L51 - Role of Excipients

• List some reasons NOT to administer a pure drug.

  -Dose: hard to measure small quantities.

  -Taste.

  -Physicalproperties: solubility, partitioning, bioavailability, stability.

  - To controlabsorptionrate.

  - To allowhandling,transportationandmarketing.

  - To allowadministrationvia specific routes.

  
• What kind of qualities make drugs hard to formulate?

  - High dose, low potency.

  
  

  - Poor flow/compressibility.
• What excipient commonly gives effervescence in effervescent tablets?

  Sodium bicarbonate, NaHCO3.

  
• What is the mode of action of NaHCO3 as a disintegrant?

  - Increases rate of tablet disintegration, dissolution and gastric emptying.
• What is an excipient?

  
  

  What qualities must it have?

  
  

  What issues might a pt have with some excipients?

  All components other than API.

  
  

  - Must be chemically and physiologically inert.

  
  

  - Moral/religious issues eg gelatin.
• Name some uses for excipients.

  - Aids systemprocessingduring manufacture.

  - Protects, supports or enhancesstability/bioavailability/acceptability.

  - Assists in productidentification.

  - Enhancessafety/efficacyduring storage/use.
• Name some common pharmaceutical excipients.

  - Lactose/microcrystalline cellulose: diluent, compressive.

  
  

  - NaHCO3: effervescent.

  
  

  - Mg stearate: lubricant.

  
  

  - Colloidal silicon dioxide.
• What's an issue with using Mg stearate as a lubricant?

  - Mg stearate imparts hydrophobicity whichinhibitsdissolution.

  - Need to minimise % of lubricant in a solid dosage form as it can impact tableting.
• What are diluents?

  
  

  Give examples of 3. How relatively hygroscopic are they?

  Bulking agents/fillers.

  = Inert substances added to API to make tablet.

  EgLactose- good taste, rapidly dissolves in water, not hygroscopic.

  Dicalcium phosphate -wet granulation, insoluble in water, less hygroscopic.

  Starches -very hygroscopic, <14% moisture uptake.

  
• What is Microcrystalline cellulose?

  
  

  How is it produced?

  - Cellulose derivative common in pharmaceutics.

  
  

  - Produced by partial hydrolysis of cellulose.
• Name some properties of microcrystalline cellulose.

  
  

  What is it sensitive to?

  - Good compressibility.

  
  

  - High strength from low compression forces.

  
  

  - Some disintegration properties.

  
  

  - Moisture sensitive.

  
  

  - Lubricant sensitive: lubricant hinders strong bonds forming between layers, weakening tablet.

  
• Name and describe the 3 grades of Microcrystalline cellulose.

  Low moisture grade- reduced compression.

  Higher bulk density- aids blending.

  Low bulk density- increases tablet strength.

  
• Describe the role of lubricants.

  
  

  What's the most effective punch/die lubricant?

  - Prevent adherence to surfaces.

  - Ensure smooth ejection of tablet from die.

  - Anti-adherents and flow aids.

  Eg most effectivepunch lubricants:talc/ Mg stearate.

  Die lubricants:stearic acid.

  
• How do we use Magnesium Stearate?

  - Most popular tabletting lubricant.

  
  

  - Incorporated w/ dry granules before compression.

  
  

  - Thin layer of Mg stearate around granules just as effective as thick layer.

  
  

  - Self-lubricating properties.

  
• List some disadvantages of using Mg Stearate.

  - Needsadditional processingsteps.

  - Increased [Mg stearate] concdecreases disintegrationtime/dissolutionand weakens bonding forces.

  - Reduction due to its hydrophobic nature may occur.

  -Incompatiblew/ many drugs due to interactions with API.
• Why do we add glidants/flow agents to tablets?

  
  

  What's the most common/effective glidant?

  To improve flow properties.

  Fumed silica.

  
• Describe the action of flow agents.

  - Reduce interparticle friction.

  
  

  - Reduction in contact area between granules reduces the interparticulate cohesion/adhesion, which determines flowability.
• What is the role of disintegrants?

  - Promote tablet dissolution in vivo.

  
  

  - Largely important in dissolution of insoluble drugs, eg those with a high dose.

  
  

  - Disintegrates tablet to increase SA for rapid release from dosage form.

  
• Name some of the most common disintegrants.

  Starch, PVP, modified starchesandcellulose materials.

  
• What is the purpose of disintegration and deaggregation?

  Increases SA of drug to increase dissolution rate

  
• List some mechanisms of disintegrant action.

  -Swelling.

  -Porosity and capillary action(draws liquid into capillary pathways and ruptures interparticle bonds).

  -Deformation.

  -Gas production.

  - Aninter-relationshipoccurs in most formulations.

  
• Describe Super-disintegrants, and give an example.

  Eg modified starch = sodium starch glycollate.

  
  

  - Rapid, extensive swelling.

  
  

  - Minimum gelling.

  
  

  - More effective at low [conc] (4-6%).

  
  

  - Reducing issues relating to compressibility and flowability of starch.

  
  

  - More hygroscopic.
• What is the role of binding agents?

  
  

  What must be removed prior to compression?

  - Bind powders in wet granulation, or bind granules in direct compression.

  
  

  - Liquid additives must be removed prior to compression.
• What can binding agents be added as?

  - Powder in a formulation.

  
  

  - Solution to the mixed powders in wet granulation.
• Give examples of some binding agents.

  Starch/gelatin/PVP.

  PVP is soluble in water and alcohol, and releases the drug rapidly.
• What are adsorbents?

  
  

  What is their role?

  = Substances capable of holding fluids in a dry state.

  
  

  - Protects tablet from humidity.
• Give examples of adsorbents.


  Kaolin, fumed silica, MgCO3, microcrystalline cellulose.