Nasal Delivery Challenges

Despite easy access, the geometry of the nose makes the reliable and efficient delivery of drugs to the mucosal surfaces challenging. The nasal valve is the narrowest segment of the respiratory tract, accounting for up to 80 percent of nasal resistance and almost half of total respiratory resistance. Sniffing causes additional narrowing of the elastic tissues of the valve.

Traditional spray pumps deliver the dose primarily to the anterior segment of the nasal passage, which is lined with skin-like lining (or epithelium). Effective, targeted drug delivery requires particles to be delivered beyond the nasal valve to the mucosal surfaces that are lined by a single cell-thick columnar epithelium.

Traditional spray pump technology typically produces a mean particle size (MPS) of approximately 50µm, where the fraction of particles <10µm is approximately five percent. These pumps cannot provide MPS much less than 30µm. A mist with a MPS less than 30-40µm is likely to include a higher fraction of small particles (<10µm) than the five percent recommended by FDA guidelines to reduce the risk of lung inhalation.

The triangular shaped valve area located two to three centimeters into the nose limits the fraction of particles able to penetrate further. The particles leaving a traditional spray pump have a high velocity, causing the larger particles, in particular, to be shot against and deposited anterior to, or in, the nasal valve region. The relatively wide plume angle of the mist leaving the nozzle may also contribute to anterior impingement of particles.

A considerable fraction of the dose deposited in this anterior region may drip out or eventually be wiped away or be blown out of the nose without entering deeper regions. The fraction that is transported toward the posterior seems to be mainly cleared along the floor of the nose, limiting the exposure to the mucosal surface. Additionally, sniffing frequently performed to avoid drip out can suck a large part of the dose through the nose to the mouth, to be lost to swallowing.