Physical Pharmaceutics II –

BP403T
Dr. Asim Kumar Samanta
Assistant Professor
Dr. Vishwanath Karad MIT World Peace University,
School of Health Science and Technology,
Kothrud, Pune, Maharashtra 411038
Coarse Dispersion
Unit III

2
Syllabus
• Suspension, interfacial properties of suspended particles, settling in
suspensions, formulation of flocculated and deflocculated
suspensions.
• Emulsions and theories of emulsification, microemulsion and multiple
emulsions; Stability of emulsions, preservation of emulsions,
rheological properties of emulsions and emulsion formulation by HLB
method.

3
Particulate systems
• Particulate systems have been classified on the basis of size into --
• molecular dispersions
• colloidal systems
• coarse dispersions
• The theory and technology of these important pharmaceutical classes
are based on
• interfacial and colloidal principles
• micromeritics
• rheology

4
Suspension
• A pharmaceutical suspension is a coarse dispersion of insoluble solid
particles in a liquid medium.
• Particle diameter typically > 0.1 μm.
• Brownian movement observed under low viscosity.
• Desired Qualities of Suspensions
• Slow settling of suspended material.
• Easily re-dispersible particles.
• Optimal viscosity for pouring and injection.
• External lotions: easy spreading, quick drying, elastic film, acceptable color
and odor.
5
Suspension
• Importance of Dispersed Phase Characteristics
• Optimize physical, chemical, and pharmacologic properties.
• Consider particle-size distribution, specific surface area, inhibition of crystal
growth, polymorphic form.
• Ensuring Physical Stability
• Defined as particles not aggregating and remaining uniformly distributed.
• Settlement should allow easy resuspension with moderate agitation.
• Formulation Considerations
• Choose ingredients for ease of incorporation.
• Ensure properties remain stable during storage.
6
Interfacial Properties of Suspended Particles
• Thermodynamic Considerations
• Surface energy of solid particles makes the system thermodynamically
unstable.
• Particles tend to regroup to reduce total area and surface energy.
• Flocculation: Formation of light, fluffy conglomerates held by weak van der
Waals forces.
• Aggregation: Stronger forces lead to formation of solid aggregates (cake),
especially in compacted conditions.

7
Surface free energy
• Surface free energy
• Increase in work (W) or surface free energy (ΔG) due to increased surface
area (ΔA) and interfacial tension (γSL) between liquid medium and solid
particles.
∆𝐺 = 𝛾𝑆𝐿. Δ𝐴
• System tends to reduce surface free energy to reach equilibrium (ΔG = 0).
• Equilibrium can be achieved by reducing γSL or decreasing ΔA.
• Reduction of ΔA may lead to flocculation or aggregation, impacting
suspension stability.
• Addition of surfactant can reduce interfacial tension but rarely eliminates it

8
Interfacial Properties of Suspended Particles
• Interparticle Forces
• Forces of attraction (London–van der Waals) and
repulsion (electric double layers).
• Electric double-layer formation and zeta potential crucial
for understanding suspension stability.
• Energy Barrier and Particle Interaction
• Potential energy of particles plotted against
separation distance.
• High repulsion energy leads to a high energy barrier,
resisting particle collision.
• Deflocculated particles form close-packed arrangement
post-sedimentation, forming a hard cake.
• Flocculated particles remain at a distance, forming
loosely structural flocs.

9
Settling in Suspension
• Theory of Sedimentation: The velocity of sedimentation is expressed
by Stokes's law:

• Where: v: Terminal velocity (cm/sec), d: Diameter of particle (cm), ρs: Density

of dispersed phase, ρo: Density of dispersion medium, g: Acceleration due to
gravity, ηo: Viscosity of dispersion medium (poise)
• Modification of Stokes's Equation
• Accounting for nonuniform particle shape and size.
• Proposed modification: 𝑣 ′ = 𝑣𝜖 𝑛
• Where: v': Rate of fall at interface (cm/sec), ε: Initial porosity of the system
(varies from 0 to 1), n: Exponent representing system hindrance

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Settling in Suspension
• Dilute vs. Concentrated Suspensions
• Dilute suspensions (< 2 g solids per 100 mL) follow Stokes's law.
• Hindered settling observed in suspensions with higher particle
concentrations.
• Interference among particles disrupts free settling.

