form a cakedoesn’t form a cake
DifficultDifficultEasyEasy
Closely packed andClosely packed and
form a hard cakeform a hard cake
Not pleasing in appearanceNot pleasing in appearance Pleasing inPleasing in
appearanceappearance

24. INGREDIENTS of SUSPENSIONINGREDIENTS of SUSPENSION
I -I - Insoluble drug.Insoluble drug.
II- Vehicle (suspending medium).II- Vehicle (suspending medium).
III- Wetting agents.III- Wetting agents.
IV- Compounds allowing control of stability andIV- Compounds allowing control of stability and
sedimentation (Flocculating, Suspending agent)sedimentation (Flocculating, Suspending agent)
V - Additives used to regulate the flow behavior.V - Additives used to regulate the flow behavior.
VI- pH regulatorsVI- pH regulators
VII- Other additives ( flavour, colour, taste preservatives).VII- Other additives ( flavour, colour, taste preservatives).

25. Approached used in the formulation of suspension

26. Particles
Addition of wetting agent & dispersion medium
Uniform dispersion of deflocculated particles
A
Incorporation of
Structured vehicle
B
Addition of
flocculating agent
C
Addition of
flocculating agent
Deflocculated suspension
in structured vehicle
as final product
Flocculated suspension
as final product
Flocculated
suspension
Incorporation of
Structured vehicle
Flocculated suspension
in structured vehicle
as a final product
Fig. Flocculated suspension as final product

27. Structured vehicles-Deflocculated suspensions
Structured vehicles:
• Structured vehicles are vehicles which exhibit Pseudoplastic
or plastic rheologic behavior.
• Also they should possess some degree of thixotropic
behavior (gel- sol-gel transformation), such a behavior
improves the physical stability of suspensions.
• Structured vehicles are extensively used to prepare
deflocculated suspensions.
• Stoke’s law is applicable.
• They are prepared using hydrocolloids.
• Desired conc. Of suspension depends upon- Viscosity,
Amount of solid, Particle size, Density of solids

28. Controlled flocculation-Flocculated suspensions
Different approaches used to achieve flocculation:
a. Most dispersed particles possess a surface charge.
The intensity of this charge can be reduced by the
addition of agents with an opposite charge
(electrolytes). As a result , Zeta potential decreases
and particles establish attractive forces between
adjacent particles.
a. Surfactants and polymers are long chain compounds.
These substances act by adsorbing a part of chains on
the particle surface and projecting out the remaining
part into the medium. This type of bridging promotes
the formation of flocs.

29. Electrolytes:
Effect of electrolytes on the flocculation of a suspension is given below-
Examples:
1.Effect of electrolyte (Flocculating agent)- Aluminium Chloride on Bismuth subnitrate
suspension
2.Effect of electrolyte (Flocculating agent)- Monobasic Pot. Phosphate on
Sulfamerazine suspension.

30. Surfactants:
•They improve thedispersion by reducing the interfacial tension.
•They also act as wetting agents and deflocculationg agents.
•In ionic surfactants, head portions adsorb on the solid surface and the tails project
outwards & form bridges between the particles.
•Non-ionic surfactants such as Tweens assume partial negative charge in aqueous
dispersion and from network like structure between particles.
Polymers:
Act as flocculating agents because a part of the polymer chain projecting out
into the dispersion medium.

31. THE SEQUENCE OF STEPS INVOLVED IN THE FORMATION OF A STABLE SUSPENSION
Flocculation in structured vehicles:

32. Zeta potential is therefore a function of the surfaceis therefore a function of the surface
charge of the particle. Because it reflects the effectivecharge of the particle. Because it reflects the effective
charge on the particles and is thereforecharge on the particles and is therefore related to therelated to the
electrostatic repulsionelectrostatic repulsion between them, the zeta potentialbetween them, the zeta potential
has confirmed to be extremely related to the colloidalhas confirmed to be extremely related to the colloidal
stability and maintains colloidal dispersion.stability and maintains colloidal dispersion.