Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review

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.

Fig. 1

The complex anatomy of the nasal airways and paranasal sinuses

Fig. 2

Illustration of the breath-powered Bi-Directional™ technology. See text for detailed description

Fig. 3

Cross-sections of a human nose with normal dimensions during soft palate closure with Bi-Directional™ flow assessment using CFD. The airflow is entering the right nostril and exiting the left nostril. The figure illustrates the narrow triangular shape of the nasal valve and the narrow slit-like passage of the nasal airway more posterior

Fig. 4

Gamma camera image information (logarithmic “hot iron” intensity scale) from the nasal cavity is superimposed on the corresponding sagittal MRI section. The images are from the same subject and present deposition 2 min after delivery using (a) a traditional liquid spray, (b) the breath-powered Bi-Directional™ powder device, and (c) the breath-powered Bi-Directional™ liquid spray device incorporating the same spray pump as used in a. The initial deposition following traditional spray was greatest in the lower anterior regions of the nose, whereas deposition with the Bi-Directional™ delivery devices was greatest in the upper posterior regions of the nose. The less broad distribution in b following breath-powered Bi-Directional™ powder device is believed to be due to the slower clearance for powder the first 6–8 min, reflecting the dissolution of the powder into the mucosal layer. a and b have been published previously, and they are reprinted with permission from the publisher [14]