PHYSICAL PHARMACEUTICS II COARSE DISPERSION

COARSE DISPERSION
R.VIJAYAKUMAR ., M Pharm.,
Assistant Professor ,
Department of Pharmaceutics,
Velallar College of Pharmacy,
Erode-52

SUSPENSIONS
 Suspensions are the biphasic liquid dosage form of
medicaments in which the finely divided solid
particles.
 The range of solid particles in suspension from 0.5 to
5.0 micron.
 Suspensions are used in orally, parentally and also
externally.
 They are chemically stable than solution.
R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

 According to the particle size of the dispersed phase,
suspensions are divided into:
 Coarse suspension:
which is a dispersion of particles with a mean
diameter greater than 1 µm.
 Colloidal suspension:
Which is a dispersion of particles with a
mean diameter less than 1 µm
Erode-12

Advantages of suspension
If patient has a difficulty of swallowing solid dosage
forms (a need for oral liquid dosage form).
Faster rate of dissolution and oral absorption than solid
dosage forms, yet slower than solutions.
Drugs that have very low solubility are usefully
formulated as suspensions.
Drugs that have an unpleasant taste in their soluble
forms (e.g., chloramphenicol (soluble) vs.
chloramphenicol palmitate (insoluble ))
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Ideal properties of suspension
Suspension should settle slowly & should be readily
redispersed upon shaking of the container.
The suspension is pourable.
Particles in suspension are small and relatively
uniform in size.
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Classification
Based on General class (administration)
→ Oral Suspension e.g. Paracetamol
Suspension
→Externally Applied suspension e.g. Calamine
lotion
→ Parenteral Suspension e.g. Insulin zinc
suspension
R.Vijayakumar M Phram., Asst Professor,VCP Erode-12

Based on proportion of Solid Particles
Dilute Suspension (2 to 10% w/v solid)
e.g. cortisone acetate, predinsolone acetate
Concentrated Suspension (50% w/v solid)
e.g. Zinc oxide suspension
Based on electrokinetic nature of Solid particle
 Flocculated Suspension
 Deflocculated Suspension
Erode-12

Based on Size of Particle
Coarse Suspension
Suspensions having particle sizes of greater
than about 1micron in diameter are called as coarse
suspensions.
Colloidal Suspension
Suspensions having particle sizes of
suspended solid less than about 1micron in size are
called as colloidal suspensions.
Erode-12

Interfacial Properties
when the interfacial properties between the solid phase and
the liquid are considered:
 Surface free energy increase resulting from increase in
surface area of suspended particles due to reduction in size
of particles
 Presence of electrical charges on the surface of the
dispersed solid particles in a liquid medium. The increase in
surface free energy due to a reduction in size of the
particles is given by the relation: ∆G = γ ∆A
Where ∆G = increase in surface free energy in ergs,
∆A = increase in surface area in cm2,
γ = interfacial tension in dynes/cm
Erode-12

 Electrical Properties at the surface of the dispersed particles
 Both attraction and repulsion forces exist between particles
dispersed in a liquid medium.
 The particle-particle interaction (due to attraction and
repulsion) may be given as follows.
The various electrostatic contributions:
 They may be ion-ion, ion- dipole, dipole-dipole and dipole-
induced dipole.
 They have both attractive (between dissimilar charges) and
repulsive forces (between similar charges) The London
dispersion forces (between atoms of one particle with those
of the other).
 It is induced dipole-induced dipole interaction (attraction)
The covalent bonds (attractive) Born repulsion forces
(repulsive).
 It is due to overlapping of electron clouds of the atoms
present in a molecule or ion.
Erode-12

 The region in which the influence of the surface charge
(i.e. potential) of the particle is appreciable is termed
the electric double layer region.
 The electric double layer is considered to comprise:
 The Stern layer consisting of counter ions: The
thickness is of the ionic dimension. The potential drop
across the stern layer from the surface of the particle is
sharp.
 The diffuse double layer: The potential drop across this
layer is somewhat gradual and it drops to zero at the
end of its surface where it meets electroneutral region.
Erode-12

Flocculation and De-flocculation
in suspensions.
The overall (or resultant) charge
existing on the suspended
particle is called as zeta potential
and it is a measurable indication
of the charge.
Therefore,
flocculation and
deflocculation may
be considered in
terms of zeta
potential.
When the zeta potential is high, the
particles remain dispersed and are
said to be deflocculated.
These particles
resist collision due
to the high zeta
potential even if the
particles are
brought close by
way of random
motion or
agitation.
governed
by Zeta
potential
Erode-12

Erode-12

Methods in Formulation of Suspension
 Suspension Containing Diffusible Solids
 Suspension Containing Indiffusible Solids
 Suspension Containing Poorly Wettable Solids
 Suspension Produced by Chemical Reaction
Erode-12