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Settling in Suspension
• Effect of Brownian Movement
• Brownian movement counteracts sedimentation to a measurable extent for
particles having a diameter of about 2 to 5 μm (depending on the density of
the particles and the density and viscosity of the suspending medium), at
room temperature by keeping the dispersed material in random motion.
• Ordinary pharmaceutical suspensions with suspending agents unlikely to
exhibit vigorous Brownian motion.

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Sedimentation of Flocculated Particles
• Sedimentation in flocculated systems leads to distinct boundaries
between sediment and supernatant liquid → Clear supernatant
indicates flocculated system.
• Contrast with deflocculated suspensions where larger particles settle
more rapidly than smaller ones, leading to turbidity → Turbid
supernatant suggests deflocculated suspension.

13
14
 Sedimentation Parameters
• Sedimentation Volume (F):
• Ratio of final sediment volume (Vu) to
original suspension volume (Vo).
𝑉𝑢
𝐹 = ൗ𝑉
𝑜
• F can be less than 1 (indicating smaller
sediment volume), equal to 1
(flocculation equilibrium), or greater
than 1 (expanded floc network).

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Sedimentation Parameters
• For deflocculated suspension, the final volume of the sediment (V∞) will
be relatively small compared to original suspension volume (Vo).
𝑉∞
𝐹∞ = ൗ𝑉
𝑜
• Degree of Flocculation (β):
• Definition: Ratio of F to sedimentation volume of deflocculated suspension (F∞).
𝑉𝑢
ൗ𝑉
𝑉
𝛽 = 𝐹ൗ𝐹 = 𝑜
= 𝑢ൗ𝑉
∞ 𝑉∞ ∞
ൗ𝑉
𝑜
• Degree of Flocculation (β) is more fundamental parameter than sedimentation
volume (F), because it relates the volume of flocculated sediment to that in a
deflocculated system
𝐹𝑖𝑛𝑎𝑙 𝑠𝑒𝑑𝑖𝑚𝑒𝑛𝑡𝑎𝑡𝑖𝑜𝑛 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝒇𝒍𝒐𝒄𝒄𝒖𝒍𝒂𝒕𝒆𝒅 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛
• Thus, 𝛽 =
𝐹𝑖𝑛𝑎𝑙 𝑠𝑒𝑑𝑖𝑚𝑒𝑛𝑡𝑎𝑡𝑖𝑜𝑛 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝒅𝒆𝒇𝒍𝒐𝒄𝒄𝒖𝒍𝒂𝒕𝒆𝒅 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛
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Formulation of Suspensions
• Wetting of Particles
• Controlled Flocculation
• Flocculation in Structured Vehicle
• Rheologic Considerations

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Formulation of Suspensions
• Two main approaches for preparing physically stable suspensions:
• a. Use of structured vehicles to maintain deflocculated particles.
• b. Application of flocculation principles to produce settleable flocs easily
resuspended.
• Structured Vehicles
• Pseudoplastic and plastic in nature.
• Rheologic properties.
• Ideally, structured vehicles prevent settling by entrapping particles, though
some sedimentation may occur.
• "Shear-thinning" property aids in uniform dispersion reformation upon
agitation.
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1. Wetting of Particles
• Wetting of Particles
• Initial dispersion of insoluble powder crucial in manufacturing processes.
• Powders often difficult to disperse due to adsorbed air, grease, and contaminants.
• Wettability Assessment
• Contact angle measurement on liquid surface indicates wettability.
• High contact angle (~90°) indicates poor wetting, with particles floating on liquid.
• Low contact angle or absence indicates good wetting or sinking of particles.

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1. Wetting of Particles
• Hydrophobic vs. Hydrophilic Powders
• Hydrophobic powders (e.g., sulfur, charcoal, magnesium stearate) show large contact
angles and resist water wetting.
• Hydrophilic powders (e.g., zinc oxide, talc) readily wet when free of contaminants.
• Role of Surfactants
• Surfactants reduce interfacial tension between solid particles and vehicle.
• Lowering interfacial tension promotes wetting and deflocculation.
• Use of Hygroscopic Substances
• Glycerin aids in levigating insoluble material by displacing air and promoting wetting.
• Allows water penetration into particle interstices, aiding dispersion.

