Buccal Mucosal Drug Delivery

Question 1

List SEVEN advantages of buccal mucosal drug delivery.

Answer 1

1. Non-invasive
2. Convenient
3. Rapid onset of action
4. Avoidance of first pass metabolism
5. The drug is not exposed to GI fluids
6. High patient acceptance
7. Low proteolytic activity

Question 2

List FOUR challenges of buccal mucosal drug delivery.

Answer 2

1. Small size of the oral cavitiy
   
   1. Means limited drug amount can be used
2. Limited surface area of oral cavity (approx. 100cm²)
   
   1. Possible less absorption
3. Low permeability compared with small intestine
   
   1. Due to its multi-layered epithelium (stratified squamous) in the mucosa
4. Limited volume of liquid in oral cavity (~1 mL)
   
   1. Dissolution issue for water-soluble drugs

Question 3

List FOUR requirements of the drug to be absorbed via buccal mucosal layer.

Answer 3

1. Adequate potency (therapeutic dose below approx. 100mg)
2. Sufficient dissolution rate (good solubility)
3. Good/neutral taste
4. Sufficient permeability (Log P)

Question 4

“The epithelium of the oral mucosal strucue is stratified squamous.” What does this mean and what does it imply?

Answer 4

This means that the oral mucosae is multi-layered and is considered either keratinised or non-keratinised depending on function.

Question 5

Name the three types of mucosa in the oral cavity and their degree of keritinisation.

Answer 5

1. Masticatory mucosa
   
   1. Keratinised - resistant to abraision (therefore involved in chewing)
2. Lining​ mucosa
   
   1. Non-keratinised - Flexible; therefore lines the elastic regions of the mouth used for speaking, eating, etc.
   2. Sublingual & buccal mucosa
3. Specialised mucosa
   
   1. Keratinised AND Non-keratinised mixture - Tongue

Question 6

What are the THREE factors affecting drug permeability in oral mucosa?

Answer 6

1. Extent of keratinization
2. Tissue thickness
3. Physicochemical properties of the drug

Question 7

Compare the route of drug permability between non-keratinised mucosa and the small instestine

Answer 7

• Small intestine has only one layer of epithelial cells, thus drugs can permeate via the transcellular route
• Non-keratinised mucosa has a stratified squamous (multi-layered) of epithelial cells, thus drugs will have better permeability via the paracellular route

Question 8

List FOUR barriers that a drug absorped via the non-keratinised mucosa avoids when compared to Small instestine absorption.

Answer 8

1. Must avoid acidic conditions of the stomach
2. Must stay soluble within the intestine & have the right pKa
3. Not be a substrate of efflux tranporters like p-Gp
4. Not be a substrate of cytochrome p450 enzymes in the liver

Question 9

Compare and explain the structural differences between a keratinised and a non-keratinised mucosa.

Answer 9

• Keratinised mucosa:
  
  • _​L_ined with keratin-filled cells
  • Intercellular lipids are more ordered
  • Intercellular lipids are non-polar
• Non-keratinised mucosa:
  
  • Intercellular lipids are in a less ordered (amorphous) state
    
    • more spaces = easier penetration
  • Intercellular lipids are polar

Question 10

“Buccal mucosa achieves a more rapid absorption than sublingual mucosa” True or False. What factor justifies your answer?

Answer 10

• False.
• More rapid absorption is expected through sublingual mucosa, despite both being non-keratinised.
• This is because the tissue thickness of the sublingual mucosa is around 200 um (20-30 cell layers), whereas buccal mucosa is around 500 um (40-50 cell layers)

Question 11

What THREE physicochemical properties is required for drug permeability into the oral mucosa?

Answer 11

1. Molecular weight
   
   1. < 500 Da
2. Lipophilicity
   
   1. Log D_7.4 = 1 - 3
      
      1. can’t be too lipophilic, otherwise it won’t dissolve or just get stuck in the membrane
3. Extent of ionization
   
   1. Non-ionised state
      
      1. necessary for permeability.

Question 12

Describe the impact of Azone on estradiol permeability through the buccal mucosa

Answer 12

• Pre-treatment with Azone can significantly enhance buccal uptake and retention of estradiol, thus slowing down release into the circulation.
• Azone:
  
  • Reduces how much estradiol gets across (reducing appearance in receptpr chamber)
  • But, also increases how much is disappearing from donor chamber.
  • Therefore, the Azone enhancer is trapping the estradiol in the tissue (by creating a resevoir) & then slowly releasing estradiol into the receptor chamber = controlled release system for estradiol