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Part 3 – PM3A > (PM3A) Nasal Drug Delivery > Flashcards

(PM3A) Nasal Drug Delivery Flashcards

1
Q

Where is the nasal passage located?

A

Above the oral cavity in the head

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2
Q

What lines the nasal cavity?

A

Mucosal membranes

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3
Q

What types of cell comprise a mucosal membrane?

A

(1) Ciliated columnar cell (cilia + microvilli)
(2) Basal cells
(3) Goblet cells - packed with mucous granules
(4) Non-ciliated columnar cells (microvilli)

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4
Q

Where can ciliated columnar cells be found?

A

Mucosal membranes

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5
Q

Where can basal cells be found?

A

Mucosal membranes

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6
Q

Where can goblet cells be found?

A

Mucosal membranes

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7
Q

Where can non-ciliated columnar cells be found?

A

Mucosal membranes

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8
Q

What temperature does the nose bring inhaled air to?

A

32ºC

Possible from 23-40ºC

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9
Q

What size particles do the vibrisae filter out?

A

Particles >10mcm

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10
Q

What size are the largest particles not removed by the nose via inhalation?

A

2mcm

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11
Q

What size particles are cleared via mucociliary clearance?

A

5-10mcm

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12
Q

What size particles are not filtered by the nasal cavity passages and are able to reach the lungs?

A

<2mcm

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13
Q

What is mucociliary clearance?

A

Dust + microorganisms trapped in a viscoelastic mucous blanket lining the nasal packages

Mucous is rolled by cilia

Cilia beat in a coordinated manner within periciliary fluid

Brought towards nasopharynx

In nasopharynx mucous is swallowed/ expectorated

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14
Q

At what rate is mucous moved in the nasal cavity by cilia?

A

10cm/ min

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15
Q

How long does clearance of the bulk of the mucous in nose take to reach the nasopharynx?

A

~10-20 minutes

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16
Q

What is nasal mucous?

A

Entraps substances entering nasal cavity

Removed via mucociliary clearance

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17
Q

How is inspired air humidified?

A

Using the ability of mucous to retain water

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18
Q

What role does mucous have in drug adsorption?

A

Acts as a diffusion barrier

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19
Q

What types of drug are usually applied using the nasal route?

A

(1) Locally acting to alleviate nasal symptoms

(2) Drugs that are inactivated via the GI tract
- Route can be alternative to IV

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20
Q

What is the only location in the body that provides a direct connection between the CNS and atmosphere?

A

Nasal mucosa

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21
Q

What separates the olfactory bulb from the nasal cavity?

A

Olfactory nerves

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22
Q

Where is the olfactory bulb located?

A

Front brain

Above olfactory nerves

23
Q

What are some advantages of nasal drug delivery?

A

(1) Large surface area for absorption - 160cm^2
(2) Highly vascularised surface - rapid absorption + onset
(3) Low metabolic activity
(4) Good accessibility + easy administration
(5) Some drugs can be absorbed directly into CNS
(6) Can bypass blood brain barrier

24
Q

What are some disadvantages of nasal drug delivery?

A

(1) Mucociliary clearance
(2) Mucous barrier
(3) Some metabolic activity
(4) Limited to potent molecules
(5) Common diseases can alter conditions of nose
(6) Mucosal membranes can be sensitive to irritation

25
Q

What physicochemical factors are of importance in nasal drug delivery?

A

(1) Molecular weight
(2) Particle size
(3) Concentration
(4) pH of dosage form
(5) Viscosity
(6) Tonicity of dosage form

26
Q

What is important about molecular weight when considering nasal drug delivery?

A

<1000 Da

<6000 Da with penetration enhancers

Larger molecules will cause nasal damage

27
Q

What is important about pH when considering nasal drug delivery?

A

Mucous layer is pH5.5-6.5 (slightly acidic)

Absorption of drugs generally increased due to less ionisation

Cationic drugs may be retained by binding to negatively charged mucous glycoproteins

pH can affect peptide absorption with greater complexity

28
Q

What is important about concentration when considering nasal drug delivery?