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 2. Controlled Flocculation
• Controlled Flocculation
• Controlled flocculation is essential to prevent the formation of compact sediments in
suspensions, ensuring ease of redispersement.
• This process involves the use of electrolytes, surfactants, and polymers to manipulate particle
interactions and structure.
• 1. Electrolytes as Flocculating Agents:
• Electrolytes reduce electric barrier between particles, leading to a decrease in zeta potential.
• Formation of bridges between adjacent particles facilitates loose arrangement into flocs.
• 2. Polymers in Flocculation:
• Polymers are long-chain, high–molecular-weight compounds containing active groups spaced
along their length.
• Part of the chain is adsorbed on the particle surface → remaining parts projecting out into the
dispersion medium → Bridging between these latter portions leads to the formation of flocs →
Flocculating agent
• Hydrophilic polymers also act as protective colloids and particles coated in this manner are less
prone to cake than are uncoated particles.
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Caking diagram, showing the
flocculation of a bismuth
subnitrate suspension by means
of the flocculating agent
monobasic potassium phosphate.

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2. Controlled Flocculation
• 3. Surfactants in Flocculation:
• Surfactants, both ionic and nonionic, can induce flocculation by altering
particle interactions.
• Concentration of surfactants must be carefully controlled to avoid
deflocculation.
• 4. pH Adjustment for Desired Surface Charge:
• pH adjustment influences surface charge of particles, affecting their
interaction in suspension.
• Zero point of charge is crucial; achieved through addition of acids or bases.

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3. Flocculation in Structured Vehicles
• Flocculation in Structured Vehicles
• Controlled flocculation ensures desired physical and chemical characteristics
of pharmaceutical suspensions
• However, product can look unsightly if sedimentation volume (F) is not close
to or equal to 1.
• Therefore, addition of suspending agents like carboxymethylcellulose,
Carbopol 934, Veegum, tragacanth, and bentonite commonly used to retard
sedimentation of flocs.
• Used alone or in combination to enhance suspension stability.

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3. Flocculation in Structured Vehicles
• Consideration of Compatibility
• Incompatibilities arise based on particle charge and
charge carried by flocculating and suspending agents.
• Example: Addition of anionic flocculating agent to
positively charged particles is compatible with
negatively charged suspending agents, but may lead
to incompatibility with cationic electrolytes.
• Role of Protective Colloids
• To overcome incompatibilities, use of protective
colloids to change particle charge.
• Adsorption of fatty acid amines or positively charged
materials like gelatin onto particle surface.
• Enables use of anionic electrolytes to produce
compatible flocs with negatively charged suspending
agents.
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4. Rheologic Considerations
• Ideal Suspending Agent Characteristics
• High viscosity at negligible shear (during storage).
• Low viscosity at high shear rates (during agitation,
pouring, spreading).
• Desirable properties shown by pseudoplastic
substances like tragacanth, sodium alginate, and
sodium carboxymethylcellulose.
• Comparison with Newtonian Liquids
• Newtonian liquid glycerin has suitable viscosity for
suspending particles but is too high to pour easily and
spread on skin.
• Glycerin also exhibits undesirable properties like
tackiness and high hygroscopicity.

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4. Rheologic Considerations
• Thixotropic Properties
• Thixotropic suspending agents form a
gel on standing and become fluid
when disturbed.
• Example: Bentonite, Veegum, and their
combination with sodium
carboxymethylcellulose exhibit
pseudoplastic and thixotropic
characteristics.

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Preparation of Suspensions
• Small Scale Preparation
• Insoluble material ground or levigated in mortar with vehicle containing
dispersion stabilizer.
• Gradually adding remaining liquid phase, including soluble drugs, to achieve
smooth paste.
• Transfer to graduate, rinse mortar with vehicle, bring dispersion to final
volume.

