Abstract
Nasal delivery is the logical choice for topical treatment of local diseases in the nose and paranasal sinuses such as allergic and non-allergic rhinitis and sinusitis. The nose is also considered an attractive route for needle-free vaccination and for systemic drug delivery, especially when rapid absorption and effect are desired. In addition, nasal delivery may help address issues related to poor bioavailability, slow absorption, drug degradation, and adverse events in the gastrointestinal tract and avoids the first-pass metabolism in the liver. However, when considering nasal delivery devices and mechanisms, it is important to keep in mind that the prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines. The narrow nasal valve and the complex convoluted nasal geometry with its dynamic cyclic physiological changes provide efficient filtration and conditioning of the inspired air, enhance olfaction, and optimize gas exchange and fluid retention during exhalation. However, the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored. With this background, the advantages and limitations of existing and emerging nasal delivery devices and dispersion technologies are reviewed with focus on their clinical performance. The role and limitations of the in vitro testing in the FDA guidance for nasal spray pumps and pressurized aerosols (pressurized metered-dose inhalers) with local action are discussed. Moreover, the predictive value and clinical utility of nasal cast studies and computer simulations of nasal airflow and deposition with computer fluid dynamics software are briefly discussed. New and emerging delivery technologies and devices with emphasis on Bi-Directional™ delivery, a novel concept for nasal delivery that can be adapted to a variety of dispersion technologies, are described in more depth.
Highlights
The nose offers easy access to a large mucosal surface well suited for drug- and vaccine delivery
The guidance offers no or limited guidance on nasal products for systemic absorption and for alternative dispensing methods like drops, liquid jets, nebulized aerosol, vapors, and powder formulations. It does not address aspects and challenges related to the nasal anatomy and physiology that are highly relevant for the device performance in the clinical setting like body
Substances absorbed from the anterior regions are more likely to drain via the jugular veins, whereas drugs absorbed from the mucosa beyond the nasal valve are more likely to drain via veins that travel to the sinus cavernous, where the venous blood comes in direct contact with the walls of the carotid artery
Summary
The nose offers easy access to a large mucosal surface well suited for drug- and vaccine delivery. Factors related to the nasal anatomy, physiology and aerodynamics that can severely limit this potential, have historically been challenging to address. The guidance offers no or limited guidance on nasal products for systemic absorption and for alternative dispensing methods like drops, liquid jets, nebulized aerosol, vapors, and powder formulations. It does not address aspects and challenges related to the nasal anatomy and physiology that are highly relevant for the device performance in the clinical setting like body. The aim of this paper is to take a step further by reviewing the characteristics of existing and emerging nasal delivery devices and concepts of aerosol generation from the perspective of achieving the clinical promise of nasal drug and vaccine delivery. Specific attention is given to the particular challenge of targeted delivery of drugs to the upper narrow parts of the complex nasal passages housing the middle meatus where the sinuses openings are located, as well as the regions innervated by the olfactory nerve and branches of the trigeminal nerve considered essential for efficient “nose-to-brain” (N2B) transport
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