Routes of Administration - Aural Nasal

Question 1

What are the typical therapeutic areas for nasal drug delivery?

Answer 1

• Local delivery
  – Nasal allergy
  – Nasal congestion
  – Nasal infection
• Systemic therapy
• Vaccine delivery
• Access to CNS

Question 2

State the advantages of the nasal route.

Answer 2

• Easy to administer.
• Non-invasive, painless.
• Avoids first-pass effect
• Low enzymatic activity
• Direct route to brain is possible
• Potential to elicit a rapid onset of action.
• Newer formulations potentially allow for peptide delivery.

Question 3

Describe nasal anatomy.

Answer 3

• Nasal cavity is divided in to two halves by nasal septum.
• Covered with mucous membrane containing
  goblet cells secreting mucus.
• Absorption occurs across turbinates and septum.

Question 4

How are lipophilic drugs transported?

Answer 4

transcellularly by concentration-
dependent passive diffusion, by receptor/carrier mediated
and vesicular transport mechanisms.

Question 5

How are polar drugs transported?

Answer 5

Polar drugs pass through epithelium via gaps between cells
(tight junctions)

Question 6

Describe the nose brain pathway.

Answer 6

• The olfactory mucosa is in direct contact with the brain and cerebral spinal fluid.

Question 7

Describe the absorption of a drug across the nose brain pathway.
What is this beneficial for?

Answer 7

• Drug could potentially absorbed across the olfactory
  mucosa and enter the CNS.
• Potentially offer a rapid, direct route for drug delivery to the
  brain, bypassing the blood brain barrier.
• Beneficial for treatment of e.g. Parkinson’s disease,
  Alzheimer’s disease or pain.

Question 8

What does the nose function as?

Answer 8

As a passageway for the
movement of air into the respiratory tract, and also as an ‘air-conditioner’ to humidify and warm the air.

Question 9

What happens to large particles in the nasal filter?

Answer 9

They undergo rapid clearance

Question 10

What is important for local and systematic delivery?

Answer 10

The site of particle deposition and the rate of clearance

Question 11

Describe the mucociliary clearance system

Answer 11

Cilia found on the surface of epithelial cells transport mucus 5 mm per min toward the nasopharynx.

Question 12

What is the function of the mucociliary clearance system?

Answer 12

remove foreign
substances from the nasal cavity, and this includes drugs.

Question 13

How do we treat conditions affecting the nose?

Answer 13

deliver directly at
the site of action.

Question 14

What are the advantages of delivering the drug directly at the site of action?

Answer 14

• Permits rapid relief at a much lower dose vs oral
• Reduces systematic side effects e.g. nasal corticosteroids to reduce nasal mucosa inflammation and sinuses without causing pituitary-adrenal suppression

Question 15

When would intranasal delivery be useful?

Answer 15

• In emergency situations where rapid onset of action is required e.g. sumatriptan for migraine and fentanyl for pain relief
• Nasal delivery of peptides e.g. desmopressin acetate which is a pituitary hormone for diabetes insipidus

Question 16

How does solubility affect systematic absorption?

Answer 16

• Drug must be in solution to be absorbed.
• Only 25-200μl of liquid can be administered intranasally.
• Drugs with low aqueous solubility and/or those require a
  high dose pose problems

Question 17

How can solubility potentially be overcome by?

Answer 17

– formulating a suspension or powder in the micro-size
range, but requiring drug to first dissolve in nasal cavity
fluid before absorption.
– Selection of a different salt form of an ionisable drug
– The use of appropriate excipients, e.g. co-solvents.
– Modification of its molecular form

Question 18

How are lipophilic drugs absorbed?

Answer 18

• Rapidly absorbed from the nasal cavity by the transcellular route with bioavailability similar to that of IV

Question 19

How are hydrophilic drugs absorbed?

Answer 19

• Via the paracellular route and this route provided a much smaller area for absorption

Question 20

How does molecular size affect systemic absorption?

Answer 20

• The rate and extent of absorption is inversely proportional to
  the molecular weight of drug.
  – Smaller particles pass on to the lungs.
  – Larger particles impacted on the anterior section and
  run-out of the nose.

Question 21

How does pH affect systemic absorption?

Answer 21

• Formulation pH closes to the nasal mucosa minimises local
  irritation, but pH 3-10 can be tolerated.
• Unionised drug molecules with a higher LogP is better
  absorbed than ionized form.

Question 22

What are possible solutions to enzymatic activity?

Answer 22

– To include enzyme inhibitors in the formulation
– Use of prodrugs to reduce affinity of drug for the enzyme.
– Encapsulate the drug to limit enzyme access to it.

Question 23

How does mucosal contact time affect systemic absorption?

Answer 23

• Increase residence time of drug in turbinates could
  potentially increase drug absorption.
• Increase formulation viscosity increases residence time.
• Increase contact time not necessarily increase absorption.
  – E.g. rate of drug diffusion decreased due to high
  viscosity

Question 24

State the function of mucoadhesive polymers?

Answer 24

Can prolong the drug in contact with the mucosa without themselves being absorbed.

Question 25

What is the function of the mucus layer?

Answer 25

It is a diffusion barrier

Question 26

Compare the permeability of small uncharges molecules to larger cationic molecules.

Answer 26

Small are less affected compared to large

Question 27

State the function of penetration enhancers.

Answer 27

Alter the epithelium structure to temporarily increase permeability

Question 28

What does a typical nasal liquid formulation contain?

Answer 28

– API
– Antimicrobial preservatives (e.g. benzalkonium chloride)
– Antioxidants (e.g. butylated hydroxytoluene)
– Solubilising agents or co-solvents (e.g. glycol derivatives)
– Salts for adjusting pH and tonicity
– Humectants, to minimize irritation to the nose (e.g.
glycerol)
– Viscosity-enhancing agents (e.g. methylcellulose)
– Absorption enhancers

Question 29

What drug treatments are used for the ear?

Answer 29

• Antibiotics
• Anti-inflammatories
• Antiseptics
• Cleansing solutions
• Wax softeners

Question 30

What are the dosage forms available for the ear?

Answer 30

• Drops
• Sprays
• Washes

Question 31

What is ear wax?

Answer 31

A normal bodily secretion which provides a
protective film on the meatal skin.

Question 32

When does ear wax need to be removed?

Answer 32

if it causes deafness or interferes with a proper view of the ear drum.

Question 33

What is ear wax composed of?

Answer 33

mostly lipophilic substances e.g. keratin, lipids, peptides, fatty acids, cholesterol.

Question 34

What are cerumenolytics?

Answer 34

They soften the cerumen and lubricate the canal, thus facilitating ear wax removal from the ear canal
or by disintegrating it.

Question 35

What is otitis externa?

Answer 35

• Inflammatory reaction of the meatal skin.

Question 36

What is otitis externa caused by?

Answer 36

Bacteria or fungus

Question 37

How can otitis externa be treated?

Answer 37

• Thorough cleaning of the ear canal by suction or dry mopping
• Corticosteroid ear drops, astringent solution or acetic acid
  solution can be used.

Question 38

What are astringent preparations?

Answer 38

A substance that causes shrinking or constriction of body tissues, usually locally after topical medicinal application.