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Preparation of Suspensions
• Large Scale Preparation
• Dispersion accomplished using ball, pebble, and colloid
mills, as well as dough mixers and similar apparatus.
• Focus on colloid mill: high-velocity, cone-shaped rotor
centered with respect to stator at adjustable clearance.
• Operation of Colloid Mill
• Suspension fed to rotor by gravity, sheared between
rotor and stator, forced out below stator for recycling
or withdrawal.
• Efficiency based on clearance between disks, rotor
peripheral velocity, and non-Newtonian viscosity of
suspension.
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Emulsions
• Definition of Emulsions
• Thermodynamically unstable system comprising at least two immiscible liquid
phases.
• One phase dispersed as globules (dispersed phase) in the other liquid phase
(continuous phase).
• Stabilized by emulsifying agent.
• Emulsion Types
• Oil-in-water (o/w) emulsion: Oil phase dispersed in aqueous continuous
phase.
• Water-in-oil (w/o) emulsion: Water phase dispersed in oil continuous phase.
• Medicinal emulsions for oral administration mostly o/w type; external
emulsions can be o/w or w/o.
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Identification test for emulsion type
• Following tests are done to distinguish between
o/w and w/o emulsion
• Dilution test
• Dye test
• Conductivity test
• Dilution test: Based on the solubility of
external phase of emulsion
• o/w emulsion remains stable after dilution with
water and break after dilution with oil.
• w/o emulsion remains stable after dilution with oil
and break after dilution with water.

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Identification test for emulsion type
• Dye solubility test:
• when an emulsion is mixed with a water soluble dye such as amaranth and
observed under the microscope.
• if the continuous phase appears red under microscope, then it means that the
emulsion is o/w type as water is the external phase
• if the scattered globules appear red and continuous phase colorless under
microscope, then it is w/o type.
• Opposite phenomenon will be seen for oil soluble scarlet red dye.

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Identification test for emulsion type
• Conductivity Test:
• Based on the principle that water is good conductor of electricity whereas oil is non-
conductor.
• The conductivity test can be performed by dipping a pair of electrode connected
through a low voltage bulb in the emulsion
• If the bulb glows on → emulsion is o/w type
• If the bulb does not glow → emulsion is w/o type

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Pharmaceutical Applications of Emulsions
• 1. Oral Administration of Water-Insoluble Liquids:
• Oil-in-water (o/w) emulsions are ideal for orally administering water-insoluble liquids.
• Particularly useful when the dispersed phase has an unpleasant taste, enhancing patient
compliance.
• 2. Enhanced Absorption of Oil-Soluble Compounds:
• Some oil-soluble compounds, like certain vitamins, are absorbed more efficiently when
emulsified.
• Emulsions improve bioavailability compared to oily solutions when administered orally.
• 3. Intravenous Administration and Drug Delivery:
• Intravenous emulsions offer an alternative method for delivering drugs to debilitated
patients.
• 4. Influence of Droplet Size and Emulsifying Agents:
• Droplet size and emulsifying agents affect phagocytosis of lipid emulsions.
• Clearance rate by macrophages increases with larger droplet size or surface charge,
impacting drug delivery kinetics → emulsion droplets stabilized by a nonionic surfactant (zero
surface charge) were cleared much more slowly than the droplets stabilized by negatively
charged phospholipids
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Pharmaceutical Applications of Emulsions
• 5. Radiopaque Emulsions for Diagnostic Imaging:
• Emulsions serve as diagnostic agents in x-ray examinations, offering radiopacity for
enhanced imaging.
• 6. Pharmaceutical and Cosmetic Products:
• Emulsification is widely used in pharmaceutical and cosmetic products for external
use.
• Dermatologic and cosmetic lotions and creams benefit from easy spreadability and
non-greasiness, enhancing patient acceptance.
• 7. Aerosol Products and Foam Formation:
• Emulsification in aerosol products generates foams upon discharge.
• Propellant vaporization creates rapid foam formation, suitable for various
applications.

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Theories of Emulsification
• Cohesive and Adhesive Forces:
• Immiscible liquids separate due to cohesive forces within each liquid being greater
than adhesive forces between them.
• Failure of mixing explained by the dominance of cohesive forces over adhesive
forces.
• Interfacial Area and Surface Free Energy:
• Breaking one liquid into small particles increases interfacial area exponentially.
• Enormous surface area leads to thermodynamic instability, promoting droplet
coalescence.
• Theories of Emulsion Stability: Various theories explain emulsion stability
and the role of emulsifying agents:
• a. Monomolecular film theory
• b. Multimolecular film theory
• c. Particulate film theory
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Theory of emulsification
• Surfactant (Monomolecular adsorption): To
reduce the interfacial tension Oil droplets are
surrounded by a coherent monolayer of the
surfactant which prevents coalescence. If the
emulsifier is ionized, the presence of strong
charge may lead to repulsion in droplets and
hence increasing stability.
• Hydrophilic Colloids (Multimolecular
adsorption)
• Finely divided solid particles (solid particles
adsorption): They are adsorbed at the interface
between two immiscible liquid phases to form
Particulate film.