A

Rate of absorption is affected by concentration of drug in solution at absorbing membrane

Most drugs travel across nasal mucosa via passive diffusion

Highest concentration of drug possible should be chosen

High concentrations of drug used locally for extended periods may cause severe irritation/ adverse tissue reactions

29
Q

Give 2 types of passive diffusion.

A

(1) Transcellular

(2) Paracellular

30
Q

What is important about particle size when considering nasal drug delivery?

A

Smaller particles travel further in the lungs

Larger particles (5-10mcm) tend to deposit in the nasal passage

31
Q

What are nasal drops?

A

Dispersion of a drug solution throughout the length of the nasal cavity (from atrium to nasopharynx)

Relatively large area for immediate absorption

32
Q

What are nasal sprays?

A

Deposit at the front of nasal cavity

Little of the dose reaches the turbinates

33
Q

What are turbinates?

A

Three thin curved shelves of bone in the sides of the nasal cavity

34
Q

How much of the administered dose in a nasal delivery is cleared within 20 minutes?

A

~20%

35
Q

How many stages of clearance are there in nasal delivery

A

2

(1) Fast 20 minute clearance
(2) Slow phase

36
Q

How does the second phase of clearance of nasal delivery differ to the first?

A

Much slower

Clearance of nasal drops is much faster

Clearance of nasal spray is much slower

37
Q

Why does a nasal spray get cleared more slowly in the second phase of nasal clearance?

A

Most of the spray deposits on non-ciliated regions

38
Q

What is a better method to administer rapidly absorbed drugs via the nasal route?

A

Nasal drops as they are cleared much faster

39
Q

Why may a drug be administered as a nasal spray instead of drops?

A

Drugs that diffuse across the nasal epithelium relatively slowly

Require longer contact

40
Q

What is the correct procedure for administration of nasal drops?

A

(1) Lie on back + face up
(2) Lie on back + face left
(3) Lie on back + face right
(4) Lie on back + face up
(5) Sit forward + face down
(6) Sit straight

41
Q

How may drug availability be improved in nasal administration?

A

(1) Enhance nasal absorption
(2) Improve nasal residence time
(3) Modify drug structure to change physicochemical properties

42
Q

Name some mechanisms of absorption promotion in nasal drug delivery.

A

(1) Alteration of mucous layer - surfactants
(2) Alteration of tight junctions - opening using extracellular calcium ions
(3) Reversed micelle formation

(4) Extraction by co-micellisation
- Solubilisation of cell membrane lipids (e.g. cholesterol)

(5) Erosion of mucosal surface

43
Q

What are cyclodextrins?

A

Used to solubilise drugs

Increase concentration of drug driving diffusion at absorption site

44
Q

What are mucoadhesives?

A

Drugs which increase contact time at absorption site

45
Q

Give some examples of mucoadhesives.

A

(1) Bioadhesive solutions/ suspensions

(2) Dry powder bioadhesives

46
Q

What is a bioadhesive solution/ suspension?

A

Water soluble polymers

Decrease rate of mucociliary clearance

Due to high viscosity in solution

47
Q

Give an example of a mucoadhesive used to increase nasal absorption of insulin.

A

Chitosan

48
Q

What is chitosan used for?

A

As a mucoadhesive

To increase nasal absorption
- Particularly of insulin

49
Q

What is a dry powder bioadhesive?

A

Drugs which absorb water upon contact with nasal mucosa

Swell to form viscous gels

Can remain in nasal cavity for up to 6 hours

50
Q

Give some examples of dry powder bioadhesives.

A

(1) Microcrystalline cellulose
(2) Starch
(3) Dextran
(4) Chitosan
(5) Carbomer

51
Q

What types of nasal formulation are there?

A

(1) Nasal spray
(2) Nasal drops
(3) Nasal creams
(4) Nasal powders - not yet developed

52
Q

What is OptiNose?

A

Novel nasal drug delivery device

Intranasal delivery device

For liquid/ powder formulations

53
Q

What do liquid nasal drug formulations often contain (excipients)?

A

(1) Antimicrobial preservatives
(2) Antioxidants
(3) Solubilising agents/ cosolvents
(4) Salts - for pH + tonicity
(5) Humectants - minimise nasal irritation
(6) Viscosity-increasing agents/ mucoadhesive
(7) Absorption enhancer

Part 3 – PM3A (28 decks)

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