Automating nasal spray analysis

Nasal sprays and aerosols are becoming increasingly popular methods for drug delivery. The nasal route is a non-invasive way of administering drugs with rapid uptake into the bloodstream and is considered to be important for the systematic delivery of proteins and other macromolecules. A key parameter in defining the efficiency of nasal aerosol delivery systems is the particle size distribution of the aerosol cloud, as this is a predictor of the deposition site for the drug within the nasal passages. To increase nasal deposition and minimise deposition in the lungs and gastro-intestinal tract, aerosol droplets should generally have a mass median aerodynamic diameter greater than 10 to 20 microns. Below this range reduced naso-pharyngeal deposition and increased pulmonary deposition occurs. Droplet size distribution measurements are thus critical during the development of nasal drug delivery systems. The characterisation of nasal sprays and aerosols is now covered by a draft guidance from the US Food and Drug Administration (FDA). This details a series of tests which must be carried out to assess the bioavailability of nasally-delivered drug formulations. These tests include: dose content uniformity; delivery dynamics with respect to particle size; and spray pattern and plume geometry measurements. The FDA has recommended laser diffraction as an accurate and reproducible method for determining droplet size distribution in nasal sprays and aerosols for local action. It has also recommended that automated actuation stations are used for all comparative in vitro bioequivalence tests on nasal sprays in order to decrease result variability associated with manual actuation. This in turn increases the sensitivity for detecting differences between different devices and formulations.