Drug Delivery to the Nasal Cavity: In Vitro and In Vivo Assessment

Abstract

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.

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

“…It is generally accepted that once drug molecules are applied to the nasal cavity and deposited on the nasal epithelium, they either act locally, or diffuse through the epithelium into the lamina propria where they are absorbed into the capillaries of the nasal cavity and distribute to the rest of the body through the blood stream (1). In this case, drugs are first absorbed from the nose to the blood before reaching the central nervous system (CNS).…”

A Comparison of the Deposition Patterns of Different Nasal Spray Formulations Using a Nasal Cast

“…Theoretically, deposition in the nasal cavity should be dominated by impaction of droplets (and/or particles) of the nasal spray (Newman et al 2004) which, in turn, should be governed primarily by droplet size and plume geometry. Cheng et al (2001) found that larger droplets and a wider spray angle increased deposition in the anterior region.…”

“…However, the utility of tests such as plume geometry and spray pattern is limited in early product development as the unrestricted laboratory test environment fails to represent the narrow confines of the nasal passage. Accordingly, Newman et al (2004) and Suman et al (2002Suman et al ( , 2006 have argued that differences detected by traditional in vitro measurements did not directly translate into significant differences in in vivo deposition patterns, systemic absorption or biological response. In vitro nasal cast deposition measurements, thus, provide more realistic and representative data on spray behavior in the nasal cavity.…”

“…Nasal casts are invariably oversimplified representations of human anatomy, lacking surface properties and clearance via mucociliary movement. Moreover, in vitro models may underestimate the difficulty of getting the aerosolized spray beyond the nasal valve and front surfaces of the turbinates in human (Newman et al 2004). To date, there is no validated nasal cast model for in vitro deposition, and the model presented here is not intended as a surrogate for in vivo studies.…”

Caracterização físico-química de sistemas coloidais em sprays nasais

“…Atualmente há três aproximações para avaliação da performance: estudos in vitro, exposição sistêmica, e entrega local (NEWMAN; PITCAIRN;DALBY, 2004).…”