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Monomolecular adsorption
• Amphiphiles (surfactants) reduce interfacial tension (to 1 dyne/cm)
because of adsorption at interface o/w
• Droplets are surrounded by coherent monolayer that help prevent
coalesence (merging) between two droplets.
• Surface Charge cause repulsion between globules.
• Combination of surfactants is generally used as it is more effective.
• Combination of Sodium cetyl sulphate and cholesterol leads to complex film
that produce excellent emulsion.
• Hydrophilic tween can be combined with lipophilic span, in varying
proportions to produce satisfactory emulsion.
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Three mixtures of emulsifying agents at the
oil–water interface
Combination of sodium cetyl sulfate and cholesterol leads to a
complex film → produces an excellent emulsion.

Sodium cetyl sulfate and oleyl alcohol do not form a

closely packed film → Results in a poor emulsion.

Cetyl alcohol and sodium oleate produce a close-packed film,

but negligible complexation → Results in a poor emulsion.

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Tween and Span
• Molecular structure of surfactants
a) Span 80 (Sorbitan monooleate) – Lipophilic
b) Tween 80 (Polyoxyethylene sorbitan monooleate) – Hydrophilic

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Combination of Tween and Span
• Combination of Tween and Span:
• Varying proportions create desired o/w or w/o emulsion.
• Molecular Arrangement:
• Span 80's hydrocarbon portion in oil globule, sorbitan
radical in aqueous phase.
• Bulky sorbitan heads prevent close association of
hydrocarbon tails in oil phase.
• Addition of Tween 40 reorients at interface, with
hydrocarbon tail in oil phase and remainder in water
phase.
• Interfacial Film Strengthening:
• Tween 40's hydrocarbon chain between Span 80 chains
enhances van der Waals attraction.
• Strengthened interfacial film increases stability of o/w
emulsion against particle coalescence.

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Emulsion Type and Hydrophile-Lipophile
Balance (HLB)
• Dependence on Emulsifying Agent Property
• Emulsion type (o/w or w/o) primarily determined by emulsifying agent's properties.
• HLB signifies polar-nonpolar nature of the emulsifier.
• Prediction of Surfactant Roles
• Knowledge of HLB predicts surfactant's role: emulsifier, wetting agent, detergent, or
solubilizing agent.
• Effect of HLB on Emulsion
• Emulsifying agents have lipophilic (oil-loving) and hydrophilic (water-loving)
components→ Balance of these properties determines emulsion type.
• Higher HLB (e.g., blend of Tween 20 and Span 20) favors o/w emulsion.
• Lower HLB (e.g., Span 60) tends to form w/o emulsion.
• Generally, o/w emulsions occur at HLB 9-12, w/o emulsions at HLB 3-6.

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Bancroft's Rule
• Bancroft's Rule
• Emulsion type depends on surfactant solubility: more soluble phase becomes
the continuous phase.
• Higher HLB agents preferentially soluble in water, leading to o/w emulsions.

43
Emulsifying agents – HLB
HLB Application
value
1-3 Anti-foaming agent.
3-6
W/O emulsifying agents.
7-9 Wetting agents.
✓ The system is called the HLB (hydrophile-
8 - 18
O/W emulsifying agents. lipophile balance) system and has an arbitrary
scale of 1 - 20.
13 -15 Detergents
✓ HLB numbers are experimentally determined
15 -18 Solubilizing Agents for the different emulsifiers.

