Solutions 3

• What is a major improvement in drug solubility?

  Forming a salt

  
• Which salts can be formed from acidic drugs?

  Sodium, potassium, calcium salts
• Which salts can be formed from basic drugs?

  Hydrochloride, sulphate, tartrate salts
• Why is the dissolution rate of weakly acidic drugs low in GI fluids?

  Because the pH is low (1-3)

  
• How can increasing pH in the diffusion layer affect drug solubility?

  It would increase solubility in this layer

  
• How can the pH in the diffusion layer be changed?

  By changing the drug from free acid to basic salt

  
• What happens to the dissolution of a basic salt form of a weakly acidic drug in gastric fluids?

  It dissolves rapidly and is absorbed

  
• What is an example of a drug absorbed faster as a sodium salt?

  Naproxen sodium

  
• How do hydrochloride ions affect the pH of the diffusion layer for weakly basic drugs?

  They lower the pH, increasing drug solubility

  
• Why is precipitation of free base avoided in the small intestine?

  Because absorption occurs rapidly
• Why might a salt be chosen to decrease solubility?

  To reduce bitter taste in formulations
• What was the previous formulation of Floxapen Syrup Forte?

  Na salt
• How did reformulating Floxapen Syrup Forte with Mg salt affect its taste?

  It reduced the bitter taste
• What is the common ion effect?

  Adding a common ion reduces solubility
• What happens when either A+ or B- is increased in a slightly soluble electrolyte?

  It pushes the equilibrium to the left
• What is the effect of adding hydrochloride salts in body fluids?

  It increases Cl- ions, reducing solubility
• What is salting in?

  Increased apparent solubility of nonelectrolytes
• What is salting out?

  Decreased apparent solubility of nonelectrolytes
• How do highly-hydrated electrolytes affect solubility?

  They reduce the amount of water available
• What is the role of complexation in drug solubility?

  It forms soluble macromolecule complexes
• What is an example of a complex formed with povidone iodine?

  Complex of iodine and polyvinylpyrrolidone
• Why must complex formation be reversible?

  To allow crossing of membranes
• What is the structure of cyclodextrins?

  Hollow cylindrical molecules of glucose units
• How many glucose units does α-cyclodextrin have?

  6 units
• How do cyclodextrins improve drug dissolution?

  By forming inclusion complexes with drugs
• What is the hydrophobic property of cyclodextrins used for?

  To accumulate poorly soluble drugs
• What is the pharmaceutical relevance of cyclodextrins?

  They improve the rate and extent of dissolution
• What are the applications of cyclodextrins in pharmaceuticals?

  • Sporanox: itraconazole with hydroxypropyl-β-cyclodextrin
  • Menagargle: iodine with β-cyclodextrin
  • Nicorette Microtab: nicotine with β-cyclodextrin
  • Viridal: alprostadil with α-cyclodextrin
• How does the salt form of a weakly acidic drug affect dissolution?

  • Increases pH in the boundary layer
  • Increases dissolution and solubility

  
• What are the effects of salting in and salting out in drug formulations?

  • Salting in: increases solubility
  • Salting out: decreases solubility

  
• What is the significance of complexation in drug formulation?

  • Forms soluble macromolecule complexes
  • Can enhance or hinder bioavailability
• What are the characteristics of cyclodextrins?

  • Hollow cylindrical molecules
  • Made of glucose units
  • Form inclusion complexes with drugs