Sublingual, buccal and rectal drug delivery

Question 1

What are the two oral transmucosal forms of delivery?

Answer 1

Sublingual and buccal

Question 2

What are the layers of the oral mucosa?

Answer 2

• Epithelium
• Basement membrane
• Lamiina propria

Question 3

State the layers of the oral mucosa:

Answer 3

• Epithelium
• Basement membrane
• Lamiina propria

Question 4

Why is paracellular absorption limited by the oral submucosa?

Answer 4

Epithelial thickness in addition to multiple cell layers makes the oral mucosa less permeable to paracellular-pathway drugs.

Question 5

Why is transcellular absorption preferred for sublingual and buccal drug delivery?**

Answer 5

Epithelium is highly permeable since it is thin and has a good blood supply.

Question 6

Why do you get more paracellular absorption in the mouth than in the GI tract?

Answer 6

Intracellular lipids in the oral epithelia allow for lipophilic drugs to diffuse more easily between cells.

Question 7

Which has a better blood supply? Buccal or sublingual?

Answer 7

Buccal

Question 8

Explain how the oral mucosal blood supply makes it a good target for drug absorption:

Answer 8

• Extensive blood supply steepens drug concentration gradient for absorption
• Oral mucosal blood supply avoids hepatic first-pass metabolism

Question 9

What factors of the drug must be considered when debating oral mucosal drug delivery?

Answer 9

• Residence time
• Taste
• Irritation
• Compliance

Question 10

Why must residence time be accounted for when debating oral mucosal drug delivery?

Answer 10

If the drug has a long residence time, then it will remain in the mouth for longer, providing more opportunities for it to be ingested.

Question 11

How does saliva positively and negatively impact oral mucosal drug absorption?

Answer 11

• [Positive] Saliva aids drug dissolution
• [Negative] Saliva washout can reduce sublingual and increase oral drug absorption

Question 12

What is saliva washout? How does this impact submucosal drug absorption?

Answer 12

The swallowing of saliva and dissolved substances (drugs) due to heightened saliva production.

It decreases submucosal drug absorption.

Question 14

Explain how mucus affects submucosal drug absorption:

Answer 14

Mucus increases epithelial thickness, thereby lengthening the diffusion pathway and decreasing rates of absorption.

Mucus is negatively charged and thus will repel negatively charged drugs; reducing their submucosal absorption.

Question 15

Name some oral transmucosal delivery systems. What type of release do they permit?

Answer 15

Lozenge - Quick
Tablet - Quick/Controlled
Spray - Quick
Film - Quick
Gum - Quick

Question 16

Using nitroglycerin as a case study, explain why sublingual drug delivery is desirable for immediate therapy.

Answer 16

• Nitroglycerin is a treatment for angina (chest pain)
• Sublingual nitroglycerin is quickly absorbed and quickly reaches therapeutic levels in circulation
• Thus, outbreaks of angina can be rapidly treated, reducing the chest pain

Question 17

Explain why sublingual opioid delivery is beneficial for break-out cancer pain compared to traditional opioid treatments:

Answer 17

• Traditional opioid treatments are absorbed slower
• Thus, therapeutic levels reached after the pain episode
• Sublingual opioids are absorbed quicker
• Therapeutic levels reached before pain peak

Question 18

Summarise the advantages of oral mucosal delivery:

Answer 18

• Good access and ease of use
• Good relative surface area
• Rich blood supply
• Low metabolism (saliva)
• No first pass (bypasses liver)

Question 19

Summarise the disadvantages of oral mucosal delivery:

Answer 19

• High MW drugs must be potent
• Saliva and mucus reduce absorption
• Patient acceptance (no food/swallowing)
• Development cost

Question 20

Why is patient acceptance a problem with oral mucosal drugs?

Answer 20

To avoid oral absorption, some drugs require that you minimise swallowing and therefore avoid eating. Some patients may not comply.

Question 21

Why must high MW drugs be potent if they are being absorbed by the oral submucosa?

Answer 21

Saliva washout impacts higher MW drugs more than lower MW drugs. This must be accounted for by being sufficiently potent.

Question 22

For what types of patients is rectal drug administration beneficial?

Answer 22

• Unconscious patients
• Children
• Nauseous/vomiting patients
• Patients with upper GI diseases

Question 23

What drug features may make rectal drug administration preferable?

Answer 23

• Bad-tasting drugs
• Drugs heavily degraded by oral delivery

Question 24

Name some of the different types of rectal dosage forms:

Answer 24

• Suppositories
• Capsules
• Tablets
• Ointments/creams/gels
• Solutions/suspensions/emulsions

Question 25

How does the structure of a suppository aid its function?

Answer 25

Fatty/waxy base melts at body temperature, improving dissolution and absorption.

Question 26

How does the rectal anatomy favour transcellular absorption?

Answer 26

The epithelium is one cell thick. The short diffusion distance is ideal for the transcellular pathway.

Question 27

Which method of absorption is better in the rectum? Why?

Answer 27

Transcellular absorption since the rectal epithelium is one cell thick.

Question 28

Why is rectal drug delivery described as somewhat avoiding the hepatic first-pass effect?

Answer 28

- Blood supply for the lower region avoids first-pass (not sent to liver) - Blood supply for the upper region contributes to the portal vein, experiencing first-pass

Question 29

Summarise the main advantages of rectal drug delivery:

Answer 29

- Safe and painless - Avoids GI drug degradation - Largely avoids hepatic first-pass - Alternative when oral delivery infeasible - Protein-based drug delivery

Question 30

Why can protein based drugs be delivered rectally but not orally?

Answer 30

Oral delivery involves pepsin enzymes unlike rectal delivery.

Question 31

Summarise the main disadvantages of rectal drug delivery:

Answer 31

- Patient acceptability (esp long-term) - Potential for hepatic first-pass - Leakage - Slower absorption than oral and IV

Question 32

Explain why rectal drug delivery is arguably more viable than other first-pass avoidant methods:

Answer 32

Other methods of drug delivery such as IV require a medical professional. Rectal delivery can be carried out by carers independently.