Formulation of Suspension
Flocculation and De-flocculation in suspension
Erode-12

Settling in Suspension
Settling of particle (or) floccules occur under
gravitational force in liquid dosage form resulting in
Sedimentation.
The sedimentation velocity of particles in suspension is
related to
size of the particles
Density of the particles
Viscosity of the dispersion medium
Velocity of sedimentation expressed by
Stokes Equation
Erode-12

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 poiseR.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

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.
Erode-12

Sedimentation Parameters
 Sedimentation volume (F) or Height (H)
(flocculated suspensions)
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
Erode-12

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∞
ß = (Vu /Vo ) flocculated / (V∞/Vo ) deflocculated
ß = (V∞/Vo )
Erode-12

Stability in suspension
 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. Brownian movement can be
observed,
If particle size is about 2 to 5µm,
 When the density of particle & viscosity of medium are
favorable.
Erode-12

Electro kinetic properties
Zeta Potential
The zeta potential defined as the difference between
the surface of the tightly bound layer (shear plane) &
the electroneutral region of the solution.
Erode-12

An is a thermodynamically unstable
system containing mixture of two or more immiscible
liquids which is stabilized by adding emulsifying agent.
Erode-12

The diameters of the
globules usually vary from
0.1 to 10 µm, although
globule diameters as small
as 0.01 µm and as large as
100 µm are possible in
some emulsions.
Emulsions having globules
of mean diameter about 5
µm are called fine
emulsions and emulsions
with large globules are
referred to as coarse
emulsions.
The emulsion is
thermodynamically unstable
since the globules coalesce
and the phases will
ultimately separate. To
stabilize an emulsion, a third
substance called emulgent
or emulsifier or emulsifying
agent is invariably added to
the emulsion.
The emulsion may be a
dilute dispersion, a
concentrated dispersion or
semisolid. The liquid
emulsions are opaque,
milky white, and viscous.
The semisolid emulsions
are called creams.
Erode-12

TYPES OF EMULSION
Oil -in-Water
type emulsion
O/W
Water-in-oil
type emulsion
W/O
Multiple
emulsion or
complex
emulsions
W/O/W
O/W/O
Micro
emulsions
Based on size of liquid droplets:
➢ 0.2 – 50 mm → Macroemulsions
➢ 0.01 – 0.2 mm → Microemulsions
Erode-12

Applications of Emulsion
Erode-12

Emulsions afford
protection to
drugs
susceptible to
oxidation or
hydrolysis.
Liquid paraffin is
used as
purgative when
taken orally and
is not absorbed.
It should not be
made into fine
emulsion since
fine globules
may be
absorbed.
Some enemas
are made as
emulsions either
for local action
(E.g. soap
enemas) or to
influence drug
action. Solid
drugs which
show poor
solubility may be
dissolved in the
oil and
emulsified.
From this
emulsion, the
bio-availability is
more (as
compared to
tablet or
suspension.
E.g.. non-
steroidal
antifungal
agents).
Erode-12

Theories of Emulsification
Erode-12

Viscosity theory
As per this theory, an increase in viscosity of an
emulsion will lead to an increase in stability.
This theory failed to explain about the milk which
shows considerable stability even though its viscosity is
less.
Erode-12

Film theory
 Film theory or Adsorption theory
 As per this theory, the added emulsifying agent forms a
mechanical film by getting adsorbed at the interface of
the liquids (i.e. at the interface between the dispersed
globules and the dispersion medium {o/w}) and offers
stability to the emulsion.
 However, this theory could not explain the formation of
type of emulsion.
Erode-12

Wedge theory
According to this theory, monovalent soaps like
sodium stearate give o/w type emulsion and divalent
soaps like calcium stearate give w/o type emulsion.
This was explained by the successful accommodation
of the, soaps at the interface and subsequent possible
orientation of the soap molecules to give the type of
emulsion.
For example,
sodium stearate may
be represented as
follows, R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Interfacial tension theory
Thus there is no universal theory of emulsification.
Any theory, to be meaningful, should be capable of explaining
(a) type of emulsion formed
(b) stability of emulsion
In accordance with this theory the added emulsifying
agent reduces the interfacial tension between the oil
and water phases and thus a stable emulsion is formed.
This theory could not explain the formation of type
of emulsion.
Erode-12

Test for identification of emulsion type (O/W , W/O)
Dilution test
(miscibility
test)
Staining test
(dye solubility
test)
Conductivity
measurement
Fluorescence
test
Erode-12