Saponification number represents the number of milligrams of KOH or NaOH required to saponify one
gram of fat. It is a measure of the average molecular weight (or chain length) of all the fatty acids.
Acid number the quantity of milligrams of KOH required to neutralize the acidic constituents in 1
gram of a sample. it is a measure of free fatty acids (FFAs) present in a substance 44
Multimolecular Adsorption
• Hydrophilic colloids (mucilage of gum acacia) are different in action
from surfactants.
• They do not cause lowering of interfacial tension.
• They form multimolecular layer at o/w interface
• They increase viscosity of dispersion medium

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Emulsifying agents – Hydrocolloids
• Natural Polysaccharides: The main problem with these agents is their
natural variability between batches and microbial contamination.
• These materials should not be used externally as they leave a sticky feel on
the skin.
• Acacia is the best emulsifying agent for extemporaneously prepared oral
emulsions as it forms a thick film at the oil- water interface to act as a
barrier to coalescence. It is too sticky for external use.
• Tragacanth is used to increase the viscosity of an emulsion and prevent
creaming.
• Other polysaccharides, such as starch, pectin and carrageenan, are used to
stabilize an emulsion.
46
Emulsifying agents – Hydrocolloids
• Semi-synthetic polysaccharides: These are derived from the naturally
occurring polysaccharide cellulose and generally form o/w emulsions.
• Examples include low-viscosity grades of
• Methylcellulose (MC)
• Carboxymethylcellulose (CMC)
• Hydroxypropylmethylcellulose (HPMC)
• Synthetic hydrocolloids:
• Carbopol
• Polyvinyl alcohol (PVA).
• Polyvinyl pyrolidone (PVP)

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Solid-Particle Adsorption
• Solid particles that can be wetted by oil as well as water can act as
emulsifying agent
• Their concentration is higher at interface
• They form particulate film around dispersed droplets to prevent
coalescence
• Example of agents: Bentonite (Al2O3 .4SiO2 .H2O), Veegum
(Magnesium Aluminum Silicate)

48
Emulsifying agents – Finely dispersed solids
• These agents form a particulate layer around dispersed particles.
• These agents 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.
49
Physical Stability of Emulsions
• Classification of Instability
• Flocculation and creaming.
• Coalescence and breaking.
• Phase inversion.

50
Creaming and Stokes's Law
• Creaming in emulsions governed by Stokes's law.

• Direction of Creaming
• Dispersed phase less dense than continuous phase leads to upward creaming
(o/w emulsions).
• Heavier internal phase settles downward (w/o emulsions)→ creaming in a
downward direction
• Creaming increased by -
• Greater the difference between the density of the two phases
• Larger the oil globules
• Less viscous the external phase
51
Creaming and Stokes's Law
• Controlling Creaming
• Increasing viscosity of external phase by viscosity improvers or thickening
agents such as methylcellulose, tragacanth, or sodium alginate.
• Reducing globule size through homogenization crucial for stability→
Brownian motion slows creaming for particles below 2 to 5 μm diameter.
• Adjusting densities of phases theoretically eliminates creaming tendency →
Challenges due to temperature changes altering densities.
• Addition of oil-soluble substances used to increase oil phase density.
• Example: α-bromonaphthalene, bromoform, carbon tetrachloride (limited use in
medicinal products).

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Coalescence and Breaking
• Distinguishing Creaming from Breaking
• Creaming is reversible, breaking is irreversible.
• Creamed emulsions easily redispersed, while broken emulsions resist reconstitution.
• Impact of Film Destruction
• Breaking results from destruction of emulsifier film surrounding oil globules.
• Prevents resuspension of globules, leading to coalescence.
• Factors Influencing Breaking
• Optimal dispersion level crucial for stability→ Reduction of particle size doesn't
always enhance stability.
• Viscosity and phase-volume ratio influence stability.
• Electrostatic Stabilization
53
Coalescence and Breaking
• Viscosity
• Viscosity alone does not produce stable emulsions → Viscosity plays only a minor
role in the gross stability of o/w emulsions
• Probably an optimum rather than a high viscosity is needed to promote stability
• Optimal Dispersion
• Moderate dispersion of uniform-sized particles promotes stability.
• Nonuniform dispersion allows small particles to wedge between larger ones,
promoting coalescence.
• Phase-Volume Ratio
• Exceeding critical point (about 74% oil) leads to coalescence and breaking.
• Critical point is defined as the concentration of the internal phase above which the
emulsifying agent cannot produce a stable emulsion of the desired type.
• Optimal stability achieved with 50:50 phase-volume ratio.

