Emulsions

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Emulsions
Emulsion suitable for intravenous injection.
Sodas Oil in Water emulsion
Balm Water in oil emulsion
Milk Oil in Water emulsion
Mayonnaise Oil in Water emulsion
Dodecane droplets in a continuous phase of
water/glycerol mixture.
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• Emulsion Dispersion of liquid droplets
  (dispersed phase) of certain size within a second
  immiscible liquid (continuous phase).
• Classification of emulsions
• - Based on dispersed phase
• Oil in Water (O/W) Oil droplets dispersed in
  water
• Water in Oil (W/O) Water droplets dispersed
  in oil
• Water in Oil in water (W/O/W) Water in Oil
  emulsion dispersed in water multiple emulsion
• - Based on size of liquid droplets
• 0.2 50 mm Macroemulsions
• 0.01 0.2 mm Microemulsions

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Advantages

• Administration of Distasteful oil, mask the
  unpleasant taste
• Better and faster absorption
• Less irritation to the skin
• Sustained release medication
• Nutritional supplement
• Diagnostic purposes

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Emulsions encountered in everyday life!
Stability of emulsions may be engineered to vary
from seconds to years depending on application
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Emulsifying Agents

• Stable dispersions of liquids constituting the
  dispersed phase, in an immiscible liquid
  constituting the continuous phase is brought
  about using emulsifying agents such as
• Carbohydrates acacia, tragacanth, agar, chondrus
  and pectin
• Proteins gelatin, egg yolk and casein
• High mol wt alcohols stearyl alcohol, cetyl
  alcohol,
• glycery monostearate, cholesterol
  w/o stabilisers
• Surfactants SPAN, TWEEN, organic soaps
• ( triethanolamine oleate),
• Non ionic- pH 3-10, cationic 3-7, anionic-
  greater than 8

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Common Emulsifying Agents

• Surfactants
• Anionic Sodium stearate, Potassium laurate
• Sodium dodecyl sulfate, Sodium sulfosuccinate
• Nonionic Polyglycol, Fatty acid esters,
  Lecithin
• Cationic Quaternary ammonium salts,
• Finely divided Solids
• Finely divided solids with amphiphilic properties
  such as
• silica and clay, may also act as emulsifying
  agents
• Others bentonite, magnesium hydroxide, Al(OH)3

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Tests for Emulsion Type (W/O or O/W emulsions)

• Based on the Bancrofts rule, many emulsion
  properties are
• governed by the properties of the continuous
  phase
• Dye test
• Dilution test
• Electrical conductivity measurements
• 4. Filter paper test

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Thermodynamic instability

• ? G ? . ? A
• Increase in the surface free energy interfacial
  tension X increased surface area

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Mechanism of emulsification

• Monomolecular theory
• Surfactants
• Reduce interfacial tension
• Forms a protective film around globule
• Ionic surfactant exert repulsion between globules

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Mechanism

• Multimolecular theory
• Hydrocolloids form multimolecular physical
  barrier around globules there by prevent
  coalescence of oil globules
• Acacia, gelatin
• Solid particle adsorption theory

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Physical Instability

• Creaming Concentration of globules at the top or
  bottom of emulsion.
• Reversible process but leads to breaking
• Influenced by Stokes equation
• V h d2st (?s?o) g
• t 18?o
• -globule size
• -Viscosity of dispersion medium
• -Difference in the densities of dispersed and
  dispersion medium

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Creaming of Emulsions

• Droplets larger than 1 mm may settle
  preferentially to the top or the bottom under
  gravitational forces.
• Creaming is an instability but not as serious as
  coalescence or breaking of emulsion
• Probability of creaming can be reduced if
• a - droplet radius, ?? - density difference,
• g - gravitational constant, H - height of the
  vessel,
• Creaming can be prevented by homogenization. Also
  by reducing ??, creaming may be prevented.

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Creaming can be reduced/prevented by

• Reducing the globule size by homogenization
• Increasing the viscosity of dispersion medium
• Reducing the difference in densities

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Coalescence

• Separation of two phases due to fusion of
  globules. Also called cracking of emulsion.
• Irreversible process.
• Sheath of EA around globules is lost.
• Creaming leads to breaking- globules comes nearer
• Breaking of emulsion is observed due to
• Insufficient amount of EA
• Incompatibility between EA
• Alteration in the properties of EA

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Inversion of Emulsions (Phase inversion)

• O/W? W/O
• The order of addition of the phases
• W ?O emulsifier ? W/O
• O ?W emulsifier ? O/W
• Nature of emulsifier
• Making the emulsifier more oil soluble tends to
  produce a W/O emulsion and vice versa.
• Phase volume ratio
• Oil/Water ratio? ?W/O emulsion and vice versa

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Inversion of Emulsions (Phase inversion)

• 4. Temperature of the system
• ?Temperature of O/W (polyoxyethylenated nonionic
  surfactant) makes the emulsifier more hydrophobic
  and the emulsion may invert to W/O.
• 5. Addition of electrolytes and other
  additives.
• Strong electrolytes to O/W (stabilized by ionic
  surfactants) may invert to W/O
• Example. Inversion of O/W emulsion (stabilized
  by sodium cetyl sulfate and cholesterol) to a W/O
  type upon addition of polyvalent Ca.

