Emulsions

• Emulsion


  A two-phase system prepared by combining two immiscible liquids, one of which is uniformly dispersed throughout the other in the form of small droplets (0.1-100 μm)
• Components of an emulsion

  • Dispersion medium (dispersed, internal, or discontinuous phase)
  • Dispersed medium (external phase or continuous phase)
• Oil-in-water (o/w) emulsion


  Oil is the dispersed phase and an aqueous solution is the continuous phase
• Water-in-oil (w/o) emulsion


  Water or an aqueous solution is the dispersed phase and oil or oleaginous material is the continuous phase
• Types of emulsions


  • Oil-in-water (o/w)
  • Water-in-oil (w/o)
  • Multiple emulsions (w/o/w or o/w/o)
• Micro-emulsion


  Emulsion with dispersed globules of colloidal dimensions (1 nm to 1 μm), often transparent or translucent
• Identifying emulsion type


  1. Miscibility tests with oil or water

  2. Conductivity measurements

  3. Staining tests
• Factors in choosing emulsion type


  • Route of administration
  • Medicament
• Factors in choosing oil phase


  • Active agent
  • Calorific value (for IV feeding)
  • Texture/feel (for external use)
  • Film forming properties
• Controlling emulsion rheology


  • Viscosity of dispersed phase
  • Particle size of dispersed phase
  • Viscosity of continuous phase
  • Viscosity of dispersed phase
  • Nature and concentration of emulsifying system
• Types of emulsifying agents


  • Synthetic or semi-synthetic surface-active agents
  • Naturally occurring agents and their derivatives
  • Finely divided solids
• Categories of synthetic/semi-synthetic surfactants


  • Anionic
  • Cationic
  • Non-ionic
  • Amphoteric
• Disadvantages of naturally occurring emulsifying agents


  • Batch to batch variation
  • Susceptibility to bacterial growth
• Finely divided solids used as emulsifying agents


  • Montmorillonite clays (bentonite, aluminum-magnesium silicate)
  • Colloidal silicon dioxide
  • Aluminum hydroxide
  • Magnesium hydroxide
• HLB (Hydrophile-Lipophile Balance) method


  Used to calculate relative quantities of emulsifiers to produce most physically stable emulsion for a particular oil-water combination
• Using the HLB method

  1. Determine total required HLB number

  2. Calculate quantity of each surfactant required in a surfactant blend
• Most stable emulsions are formed when all emulsifying agents are of the same hydrocarbon length
• Phase inversion temperature


  Temperature at which a non-ionic surfactant-stabilized o/w emulsion inverts to form a w/o product as the surfactant becomes more hydrophobic
• Other formulation additives


  • Antioxidants
  • Preservatives
  • Viscosity modifiers
  • pH adjusters
• HLB


  Hydrophilic-Lipophilic Balance
• Formulation of emulsions


  1. Produce a series of emulsions of varying HLB values

  2. Increase total emulgent concentration

  3. Use a different combination of emulsifying agents
• Phase inversion temperature


  1. As temperature increases, HLB value of a non-ionic surfactant decreases as it becomes more hydrophobic

  2. At the phase inversion temperature, the emulgent has equal hydrophilic and hydrophobic tendencies and the emulsion will invert
• Formulation additives


  • Antioxidants
  • Humectants
  • Preservatives
• Desirable features of a preservative


  • Wide spectrum of activity
  • Bactericidal rather than bacteristatic activity
  • Freedom from toxic, irritant or sensitizing activity
  • High water solubility
  • Compatibility with other ingredients and container
  • Stability and effectiveness over a wide range of pH and temperatures
  • Freedom from colour and odour
  • Retention of activity in the presence of large numbers of microorganisms
• Creaming


  Separation of an emulsion into two regions, one richer in the dispersed phase than the other
• Reducing creaming rate


  1. Produce an emulsion of small droplet size

  2. Increase viscosity of continuous phase

  3. Reduce density differences between phases

  4. Control disperse phase concentration
• Flocculation


  Aggregation of dispersed globules into loose clusters
• Presence of high charge density on dispersed droplets


  Reduces incidence of flocculation in primary minimum
• Coalescence


  Merging of oil globules in an oil/water emulsion
• Preventing coalescence


  • Presence of mechanically strong adsorbed layer of emulsifier around each globule
  • Condensed mixed monolayer of lipophilic and hydrophilic emulgents
  • Multi molecular film of hydrophilic material
  • Presence of long cohesive hydrocarbon chains projecting into oil phase
• Causes of chemical instability


  • Incompatibility of ingredients
  • Electrolytes causing alteration in energy of interaction or salting out effect
  • Changes in pH
  • Oxidation of oils, fats and emulsifying agents
• Phase inversion


  Emulsion changing from o/w to w/o
• Emulsions from natural sources may introduce heavy microbial contamination
• Microbial contamination can adversely affect physicochemical properties of emulsions
• Adverse storage conditions affecting emulsion stability


  • Temperature affecting viscosity of continuous phase
  • Temperature affecting kinetic motion and collision of dispersed droplets
  • Temperature affecting kinetic motion of emulsifying agent at o/w interface
• Methods of assessing emulsion stability


  • Microscopic examination
  • Globule size analysis
  • Viscosity changes
  • Accelerated stability testing
  • Storage at adverse temperature
  • Centrifugation
• Commercial uses of emulsions


  • Oral
  • Rectal
  • Topical
  • Intravenous feeding
  • Sustained release (IM injection of water soluble drugs)
  • Sustained release multiple emulsions (w/o/w)
• For o/w emulsions


  Decreasing globule size increases bioavailability of drugs
• For w/o emulsions


  Decreasing globule size increases bioavailability of hydrophilic drugs