Drug delivery to the nasal cavity: in vitro and in vivo assessment.

Drugs are given intranasally for both local and systemic applications, and the use of the intranasal route is predicted to rise dramatically in the next 10 years. Nasal drug delivery may be assessed by a variety of means, but high reliance is often placed upon in vitro testing methodology (emitted dose, droplet or particle size distribution, spray pattern, and plume geometry). Spray pattern and plume geometry define the shape of the expanding aerosol cloud, while droplet size determines the likelihood of deposition within the nasal cavity by inertial impaction. Current FDA guidance recommends these methods as a means of documenting bioavailability (BA) and bioequivalence (BE) for topically acting solution formulations, because they can be performed reproducibly and are more discriminating among products. Nasal drug delivery in vivo may be determined by several radionuclide imaging methods: the two-dimensional imaging technique of gamma scintigraphy has been used most widely, but the three-dimensional method of positron emission tomography (PET) is being used increasingly often. In some situations a good in vitro/in vivo correlation (IVIVC) exists; for instance, negligible penetration into the lungs has been demonstrated in the case of nasal pump sprays delivering large droplets, while a clear difference may be shown in intranasal deposition between two aerosols with markedly different size distributions. However, recent studies have shown a poorer IVIVC for two similar nasal pump sprays, where significant differences in in vitro parameters were not reflected in differences in nasal deposition in vivo. It is suggested that radionuclide imaging data may have an important role to play as an adjunct to in vitro testing in BA and BE assessments and may provide a clearer understanding of the changes in in vitro parameters that are important for predicting differences in in vivo performance. Copyright 2004 Begell House, Inc.