Nasal Drug Delivery [Vitaliy]

Question 1

Name the 4 types of cell found in the nasal cavities

Answer 1

1. Ciliated columnar cells - covered by cilia and microvilli of uniform length
2. Basal cells (short)
3. Goblet cells - packed with mucus granules
4. Non-ciliated columnar cells - covered by microvilli of uniform length

Question 2

How does the nasal cavity affect the air breathed in?

Answer 2

It brings the air to a temperature which is acceptable for the body
Has to produce more moisture when it’s cold to humidify and warm the air = more mucus

Question 3

Why does the nose run when someone is ill?

Answer 3

Protective mechanism

Gets rid of infection by secreting more mucus

Question 4

How are particles removed from the nasal cavity?

Answer 4

• Particles > 10um = filtered out by the vibrisae in nostrils
• Smaller particles (5-10um) = deposit in nasal passages and cleared by mucociliary clearance
• Particles

Question 5

How is mucociliary clearance powered?

Answer 5

• The mucus is propelled by the tips of the cilia, beating in a co-ordinated manner within the periciliary fluid
• It travels towards the nasopharynx where it is swallowed or expectorated

Question 6

Why is mucociliary clearance necessary?

Answer 6

Dust and micro-organisms get entrapped within the viscoelastic mucus blanket lining the nasal passages

Question 7

What does mucus’s capacity to hold water enable it to do?

Answer 7

1) Permits the humidification of the inspired air

2) Aids heat transfer

Question 8

How does mucus affect drug absorption?

Answer 8

It presents a barrier to drug absorption

Question 9

Why may drugs be administered via the nasal route?

Answer 9

• For the alleviation of nasal symptoms (allergy, congestion, infection)
• Drugs that are inactivated in the GIT following oral administration

Question 10

Why is the nasal mucosa a unique drug target?

Answer 10

It is the only location that provides a direct connection between the CNS and the atmosphere

Question 11

List 3 common drugs that can be administered nasally

Answer 11

1. Morphone
2. Nicotine
3. Insulin

Question 12

List the advantages of the nasal route

Answer 12

1. Relatively large surface area
2. Highly vascularised surface = rapid absorption and onset of action
3. Low metabolic activity

Question 13

List 3 disadvantages of the nasal route

Answer 13

1. Mucociliary clearance - drug may be cleared before it can be absorbed
2. Mucus barrier
3. Limited to potent molecules

Question 14

List 6 factors which affect the formulation of a drug to be delivered via the nasal route

Answer 14

1. MW of drug molecules
2. pH of the dosage form
3. Concentration
4. Particle size
5. Tonicity of the dosage form
6. Viscosity

Question 15

How does the molecular weight of a drug affect its administration via the nasal route?

Answer 15

Increase in MW causes a massive drop in absorption and bioavailability

Question 16

What is the role of penetration enhancers?

Answer 16

Mean that larger molecules can be absorbed in the nasal cavity than would otherwise be possible (up to 600 Da compared to just 100 Da)

Question 17

How does pH affect a drug’s administration via the nasal route?

Answer 17

• Mucus layer is slightly acidic (pH 5.5-6.5)

- Absorption of drugs is generally increased - they become less ionised

Question 18

Why may cationic drug molecules find it more difficult to pass through the nasal membrane?

Answer 18

When in ionised form they can be retained through binding to negatively charged mucus glycoproteins

Question 19

How does concentration affect a drug’s administration via the nasal cavity?

Answer 19

• In the majority of cases, absorption across the nasal mucosa is via passive diffusion (para or transcellular)
• Rate of absorption is affected by the concentration of the drug at the absorbing membrane

Question 20

What is the best particle size for drug molecules to be absorbed in the nasal cavity?

Answer 20

Between 5-10 um

This size tends to deposit in the nasal cavity

Question 21

How do nasal drops work?

Answer 21

They disperse a drug solution throughout the length of the nasal cavity = large area for immediate absorption

Question 22

How do nasal sprays work?

Answer 22

They tend to deposit at the front of the nasal cavity with little of the dose reaching the turbinates

Question 23

Are nasal drops or nasal sprays a better dosage form?

Answer 23

Depends on the drug

• Drops are cleared and absorbed faster so will be good for drugs which can be rapidly absorbed
• Sprays are absorbed more slowly so is suitable for drugs which take some time to diffuse across the nasal epithelium

Question 24

How should nasal drops be administered?

Answer 24

Lying on back for (30 secs)
Then turn head to right for (30 secs)
Then to the left for (30 secs)
Then neck bent forwards for (30 seconds)
Then sat upright
This ensures a complete coating of the nasal mucosa from the atrium to the nasopharynx

Question 25

List 3 ways that drug availability can be improved in nasal administration

Answer 25

1. Enhance nasal absorption 2. Improve nasal residence time - by reducing clearance 3. Modify drug structure to change physiochemical properties = very expensive

Question 26

List 5 mechanisms of absorption promotion

Answer 26

1. Alteration of mucus layer 2. Alteration of tight junctions 3. Reversed micelle formation 4. Extraction by co-micellisation 5. Erosion of mucosal surface

Question 27

How can the mucus layer be altered to promote absorption?

Answer 27

Use agents that decrease the viscoelasticity of mucus = anionic and cationic surfactants

Question 28

What are cyclodextrins?

Answer 28

Sugar molecules of circular structure Produced from starch Hydrophilic outside and hydrophobic inside

Question 29

What are cyclodextrins used for?

Answer 29

To solubilise drugs = increase the concentration of drug driving the diffusion at the absorption site

Question 30

Explain the use of mucoadhesives to increase contact time at the absorption site

Answer 30

- Bioadhesive solutions/suspensions - decrease rate of mucociliary clearance - Dry powder bioadhesives - absorb water upon contact with nasal mucosa = viscous gels = can stay in nasal cavity for up to 6 hours

Question 31

List 4 things that liquid nasal formulations commonly contain

Answer 31

1. Antimicrobial preservatives = benzalkonium chloride 2. Absorption enhancers 3. Viscosity-increasing agents = methylcellulose (polymer) 4. Antioxidants