L50 - Emulsions 2 (Liquid Dosage Forms)

• How can emulsions break/crack?

  Flocculation, coalescence, creaming

  
• What is cracking?


  Coalescence of the internal phase.

  
  

  - Emulsion separates into 2 layers.

  
  

  - Irreverisible!

  
  

  - Due to destruction on mono-multilayer film at the interface between the droplet and external phase

  
• What can cause emulsion cracking?

  - Incorrect selection of emulsifying agents.

  
  

  - Presence of incompatible excipients.

  
  

  - Temp.

  
  

  - Microbial spoilage

  
• What happens in flocculation (weak attraction between particles)?

  - Van der Waals forces maintain droplets at a defined distance of separation.

  
  

  - Shaking redisperses droplets to give homogeneous formulation.

  
• What happens if the mechanical properties of the interfacial film are disrupted?

  - Close droplet proximity may cause droplet coalescence to occur.

  
  

  - Film around droplet created from excipients: if this film is disrupted, we can't achieve stability.

  
• Where does flocculation occur on the curve?

  At the secondary minimum.

  
• How can creaming occur?

  
  

  Which phase would you expect to be on top?

  - Results from density difference between oil/water phases.

  
  

  - Involves sedimentation / elevation of internal phase. Produced layer of conc emulsion at top or bottom of container.

  
  

  Eg oil less dense than water, so you'd expect oil to be on top.
• Can we reverse creaming? How?

  Yes - shaking renders emulsion homogeneous.
• How can we prevent creaming?

  If the density difference between the two phases is 0. (density = same)
• How can we reduce creaming rate?

  
  

  What eqn describes creaming rate?

  - Decrease avg. particle size of dispersed phase.

  
  

  - Increase viscosity.

  
  

  Described by Stokes eqn.
• What is phase inversion?

  
  

  When does it occur?

  - Switching O/W to W/O or vice versa.

  
  

  - Occurs when critical value of phase volume ratio has been exceeded.
• What happens to emulsions when you add hydrophilic polymers/surfactant?

  - Surfactants create film around droplets of dispersed phase.

  
  

  - Gel-like multi-layers produced.

  
  

  - Have the baility to adsorb at interphase between disperse and external phase.

  
• What happens to emulsions when you add adsorbed particles?

  
  

  What does the type of emulsion depend on?

  - Addition of finely divided solid particles sufficiently wetted by both phases.

  - Type of emulsion depends on preference of particles for each phase.Egif particles were preferentially wetted by aq phase, = O/W.

  
• What are the typical formulations for Oral/IV and topical emulsions?

  
  

  Which phase determines appearance of emulsion?

  Oral/IV= O/W.

  Topicaleg creams =- O/W for water soluble drugs w/ a local effect; non-greasy.- W/O used for moisturing formulations; greasy.

  External phase determines appearance.
• What factors do we need to consider when manufacturing emulsions?

  -Volumeofinternalphase.(max conc of internal phase = 60% O/W/ 30-40% W/O).

  -Dropletsize.Use milling to reduce droplet size.

  -Viscosityof internal/external phases.Creams have increased viscosity.
• Why would we need to add an emulsifying agent?

  To make phases uniform.
• What do we need to consider when choosing emulsifying agents?

  -Emulsiontype.

  - Clinicaluse+toxicity(eg anionic surfactants are restricted to external formulations).

  -Typeofemulsifyingagent:

  -HLBrequirements of internal phase.
• How can we calculate required HLB of two surfactants?

  HLBmix = x HLBa + (1-x) HLBb

  
• What types of surfactants are used to stabilise emulsion/cream formulations?

  - anionic.

  
  

  - cationic.

  
  

  - non-ionic.

  
  

  - amphoteric
• What excipients are needed in emulsion/cream formulations?

  Aqueous phase:- Vehicle =purifiedwater.-Buffers.

  Oil phase:-veg oil(mono,di,triglycerides and un/saturated fatty acids).

  - needPRESERVATIVESas water is external phase, so capacity for microbial growth.
• How are emulsions/creams manufactured?

  - Dissolution of oil-soluble components (oil phase).

  
  

  - Dissolution of water-soluble components (aq phase).

  
  

  - Turbulent mixing conditions!

  
• What equipment is used to produce emulsions at lab scale/ production scale?

  Lab = mechanical stirrers.

  
  

  Production scale = mechanical stirrers, homogenisers, ultrasonifiers, colloid mills.

  
• What's the optimum phase:volume ration for emulsions?

  50:50