disperse systems 3

• Physical stability of emulsions

  Why it is important
• Total parenteral nutrition


  • Delivers lipids intravenously
  • Pure lipids cannot be administered to the blood stream as they are immiscible and won't form droplets that are small enough
  • Large droplets can cause emboli (blockage of blood vessels)
  • Formulated in o/w emulsion with carefully controlled droplet size
  • Physical instability during storage and aggregation of droplets can be fatal
• Properties that affect stability

  • Kinetic properties (movement of disperse phase)
  • Viscosity of the disperse system
  • Electrical properties ('particle'/'particle' and 'particle/liquid interaction')
  • Interfacial energy ('particle'/'particle' and 'particle/liquid interaction')
• Surface and interfacial tension

  • In bulk of liquid equal attractive forces between molecules
  • At surface there is a net inward attraction of molecules
  • Behaviour of molecules at interface different from molecules in bulk phase
  • Interfacial behaviour influences whether two phases will form a disperse system and once formed whether the disperse system is stable
• Interfacial tension


  One of two key properties that influence behaviour
• Interfacial free energy


  One of two key properties that influence behaviour
• Micelles formation


  Influenced by surface and interfacial tension
• Liquid/solid interaction


  • Measured by contact angle goniometry
  • Drop of liquid placed on solid surface may either spread completely = affinity (θ < 90°) or form a drop = no affinity (θ > 90°)
  • If the liquid is water: spread = hydrophilic solid, drop = hydrophobic solid
• Liquid/solid interface applications


  • Meniscus (e.g. water. Molecules of liquid attracted to container)
  • Contact lenses (insertion of lens and comfort)
  • Wetting and cleaning solutions
  • Wetting of powders (preparation of suspensions)
  • Tablet granulation
  • Tablet film coating
• Liquid/liquid interface


  Cohesive forces between molecules of the same phase (F_C) vs adhesive forces between molecules of different phases (F_A)

  If F_A < F_C, the interfacial tension is high and can be reduced with a tensioactive (surfactant)

  If F_A = F_C, the interfacial tension is low and the phases will disperse one into the other

  The F_A / F_C balance determines the interfacial tension
• Types of surfactants


  • Ionic: cationic, anionic, zwitterionic (amphoteric)
  • Non-ionic
• Combination of surfactants


  In many cases a combination is best

  Example: Emulsifying wax BP - sodium lauryl sulfate (anionic) + cetostearyl alcohol (non-ionic)

  Charged 'heads' at O/W interface repel each other, non-ionic surfactants get between ionic molecules, hence greater number of surfactant molecules at interface giving better stability
• Emulsion instability


  • Cracking: rupture of interfacial film leading to the coalescence of droplets in the disperse phase until complete and irreversible separation of the two phases
  • Creaming: due to a difference in density between the two phases. Mainly in O/W emulsions; oil droplets move upwards and accumulate at the surface. This is reversible by shaking the emulsion
  • Phase inversion: the disperse phase becomes the continuous phase, and vice versa. Phase inversion can be caused by a large disperse phase, temperature changes and dirty equipment or charge interactions
  • Flocculation: clumping together of droplets to form loose aggregates. This is reversible by shaking
• Hydrophile-lipophile balance (HLB)


  System used to characterise surfactant function

  Gives an indication of its relative polarity
• HLB ranges for different surfactant functions

  • Antifoaming agents (2 – 3)
  • Water in oil emulsifying agents (3 – 6)
  • Wetting and spreading agents (7 – 9)
  • Oil in water emulsifying agents (8 – 16)
  • Detergents (13 – 15)
  • Solubilising agents (15 – 18)
• Some pharmaceutical surfactants


  • Sorbitan trioleate (Span 85) - HLB 1.5
  • Oleic acid - HLB 4.3
  • Sorbitan monostearate (Span 60) - HLB 4.7
  • Polysorbate 80 (polyoxyethylene sorbitan mono-oleate) (Tween 80) - HLB 15.0
  • Potassium oleate - HLB 20.0
  • Sodium dodecyl (lauryl) sulphate - HLB 40.0
• HLB of mixed surfactants


  Combined HLB = x HLB_A + (1 - x) HLB_B

  Where x = mole fraction
• Formulating an oil in water emulsion


  Step 1: Calculate the total percentage of oil phase

  Step 2: Calculate the percentage of each lipophilic compound in the oil phase

  Step 3: Calculate the overall required HLB value for the combination of lipids used

  Step 4: Calculate the % of two surfactants that would give you the required HLB
• The physicochemical basis of pharmaceuticals. Moynihan and Crean Pages 156 - 192
• Pharmaceutical Practice, 5th ed. Chapters 35 (p329) and 36 (p 337 - only some sections)
• Aulton's Pharmaceutics: The design and manufacture of medicines. Aulton for background information only!