Preparation of Emulsions: Small scale
method
Mortar and pestle method
 It is used for emulsions which are stabilized by a
multimolecular film at the interface.
 Consequently the emulgents used are acacia, tragacanth,
agar, cellulose derivatives, etc.
 There are two basic methods (wet gum method and dry
gum method) for the preparation of such emulsions.
 The emulsions produced show polydisperse globules with
wide range of sizesR.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Wet Gum Method
 In this the emulgent is placed in the mortar and dispersed in
water to form mucilage.
 The oil is added in small amounts with continuous
trituration, each portion of the oil is emulsified before
adding the next increment.
 The optimum ratio of fixed oil; water and acacia is 4:2:1 to
prepare initial emulsion called primary emulsion. The ratio
of volatile oil, water and gum is 3:2:1.
 The ratio varies with emulgents. The primary emulsion
should be triturated at least for five minutes.
 Then sufficient water is added to produce the final volume.R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Dry Gum Method
 In this, the gum is added to the oil and dispersed in a
mortar and pestle.
 The water is added in little quantities at a time with
trituration to produce the primary emulsion.
 Preparations of emulsions by wet gum method and dry
gum method may be carried out by shaking or agitation
in bottles rather than in a mortar and pestle.
Erode-12

Emulsifying Agents
 When one liquid is broken in large no. of small globules
then interfacial area increases.
 Interfacial energy associated with interface also increases.
 To reduce interfacial energy, globules of dispersed phase
tends to coalesce (merge)
 To prevent coalescence and to keep system stable in
disperse state it is necessary to add emulsifying agent
 Reduction of interfacial tension leads to Thermodynamic
stabilization
 Formation of interfacial film barrier between the globules
(Mechanical barrier to coalescence )
 Formation of electric double layer by the Electrical barrier
to approach of stable globules.R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Emulsifying Agents/emulgents
 Emulsifying agent prevent coalescence of globules of
disperse by forming film around globules.
 An emulsifying agent is any material that enhances the
stability of an emulsion
 Emulsifying agents can be divided into 3 groups
1. Surfactants (Surface active agents)
2. Hydrocolloids
3. Finely divided solids
Erode-12

HLB
 systemic decisions about the amounts and types of
surfactants needed in stable products.
 The system is called the HLB (hydrophile lipophile
balance) system and has an arbitrary scale of 1 - 18.
 HLB numbers are experimentally determined for the
different emulsifiers.
HLB value & Application
1 - 3
3 – 6
7 - 9
8 - 13
13 -15
15 -18
Anti-foaming agent.
W/O emulsifying agents.
Wetting agents.
O/W emulsifying agents.
Detergents.
Solubilizing AgentsR.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Surfactants (Surface active agents)
Anionic surfactants:
These are organic salts which, in water, have a surface-active anion.
 E.g. Alkali metal and ammonium soaps (salts of long chain fatty
acids) such as sodium stearate and potassium oleate (o/w).
 Soaps of divalent and trivalent metals such as calcium oleate (w/o).
 Amine and ammonium soaps such as triethanolamine oleate (o/w).
 Alkyl sulphates such as sodium lauryl sulphate (SLS) (o/w).
Disadvantages:
 They are irritant internally so widely used in external preparations as
o/w emulsifying agents.
 Anionic surfactants are generally stable at more alkaline pH.
Erode-12

Cationic surfactants
 These are usually quaternary ammonium compounds
which have a surface-active cation.
 Examples include cetrimide and benzalkonium chloride.
 They are used in the preparation of o/w emulsions for
external use and must be in their ionized form to be
effective.
 The cationic surfactants also have antimicrobial activity.
Disadvantages:
 They are sensitive to anionic surfactants and drugs.
 Emulsions formed by a cationic surfactant are generally
stable at acidic pH.
 They are more toxic than other surfactants.
Erode-12

Hydrocolloids
 Natural Polysaccharides:
Acacia, Tragacanth ,starch, pectin.
 Semi-synthetic polysaccharides:
These are derived from the naturally occurring
polysaccharide cellulose and generally form o/w emulsions.
Methylcellulose (MC)
Carboxymethylcellulose (CMC)
Hydroxypropylmethylcellulose (HPMC),
 Synthetic hydrocolloids:
Carbopol
Polyvinyl alcohol (PVA).
Polyvinyl pyrolidone (PVP)R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Finely Divided Solid
These agents form a particulate layer around dispersed
particles and swell in the dispersion medium to
increase viscosity and reduce the interaction between
dispersed droplets.
Most commonly they support the formation of o/w
emulsions,
✓Bentonite
✓Veegum,
✓Hectorite,
✓Magnesium Hydroxide,
✓Aluminum Hydroxide
✓Magnesium Tri silicate.
Erode-12

