L17 - Nasal drug delivery

Question 1

Why is there a need for nasal drug delivery?

Answer 1

• Local delivery of drug:
• nasal congestion
• allergic rhinitis
• localised infection
• Systemic delivery of drug:
• analgesics (for migraine)
• hormones
• Vaccine immunisation by delivering antigen to the Nasal Associated Lymphoid Tissue (NALT)
• Potential for direct delivery to CNS - target for Alzheimer’s disease…

Question 2

Why is the nasal cavity good for drug delivery?

Answer 2

Volume = 12 - 15ml

Surface area = 150 - 180cm2

• Low volume but very large SA which is highly vascularised and a thin barrier to cross for drug delivery.
• Thin epithelial barrier - quick absorption
• Avoids first pass metabolism - high bioavailability (low doses used)

Question 3

What are the turbinates in the nasal cavity and their role?

Answer 3

• Turbinates are bony structures inside the nose, covered by soft tissue (mucosa) - highly vascularised (plenty of blood flow)
• They regulate airflow and warm and humidify the air you inhale. They do this by swelling up with increased blood flow.
• 3 turbinates present in nose

Question 4

What are the sinuses and their role?

Answer 4

• 4 paired cavities (spaces) in the head with narrow passages connecting them.
• Function: Produce + secrete mucus that drains out of the passages in the nose. This drainage helps keep the nose clean and free of bacteria, allergens and other germs (pathogens).
• Also, humidify the air you breathe before it reaches the lungs.

Question 5

How do the sinuses, turbinates and the septum help to filter the airflow?

Answer 5

• Goblet cells in sinuses secrete mucus
• Mucus = 95% water, 2% mucin, 1% salts, 1% lipids, 1% other proteins (albumin, immunoglobulins, lysozyme, lactoferrin)
• Mucus - drained into the middle turbinate – then coats all the 3 turbinates
• Turbinates + septum - ciliated columnar cells providing mucociliary clearance (trapping + removing pathogens + foreign matter from entering lungs)
• Mucociliary clearance – affected by:
• cigarette smoking
• medicinal products (aspirin, anticholinergics)
• disease states (e.g. cystic fibrosis)
• Warm the cold air to body temperature - humidifying air before air enters lungs - better lung functions

Question 6

Factors affecting absorption of nasal drugs

Answer 6

• Molecular weight
• pH and pKa
• Hydrophilic vs hydrophobic
• Partition co-efficient
• Osmolarity
• Disease state
• Physical/anatomical abnormalities
• Interactions with other drugs

Question 7

What is Rynacrom 4% Nasal Spray used for and how does it work?

Answer 7

• Drug: sodium cromoglicate
• Inhibits degranulation of mast cells - preventing release of histamine + leukotrienes (which cause allergic symptoms + bronchoconstriction) —- aka “mast cell stabiliser”
• Only 7% of total dose administered is systemically absorbed through mucosa - bioavailability of ~1%
• Why?:
• Part of absorbed - excreted unchanged in bile + urine
• unabsorbed dose expelled from nose or swallowed and excreted via GI tract
• Hence takes few days to take effect - should be in regular use during hay fever season

Question 8

What is Otrivine 0.1% Nasal Spray used for and how does it work?

Answer 8

• Drug: xylometazoline
• Sympathomimetic agent - alpha-adrenoceptor activity —> vasoconstriction of nasal blood vessels
• More space made for airway - decongestion of mucosa of the nose + pharynx – easier breathing
• Onset time - few mins + lasts up to 10hrs
• Minimal systemic absorption - for localised drug delivery.

Question 9

What is PecFent 0.1% or 0.4% Nasal Spray used for and how does it work?

Answer 9

• Drug: fentanyl citrate
• Opioid analgesic - interaction with opioid u-receptor
• Used for management of breakthrough pain in adults with cancers
• Formulation design:
• in situ gelling solid nasal formulation where fentanyl diffuses from gel and absorbed through nasal mucosa
• Rapid absorption - much faster than oral mucosa route (Oral Transmucosal Fentanyl of the same dose)
• Disadvantage - clinical effect for 10-20 minutes