L47 - Solutions (Liquid Dosage Forms for Oral Admin)

• List some advantages of oral solutions.

  - Easy toswallowfor children/elderly/dysphagia.

  -Faster therapeutic response:no dissolution step.

  -Homogeneoussystem: uniform distribution. No dose variation.

  -Reduced GI irritation(immediate dilution).

  -Tastemasking
• List some disadvantages of oral solutions.

  - Issues w/ manufacture/transport.

  
  

  - Microorganism growth.

  
  

  - Poorer stability of API/excipients.

  
  

  - Shorter shelf life (t95).

  
  

  - May need refrigeration.

  
  

  - Dose accuracy (can the pt measure correctly?).

  
  

  - Taste.

  
  

  - Unsuitable for drugs that are chemically unstable in water.
• What are the main challenges when developing oral solutions?

  - Homogeneity in formulation.

  
  

  - Aqueous solubility of drug.
• How does aqueous solubility affect pH of formulation?

  
  

  Eg if it's high/moderate/low?

  High- readily incorporated into vehicle.

  Moderate- need to enhance solubility eg through use of cosolvents.

  Low- choose alternative dosage form!
• What's the most common vehicle for oral solutions?

  Purified Water!

  
  

  - Low cost.

  - Low toxicity.

  
  

  - NOT tap water: chemical incompatibilities.

  
  

  - NOT to be used for parenteral (outside GI tract) formulations as not sterile.
• How can we increase drug solubility within the formulation?

  -Cosolventseg glycerol/glycerin, alcohol.

  -Surfactantsand complexation.

  
• Name 3 major excipients in oral solutions.

  Buffers, Sweetening Agents and Viscosity enhancing agents.
• Why do we need buffers?

  
  

  What are some common buffers used?

  To control pH of solution.

  Egacetates, citrates, phosphates.
• Why do we use sweetening agents?

  
  

  Examples?

  To increase palatability (increase compliance).

  Egsucrose, sorbitol, saccharin sodium, aspartame.

  
  

  NB - be aware of children/diabetes mellitus.
• Name some viscosity enhancing agents.

  Cellulose derivatives eg methylcellulose (non-ionic).

  Sodium alginate (Ionichydrophilic polymers)
• What is the role of antioxidants in oral solutions?

  
  

  Give an example of a commonly used antioxidant.

  - Increase stability of drugs susceptible to chemical degradation by oxidation.

  - Higher oxidative potential than the drug.

  Egascorbic acid.

  
• How do antioxidants work?

  - Oxidised (degraded) in place of the drug, so protect drug from decomposition.

  
• What is the purpose of preservatives?

  
  

  Name some ideal preservative properties.

  Control microbial growth.

  
  

  - Broad spectrum antimicrobial activity. (combines gram +ve/-ve).

  
  

  - Chemically + physically stable (over t95 of product).

  
  

  - Low toxicity.

  
• What factors affect preservative efficacy in oral solutions?

  - pH of formulation.

  
  

  - Micelle presence.

  
  

  - Hydrophilic polymer presence.
• How does formulation pH affect preservative efficacy?

  - Antimicrobial properties change with un/ionised fraction of species.

  
  

  - Neutral conditions allow preservative to dissociate.

  
  

  - Use Hendersson-Hasselbalch to calculate fraction of acidic preservative at a particular pH.
• How does micelle presence affect preservative efficacy?

  - Increases solubilisation of lipophilic drugs.

  
  

  - Affects preservative [conc].

  
  

  - Lipophilic species may partition into micelles, decreasing available [preservative] conc in solution.

  
  

  - Equilibrium is disrupted.

  
  

  - Must increase [preservative] conc to ensure free preservative is >MIC (minimum inhibitory conc).
• How does hydrophilic polymer presence affect preservative efficacy?

  - Free [preservative] decreases in the presence of hydrophilic polymers eg methylcellulose.

  
  

  - Preservatives can react w/dissolved polymer.

  
  

  - Need to increase preservative conc in formulation again.
• How are pharmaceutical oral solutions manufactured?

  - Dissolve solutes in solvent.

  
  

  - Filter!

  
  

  - On industrial scale, large mixing vessels are thermostatically controlled and order of adding components is fixed.
• Name the 3 main types of pharmaceutical oral solutions.

  Solutions, Syrups, Elixirs.
• Briefly summarise qualities of pharmaceutical oral

  solutions.- Good for systematic absorption of drug.

  
  

  - Formulated over broad pH range.

  
  

  - All components should be soluble, with no evidence of precipitation.

  
  

  - Usual pH ~7.
• Briefly summarise qualities of pharmaceutical

  syrups.- Highly concentrated, aqueous solutions of sugar w/flavouring.

  
  

  - Contain purified water, sugar (eg succrose) OR artificial sweeteners, natural/synthetic flavourings and colourings.
• Briefly summarise qualities of pharmaceutical

  elixirs.- Clear solutions.

  
  

  - HIGH [alcohol] conc sufficient to ensure all other components remain in solution.

  
  

  - Preservatives NOT required in elixirs with >12& v/v alcohol bc you wouldn't expect microbial growth.