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PM2C Spring > Nasal Drug Delivery [Vitaliy] > Flashcards

Nasal Drug Delivery [Vitaliy] Flashcards

1
Q

Name the 4 types of cell found in the nasal cavities

A
  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
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2
Q

How does the nasal cavity affect the air breathed in?

A

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

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3
Q

Why does the nose run when someone is ill?

A

Protective mechanism

Gets rid of infection by secreting more mucus

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4
Q

How are particles removed from the nasal cavity?

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

How is mucociliary clearance powered?

A
  • 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
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6
Q

Why is mucociliary clearance necessary?

A

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

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7
Q

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

A

1) Permits the humidification of the inspired air

2) Aids heat transfer

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8
Q

How does mucus affect drug absorption?

A

It presents a barrier to drug absorption

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9
Q

Why may drugs be administered via the nasal route?

A
  • For the alleviation of nasal symptoms (allergy, congestion, infection)
  • Drugs that are inactivated in the GIT following oral administration
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10
Q

Why is the nasal mucosa a unique drug target?

A

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

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11
Q

List 3 common drugs that can be administered nasally

A
  1. Morphone
  2. Nicotine
  3. Insulin
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12
Q

List the advantages of the nasal route

A
  1. Relatively large surface area
  2. Highly vascularised surface = rapid absorption and onset of action
  3. Low metabolic activity
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13
Q

List 3 disadvantages of the nasal route

A
  1. Mucociliary clearance - drug may be cleared before it can be absorbed
  2. Mucus barrier
  3. Limited to potent molecules
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14
Q

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

A
  1. MW of drug molecules
  2. pH of the dosage form
  3. Concentration
  4. Particle size
  5. Tonicity of the dosage form
  6. Viscosity
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15
Q

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

A

Increase in MW causes a massive drop in absorption and bioavailability

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16
Q

What is the role of penetration enhancers?

A

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)

17
Q

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

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

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

18
Q

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

A

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

19
Q

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

A
  • 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
20
Q

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

A

Between 5-10 um

This size tends to deposit in the nasal cavity

21
Q

How do nasal drops work?

A

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

22
Q

How do nasal sprays work?

A

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

23
Q

Are nasal drops or nasal sprays a better dosage form?

A

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
24
Q

How should nasal drops be administered?

A 
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
25
Q

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

A
  1. Enhance nasal absorption
  2. Improve nasal residence time - by reducing clearance
  3. Modify drug structure to change physiochemical properties = very expensive
26
Q

List 5 mechanisms of absorption promotion

A
  1. Alteration of mucus layer
  2. Alteration of tight junctions
  3. Reversed micelle formation
  4. Extraction by co-micellisation
  5. Erosion of mucosal surface
27
Q

How can the mucus layer be altered to promote absorption?

A

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

28
Q

What are cyclodextrins?

A

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

29
Q

What are cyclodextrins used for?

A

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

30
Q

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

A
  • 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
31
Q

List 4 things that liquid nasal formulations commonly contain

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

PM2C Spring (6 decks)

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