54
Coalescence and Breaking
• Electrostatic Stabilization
• Zeta potential influences stability by electrostatic repulsion between droplets.
• Lecithin stabilizes emulsions through electrostatic repulsion, forming negative charge
at droplet surface.
• Effect of Electrolytes
• Addition of electrolytes or cationic species may reduce zeta potential, leading to
flocculation.
• Divalent electrolytes like calcium cause charge reversal and flocculation in presence
of heparin.
• Role of Emulsifier Film
• Emulsifier film at interface crucial for stabilization.
• Must be tough, elastic, and rapidly forming during emulsification.

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Phase Inversion
• Phase inversion means change in the type of emulsion i.e. o/w to w/o
or vice versa
• Reasons for phase inversion.
• Addition of electrolyte: Addition of calcium chloride to o/w emulsion
stabilizes with sodium stearate, forming calcium stearate and resulting in w/o
emulsion.
• Changing phase volume ratio.
• Temperature change.
• Changing the emulsifying agent.

56
Preservation of Emulsions
• Microbial Contamination:
• Undesirable changes caused by microorganism growth.
• Physical separation, discoloration, gas/odor formation, and rheological changes.
• Emulsions for parenteral use must be sterile.
• Microbial Propagation:
• Microorganisms degrade emulsifying agents, thickeners, etc.
• Formulate emulsions with adequate preservatives to resist microbial attack.
• Preservative Considerations:
• Ensure preservative concentration matches contamination type.
• Factors influencing preservative effectiveness: partitioning, ionization, and binding.

57
Preservation of Emulsions
• Ideal Preservative Characteristics:
• Partitioning between oil and water phases affects preservative efficacy (bacteria
grow in the aqueous phase → preservative partitioned strongly in favor of the oil
phase may be virtually useless)
• Ionization: pH affects activity of weak acid preservatives (activity of weak acid
preservatives decreases as the pH of the aqueous phase rises)→ preservative must
be in an un-ionized state to penetrate the bacterial membrane
• Binding: Presence of unbound preservative molecules essential for effectiveness
(preservative bound to other components (complexes) are ineffective.
• Additional Factors:
• Influence of emulsion type, product nutritive value, degree of aeration, and
container type on preservative efficacy.
58
Rheologic Properties of Emulsions
• Shear Stress and Flow Properties:
• Emulsified products subjected to various shear stresses during preparation or use.
• Proper flow properties vital for performance in different conditions
• Flow of a parenteral emulsion through a hypodermic needle
• Removal of an emulsion from a bottle or a tube
• Behavior of an emulsion in the various milling operations employed in the large-scale manufacture
• Controlled Spreadability:
• Spreadability crucial for dermatologic and cosmetic products.
• Flow behavior important in parenteral emulsion administration and large-scale
manufacturing.
• Flow Properties:
• Most emulsions exhibit non-Newtonian flow except dilute ones.
• Phase-volume ratio and particle-size distribution affect flow.
• Viscosity of continuous phase and internal phase viscosity affects flow properties.

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Multiple emulsions
• Oil-in-Water-in-Oil:
• In O/W/O systems an aqueous phase (hydrophilic) separates internal and
external oil phase. In other words, O/W/O is a system in which water droplets
may be surrounded in oil phase, which in true encloses one or more oil
droplets.
• Water-in-Oil-In-Water:
• In W/O/W systems, an organic phase (hydrophobic) separates internal and
external aqueous phases. In other words, W/O/W is a system in which oil
droplets may be surrounded by an aqueous ; phase, which in turn encloses
one or several water droplets. These systems are the most studied among the
multiple emulsions.

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Microemulsion
• Clear, stable, liquid mixtures of oil, water and surfactant, frequently in
combination with a co-surfactant.
• In contrast to ordinary emulsion, Microemulsions form upon simple
mixing of the components and do not require the high shear
conditions generally used in the formation of ordinary emulsions.
• The two basic types of Microemulsions are (o/w) and (w/o).
• Unlike the common macro emulsion in that:
• Appear as clear transparent solution
• Diameter of internal phase droplets ranged between 10-200nm.
• Thermodynamically stable
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Identification test for emulsion type
• Fluorescence test
• Certain vegetable oils fluoresce in UV light
• Emulsion exposed to UV light and observed microscopically
• If whole field fluoresces indicates oil present in continuous phase → w/o type emulsion
• If droplet fluoresce indicates oil present in disperse phase → o/w type emulsion

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