HLB for emulsifying agents
 The HLB number (1-20) represents the relative proportions
of the lipophilic and hydrophilic parts of the molecule.
 High numbers (8-18) indicate a hydrophilic molecule, and
produce an o/w emulsion.
 Low numbers (3-6) indicate a lipophilic molecule and
produce a w/o emulsion.
 Oils and waxy materials have a 'required HLB number'
which helps in the selection of appropriate emulsifying
agents when formulating emulsions.
 Liquid paraffin, for example, has a required HLB value
of 4 to obtain a w/o emulsion and 10.5 for an o/w emulsion.R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Chemical Designation HLB Value
Ethylene glycol distearate 1.5
Sorbitan sesquioleate 3.7
Diethylene glycol monostearate 4.7
Sucrose diolate 7.1
Polyoxyethylene (4) lauryl ether 9.5
Polyoxyethylene (6) cetyl ether 10.3
Polyxyethylene (20) sorbitan tristearate
Polyxyethelene (9) nonyl phenol
Sodium Oleate
Polyxyethylene (100) Stearate
Potassium Oleate
10.5
13.0
18.0
18.8
20.0R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Selection of emulsifying agent
An ideal emulsifying agent should be in
 It should be able to reduce the interfacial tension between the two
immiscible liquids. (Dp &Cp)
 It should be physically and chemically stable , inert and compatible
with the other ingredients of the formulation.
 It should be non irritant and non toxic.
 It should be organoleptically inert (color , odour or taste)to the
preparation.
 It should be able to produce and maintain the required viscosity of the
preparation. R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Preservation of Emulsion
Microbial contamination may occur due to:
 contamination during development or production of
emulsion or during its use.
 Usage of impure raw materials
 Poor sanitation conditions
 Invasion by an opportunistic microorganisms.
 Contamination by the consumer during use of the
product..
How to prevent microbial growth?
 Use of uncontaminated raw materials
 Careful cleaning of equipment with steam .R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

The ideal preservative should be in
 Acceptable taste, odor and color.
 Effective against fungus, yeast, bacteria.
 Available in oil and aqueous phase at effective level
concentration.
 Preservative should be in unionized state to penetrate the
bacteria.
 Preservative must no bind to other components of the
emulsion R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Stability of Emulsion
o An emulsion is said to be stable if it remains as such
after its preparation , that is the dispersed globules are
uniformly distributed through out the dispersion
medium during its storage.
o The emulsion should be chemically stable and there
should not be any bacterial growth during it shelf life.
Emulsion instability may either reversible
 Cracking (irreversible instability)
 Flocculation
 Creaming
 Phase inversion R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Flocculation
Phase inversion
Creaming Sedimentation Coalescence
Mechanisms of Emulsion Instability
o/w w/o
Breaking
Erode-12

Cracking
The separation of two layers of disperse and continuous
phase , due to the coalescence of disperse phase globules which
are difficult to redisperse by shaking.
Cracking may occurs due to following reasons:-
 By addition of emulsifying agent of opposite type
 By decomposition or precipitation of emulsifying agent
 By addition of common solvent
 By microorganisms
 Change in temperature
 By creaming
Erode-12

Flocculation
 In flocculated state the secondary interaction (van der
waals forces) maintain the droplets at a defined
distance of separation.
 Application of shearing stress to the formulation
(shaking) will redisperse these droplets to form a
homogeneous formulation.
 Although flocculation may stabilise the formulation,
there is also possibility that the close location of
droplets would enable droplet coalescence to occur if
the mechanical properties of the interfacial film are
compromised. R.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Creaming
 Creaming may be defined as the upward movement of dispersed
globules to form a thick layer at the surface of emulsion.
 Creaming is temporary phase because it can be re-distributed by mild
shaking or stirring to get again a homogenous emulsion.
 The factors affecting creaming are described by stoke’s law:
V= 2r 2 (d1 -d2 ) g/9 n
where
v = rate of creaming
r =radius of globules
d1= density of dispersed phase
d2= density of dispersion medium
g = gravitational constant
n = viscosity of the dispersion mediumR.Vijayakumar M Phram., Asst Professor,VCP
Erode-12

Phase inversion
Phase inversion means the change of one type of
emulsion into other type, that is oil in water emulsion
changes into water in oil type and vice-versa.
 By the addition of an electrolyte
 By changing the phase-volume ratio
 By temperature change
 By changing the emulsifying agent
o The phase inversion can be minimised by keeping
concentration of disperse phase between 30 to 60 % ,
o storing the emulsion in cool place and using a proper
emulsifying agent in adequate concentration.
Erode-12

A good emulsion considered with
o Stability of the active ingredient
o Stability of the excipients
o Visual appearance
o Color &Odor (development of pungent odor/loss of fragrance)
o Viscosity,
o Loss of water and other volatile vehicle components
o Concentration of emulsifier
o Particle size distribution of dispersed phases
o pH & Temperature
o Texture, feel upon application (stiffness, etc.,)
o Microbial contamination/sterility
o Release/bioavailability (percutaneous absorption)
Erode-12

PHYSICAL PHARMACEUTICS II COARSE DISPERSION

PHYSICAL PHARMACEUTICS II COARSE DISPERSION

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