Anatomy and Physiology of the Nasal Cavity
The nasal cavity has a surface area of about 150 cm2 and is highly vascularized and permeable, making it an attractive route for drug delivery. It consists of the nostrils, nasal vestibule, and three nasal turbinates on each side that increase the surface area. The nasal mucosa contains goblet cells that secrete mucus, cilia to clear particles, and blood vessels beneath a thin epithelium. This anatomical structure enables direct nose-to-brain transport via the olfactory region and systemic absorption through rapid drug transport across the nasal epithelium and entry into systemic circulation via vascularization.
Advantages of Intranasal Delivery
Intranasal drug delivery offers several advantages over other non-invasive routes:
- Bypasses first-pass metabolism: Intranasal Drug Delivery administered via the nasal route enter systemic circulation via the superior vena cava and avoids first-pass metabolism in the liver, allowing for better bioavailability of oral drugs that undergo extensive first-pass metabolism.
- Non-invasive and patient-friendly: Intranasal delivery is less invasive than other parenteral routes like injections and provides an alternative to oral tablets and capsules for patients who have difficulty swallowing. It is also painless and easy for self-administration.
- Rapid onset of action: Absorption occurs quickly across the nasal mucosa and drugs enter the systemic circulation rapidly, resulting in a faster onset of therapeutic effect compared to oral administration.
- Enhances CNS delivery: The nose-to-brain pathway facilitates direct nose-to-brain transport of certain drugs, enabling treatment of central nervous system disorders with improved brain targeting.
Challenges of Intranasal Delivery
While the nasal route provides clear advantages, it also faces challenges that need to be addressed:
- Limited absorption: The nasal cavity has a limited surface area for absorption and restricting factors like mucociliary clearance and nasal discharge can lower bioavailability. Enhancing permeation/absorption is crucial.
- Irritation and congestion: Intranasal formulations often cause irritation, burning sensation and irritation-induced nasal congestion. This needs to be minimized through the use of isotonic and buffered solutions.
- Limited payload: Due to restricted volume, only relatively small molecule drugs (<600 Da) can be delivered intranasally in appreciable quantities. Large/bioactive molecules require absorption enhancers.
- Rapid clearance: Mucociliary clearance removes most of the administered dose within 30-60 minutes, limiting drug residence time in the nasal cavity. Sustained-release formulations are required.
Overcoming these challenges through formulation strategies can help realize the full potential of intranasal delivery for improved patient outcomes.
Intranasal Formulation Approaches
Various formulation considerations and techniques are employed to optimize intranasal delivery:
- Isotonicity adjusting agents: Agents like glycerol, sodium chloride and trehalose maintain isotonicity to prevent irritation on dilution with nasal fluids.
- Buffering agents: pH adjusting buffers like phosphate, acetate, and citrate prevent irritation from changes in nasal pH after drug administration.
- Absorbance enhancers: Surfactants, cell-penetrating peptides, cyclodextrins, chitosan and fatty acids help opening tight junctions and improving permeation.
- Mucoadhesive polymers: Polymers like chitosan, carbopol, polycarbophil form gels or increase viscosity for prolonged retention and absorption.
- Liposomes and nanoparticles: Encapsulation in lipid or polymer vesicles helps solubilize difficult drugs, protects from enzymes and facilitates transport.
- Sustained-release systems: Delivery from gels, microspheres, emulsions or other depot systems provide prolonged residence and sustained levels.
- Thermosensitive systems: In situ gelling systems administered as liquids but undergo sol-gel transition at nasal temperature for extended delivery.
Strategic use of these formulation tools help address the main challenges to maximize intranasal drug performance.
Commercially Available Intranasal Products
Some of the marketed intranasal drug products utilizing this route across different therapeutic categories include:
- Desmopressin (Minirin): Used for diabetes insipidus, central precocious puberty, primary nocturnal enuresis.
- Sumatriptan (Imitrex): Triptan antimigraine drug for acute treatment of migraines and cluster headaches.
- Oxymetazoline (Afrin): Nasal decongestant spray for temporary relief of nasal congestion due to common cold, hay fever, etc.
- Fluticasone propionate (Flonase): Steroidal anti-inflammatory nasal spray used as maintenance therapy for allergic rhinitis.
- Insulin (Afrezza): Inhaled insulin for treatment of diabetes replacing injection.
- Naloxone (NARCAN): Opioid antagonist nasal spray used for emergency treatment of known or suspected opioid overdose.
This illustrates how intranasal formulations have addressed the challenges and expanded the drug repertoire that can leverage this convenient delivery route.
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About Author:
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc. (https://www.linkedin.com/in/money-singh-590844163)
