Nasal drug delivery

What are the 3 main areas of the nasal cavity, and pros/cons of each?

1. nasal vestibule

   1. keratinized epithelium (skin)

   2. relatively impermeable

2. respiratory region (ciliated mucosa)

   1. good for drug absorption (highly vascularized)

   2. ciliary clearance

3. olfactory region

   1. could provide a direct nose to brain pathway

Nasal absorption profile mimics that of what other dosage form?

Intravenous administration

Advantages of the nasal route

• rapid onset of action (comparable to IV)

• ease of delivery

• improved bioavailability (bypass GI tract + liver)

• suitable for patients with dysphagia, nausea, and vomiting

Concerns/limitations

• rapid removal of the drug from site of absorption

  • mucociliary clearance, swallowing, inhalation, runoff, sneezing

• pathologic conditions - cold, allergies

• variability due to incorrect administration

• bad taste or nasal burning

How can we increase the residence time of drug in the nasal cavity?

• place the product in the respiratory region

• decrease volume and increase viscosity

• reduce swallowing and inhalation

How can we increase the surface area of deposition?

• decrease particle (droplet) size (atomization)

How can we decrease run off?

• decrease or avoid irritating ingredients

Sumatriptan nasal spray

• single dose nasal spray device *do NOT test/prime spray before use

• no preservative

Advantage of nasal gels

increase retention and comfort

Natesto nasal gel

• testosterone gel

• administer 3 times daily

• requires priming before first dose

• lightly massage nostrils after administration

• refrain from blowing nose or sniffing for 1 hour after administration

Gel forming nasal gels can utilize what to form a gel?

• temperature dependent polymer

• pH dependent polymer

• mucoadhesive polymer

Sinuva nasal implant

• corticosteroid eluting implant to treat nasal polyps

• expands in ethmoid sinus and delivers drug to nasal polyps

• sustained release for up to 90 days

Delivery to the brain from the nose (olfactory)

• olfactory receptor neurons go to the olfactory bulb

• direct access to the brain via the olfactory bulb, avoiding the BBB

• small surface area limits clinical application