L49 - Suspensions and Emulsions 2 (Liquid Dosage Forms)

• List the components of pharmaceutical oral suspensions.

  Vehicle, Buffers, Excipients, Electrolytes, Surfactants, Hydrophilic Polymers, Preservatives, Antioxidants, Sweeteners/flavouring.
• What vehicle is commonly used in oral suspensions?

  Purified water.
• Why are excipients used in suspensions?

  - Physically stabilise suspensions.

  
  

  - Control rate of particle/floccule sedimentation.

  
  

  - To protect suspension from degradation/pathogens.
• Why would we add electrolytes to oral suspensions?

  To control flocculation and decrease zeta potential.
• Why do we add surfactants to oral suspensions?

  
  

  Are ionic or non-ionice preferred?

  
  

  Give an example.

  - Towetparticles and facilitateflocculation(decreasing zeta potential).

  -Non-ionicpreferred (ionic have higher toxicity).

  Eglecithin.
• Why do we add hydrophilic polymers to oral suspensions?

  
  

  How does this work?

  -Stabilisesuspensions: if 2x polymer-coated particles approach each other, they're prevented from getting too close.

  -Increase viscosity:increasing viscositydecreases sedimentation rateandincreases physical stability.

  - One part of the chain adsorbs onto surface of suspended drug particle, remainder of chain in aq vehicle.

  
• Why do we add preservatives to oral suspensions?

  - To prevent growth of pathogenic microorganisms.
• Why do we add antioxidants to oral suspensions?

  So the antioxidants are degraded in place of the drug, toprotect drug from degradation.
• What are the 2 main methods of manufacture for oral suspensions?

  - Direct incorporation. (just add components!)

  
  

  - Precipitation method.
• What does mixing rate impact in direct incorporation?

  
  

  When can we use high speed mixing?

  
  

  When is this not so beneficial?

  Impactsviscosity, sosedimentation rate.

  - High speed mixing if suspension isflocculated.

  - Ifflocculation poor, high speed mixing givesincreased viscosity. Difficult to mix homogeneously.
• How can we optimise particle size of suspended drug?

  - Decrease using a ball mill/milling.

  
  

  - Particle size reduction techniques before adding to vehicle.
• Describe the


  precipitationmethod for manufacturing suspensions.

  What's the main factor we need to control?- Drug dissolved in vehicle prior to precipitation.

  - Add counterion to form insoluble salt.

  - Dissolve excipients in vehicle.

  - Correct volume if needed.

  Controlmixing rate!

  
• What's a potential problem with the precipitation method?

  
  

  How can we resolve this?

  Ionic byproducts may be produced (due to precipitation interactions).

  
  

  - If their [conc] is too high, was precipitated drug with aq solvent.

  
• How can we reduce particle size distribution post-manufacture?

  Using a ball mill.
• What is an emulsion?

  A mixture of immiscible liquids eg oil and water.

  O/W or W/O

  Insoluble liquid is dispersed in a 2nd liquid phase.

  
• What are the 2 phases in an emulsion called?

  Dispersed phase= is subdivided.

  Continuous phase= in which dispersed phase is distributed.

  
• List some uses of emulsions.

  - Topical creams: good viscosity and consistency.

  
  

  - Parenteral nutrition.

  
  

  - Oral administration.

  
  

  - Rectal administrtion of antiepileptics.

  
• Give some


  advantagesof emulsions.- Deliver drugs with low aq solubility via oil droplets.

  
  

  - Taste masking.

  
  

  - Therapeutic effect (soothing on skin).

  
  

  - Reduced irritation after topical administration: drug in internal phase (o/w).

  
  

  - Easier to swallow for children/elderly/dysphagia.
• Give some disadvantages of emulsions.

  - Thermodynamicaly unstable: oil and water separate easily.

  
  

  - Needs surfactants to make it monophasic.

  
  

  - Difficult to manufacture.
• What are 3 types of emulsions?

  - O/W:

  oil = dispersed phase.water = external phase.

  - W/O:

  water = dispersed phase.oil = external phase.

  - Multiple emulsions W/O/W:where dispersed phase contains droplets of another phase.

  
• What defines emulsion type?

  -Stability of droplet phase:

  -Least stablephase coalesces to formexternal phase.

  -How muchof the internal phase isdispersed? (phase volume ration should be ~50% stability).

  -Chemical propertiesof film surrounding internal phase.

  -Viscosityof internal and externl phases.

  
• What do we need to ensure to have an acceptable emulsion/cream?

  - Physical stability: no phase separation.

  
  

  - Flow properties: so it's easily removed from container.

  
  

  - Formulation easily spread (external applications).

  
  

  - Aesthetically/texturally pleasing.

  
  

  - Suitable flavour.

  
  

  - Correct texture for externally applied emulsions.

  
• What are 3 types of test we can use to determine emulsion type eg O/W or W/O?

  1 - Miscibility tests: add oil or water and see which the emulsion is miscible with. Eg W/O emulsions are miscible with oil but not water.

  2 - Staining tests:eg incorporate an oil soluble dye.

  3 - Conductivity tests:water will conduct electricity, oil won't.