(PM3A) Nasal Drug Delivery Flashcards
(46 cards)
Where is the nasal passage located?
Above the oral cavity in the head
What lines the nasal cavity?
Mucosal membranes
What types of cell comprise a mucosal membrane?
(1) Ciliated columnar cell (cilia + microvilli)
(2) Basal cells
(3) Goblet cells - packed with mucous granules
(4) Non-ciliated columnar cells (microvilli)
What temperature does the nose bring inhaled air to?
32ºC
Possible from 23-40ºC
What size particles do the vibrisae filter out?
Particles >10um
What size particles are cleared via mucociliary clearance?
5-10um
What size particles are not filtered by the nasal cavity passages and are able to reach the lungs?
<2um
What is mucociliary clearance?
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
At what rate is mucous moved in the nasal cavity by cilia?
10cm/ min
How long does clearance of the bulk of the mucous in nose take to reach the nasopharynx?
~10-20 minutes
What is nasal mucous?
fluid produced by mucosal membrane
Entraps substances entering nasal cavity
Removed via mucociliary clearance
How is inspired air humidified?
Using the ability of mucous to retain water
What role does mucous have in drug adsorption?
Acts as a diffusion barrier
What types of drug are usually applied using the nasal route?
(1) Locally acting to alleviate nasal symptoms
(2) Drugs that are inactivated via the GI tract
- Route can be alternative to IV
What is the only location in the body that provides a direct connection between the CNS and atmosphere?
Nasal mucosa
What separates the olfactory bulb from the nasal cavity?
Olfactory nerves
Where is the olfactory bulb located?
Front brain
Above olfactory nerves
What are some advantages of nasal drug delivery?
(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
What are some disadvantages of nasal drug delivery?
(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
What physicochemical factors are of importance in nasal drug delivery?
(1) Molecular weight
(2) Particle size
(3) Concentration
(4) pH of dosage form
(5) Viscosity
(6) Tonicity of dosage form
What is important about molecular weight when considering nasal drug delivery?
<1000 Da
<6000 Da with penetration enhancers
Larger molecules will cause nasal damage
What is important about pH when considering nasal drug delivery?
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
What is important about concentration when considering nasal drug delivery?
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
Give 2 types of passive diffusion.
(1) Transcellular
(2) Paracellular