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W/O vs. O/W emulsions

• Bancroft's rule
• Emulsion type depends more on the nature of the
  emulsifying agent than on the relative
  proportions of oil or water present or the
  methodology of preparing emulsion.
• The phase in which an emulsifier is more
  soluble constitutes the continuous phase
• In O/W emulsions emulsifying agents are
  more soluble in water than in oil (High HLB
  surfactants).
• In W/O emulsions emulsifying agents are
  more soluble in oil than in water (Low HLB
  surfactants).

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Emulsions

• Rate of coalescence measure of emulsion
  stability.
• It depends on
• Physical nature of the interfacial surfactant
  film
• For Mechanical stability, surfactant films are
  characterized
• by strong lateral intermolecular forces and high
  elasticity
• Mixed surfactant system preferred over single
  surfactant.
• (Lauryl alcohol Sodium lauryl sulfate
  hydrophobic interactions)
• combination of SPAN and TWEEN

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Emulsions

• (b) Electrical or steric barrier
• Significant only in O/W emulsions.
• In case of non-ionic emulsifying agents, charge
  may arise due to
• (i) adsorption of ions from the aqueous phase or
• (ii) contact charging (phase with higher
  dielectric constant is charged positively)
• No correlation between droplet charge and
  emulsion stability in W/O emulsions
• Steric barrier dehydration and change in
  hydrocarbon chain conformation.

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Emulsions

• (c) Viscosity of the continuous phase
• Higher viscosity reduces the diffusion
  coefficient
• Stoke-Einsteins Equation
• This results in reduced frequency of collision
  and therefore
• lower coalescence. Viscosity may be increased by
  adding
• natural or synthetic thickening agents.
• Further, ? ? as the no. of droplets?
• (many emulsion are more stable in concentrated
  form than when diluted.)

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Emulsions

• (d) Size distribution of droplets
• Emulsion with a fairly uniform size
  distribution is more stable than with the same
  average droplet size but having a wider size
  distribution
• (e) Phase volume ratio
• As volume of dispersed phase ? stability of
  emulsion ?
• (eventually phase inversion can occur)
• (f) Temperature
• Temperature ?, usually emulsion stability ?
• Temp affects Interfacial tension, D,
  solubility of surfactant, Brownian motion,
  viscosity of liquid, phases of interfacial film.

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Preparation of emulsion

• Dry gum method
• Wet gum method
• Bottle method

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Selection of Emulsifiers

• Correlation between chemical structure of
  surfactants and
• their emulsifying power is complicated because
• (i) Both phases oil and water are of variable
  compositions.
• (ii) Surfactant conc. determines emulsifier
  power as well as the type of emulsion.
• Basic requirements
• Good surface activity
• Ability to form a condensed interfacial film
• Appropriate diffusion rate (to interface)

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General Guidelines

1. Type of emulsion determined by the phase in which
   emulsifier is placed.
2. Emulsifying agents that are preferentially oil
   soluble form W/O emulsions and vice versa.
3. More polar the oil phase, the more hydrophilic
   the emulsifier should be. More non-polar the oil
   phase more lipophilic the emulsifier should be.

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General Guidelines

• HLB method HLB indicative of emulsification
  behavior.
• HLB 3-6 for W/O
• 8-18 for O/W
• HLB no. of a surfactant depend on which phase of
  the final emulsion it will become.
• Limitation does not take into account the
  effect of temperature.

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General Guidelines

• 2. PIT method At phase inversion temperature,
  the hydrophilic and lipophilic tendencies are
  balanced.
• Phase inversion temperature of an emulsion is
  determined using equal amounts of oil and aqueous
  phase 3-5 surfactant.
• For O/W emulsion, emulsifier should yield PIT of
  20-600C higher than the storage temperature.
• For W/O emulsion, PIT of 10-400C lower than the
  storage temperature is desired.

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General Guidelines

• Cohesive energy ratio (CER) method
• Involves matching HLBs of oil and emulsifying
  agents also molecular volumes, shapes and
  chemical nature.
• Limitation necessary information is available
  only for a limited no. of compounds.