Intranasal Drug Delivery and Anatomy

Intranasal Drug Delivery

• Two main approaches: nasal cavity and lungs (pulmonary)
• Nasal cavity is a promising route for drug administration, suitable for local or systemic use.
• Examples of local delivery: nasal decongestants, glucocorticoids (e.g., Flonase)
• Examples of systemic delivery: Vitamin B12, pain medications

Anatomy and Physiology of the Nose

• Nose functions for olfaction (smelling) and conditioning inspired air.
• Nasal cavity turbinates are important for intranasal drug delivery.

Regions of the Nasal Cavity

• Three regions: vestibular, respiratory, olfactory
• Vestibular Region: filters and baffles air, lined with hairs and pseudostratified epithelium, nasal valve.
• Respiratory Region: consists of three turbinates (inferior, middle, superior), functions in directing, heating, and humidifying air, increasing surface area for aerosol deposition and drug absorption. Inferior turbinate connects with nasal lacrimal ducts, middle with sinuses, and superior with less significance.
• Olfactory Region: located above the respiratory region; thin layer is between the brain and the olfactory region; small surface area.

Nasal Mucosa

• Respiratory Region Epithelium: anterior one-third has various epithelial types (squamous, transitional, pseudostratified columnar), posterior two-thirds are ciliated pseudostratified columnar epithelia with goblet cells producing mucus.
• Mucociliary Clearance: cilia sweep mucus and trapped substances, promoting drug removal, crucial for undissolved drugs. Mucus viscosity affects the clearance rate, significant factor for drug absorption.
• Mucus functions in protection, hydration, trapping airborne materials, and transport.

Blood Supply

• Nasal epithelium is highly vascularized with fenestrated capillaries.
• Drugs can easily enter the bloodstream.
• No hepatic first-pass effect.

Advantages of Intranasal Drug Delivery

• Avoidance of GI acid and enzymatic degradation
• No hepatic first-pass effect.
• Potential for high absorption rates.
• Absorption of large molecules (peptides)
• Immunity to other mucous membranes.

Disadvantages of Intranasal Drug Delivery

• Increased intranasal metabolism.
• Potential complications from pre-existing nasal conditions (e.g., rhinitis, hay fever, asthma, nasal polyps).

Considerations for Product Design

• pH: solutions with pH 4-8 minimize damage to mucociliary apparatus, best maintained around 7-10, buffer capacity is important.
• Osmolarity: isotonic fluids are preferred to minimize irritation in nasal sprays.
• Viscosity: high viscosity can slow mucociliary clearance, increasing residence time, but excessive viscosity hinders drug release, use viscosity-enhancing excipients in suspensions.
• Preservation: antimicrobial preservatives are essential for repeated use products, Benzalkonium chloride is a common preservative but potential toxicity should be considered.

Drug Deposition

• Sprays are primarily deposited in the anterior region of the nasal cavity, while drops provide broader coverage but are cleared more rapidly.
• Sprays are primarily measured dose or single-dose sprays.
• Particle size is critical.

Product Examples (briefly listed here)

• Diazlasine (Afrin): nasal decongestant.
• Corticosteroids: suspensions with surfactants.
• Narcan: single-use.
• Migraine medications: single-dose.
• Nascobal: systemic vitamin B12 deficiency medication, single-day.
• Flumist: single-use vaccine.