Local Deposition Sites of Drug Particles in a Human Nasal Cavity

INTRODUCTION ABSTRACT Particle depositional studies from nasal sprays are important for efficient drug delivery. The main influences on deposition involve the nasal cavity geometry and the nasal spray device of which its parameters are controlled by the product design. It is known that larger particle sizes (>>10μm) at a flow rate of 333 ml/s impact in the anterior portion of the nose, leaving a significant portion of the nasal cavity unexposed to the drugs. Studies have found correlations for the spray cone angles and particle sizes with deposition efficiencies. This study extends these ideas to incorporate other parameters such as the insertion angle of the nasal spray and the injected particle velocity to observe its effect on deposition. A numerical method utilizing a particle tracking procedure found that the most important parameter was the particle’s Stokes number which affected all other parameters on the deposition efficiency. Nasal drug delivery is a popular way to treat respiratory ailments such as congestion and allergies. It has become an alternative to oral and injection routes of delivering systemic drugs for a variety of diseases and its advantages have been well documented. Information regarding particle deposition within the nasal cavity can be used for effective design of a nasal sprayer device to deliver drugs to specific targeted sites. Various studies adopting human subjects or nasal cavity replicas have found relationships for particle deposition efficiencies with nasal spray parameters, such as spray cone angle and the particle size distribution produced (Cheng et al. 2001, Suman et al. 1999). However, in-vivo and nasal cavity replica methods limit the scope of studies due to their tendency to be intrusive, time consuming and expensive to implement. Numerical analysis allows a wider range of studies (e.g. repeatability and accuracy of a nasal spray injection released from the same location) that is based on advancements in computational models employing Computational Fluid Dynamics (CFD) techniques (Hörschler et al. 2003). NOMENCLATURE A convective flux i a1, a2, a3 constants for drag coefficient equation Recent studies have measured spray characteristics, such as particle size and spray cone angle (Suman et al. 2002). A nasal spray produces drug particles in the range of 5μm up to 200μm with a mean of 45-65μm and spray cone angles ranging from narrow sprays at 35 CD coefficient of drag D, d diameter d mean diameter F drag forces 0 degrees to wide sprays at 70 D 0 degrees. Newman et al. (1998) found that an increase in spray cone angle from 35 g gravitational acceleration 0 to 60 degrees showed a reduction in size of the deposition area as less of the spray was able to penetrate the narrow nasal valve. Cheng et al. (2001) found that deposition in the anterior region increased with an increase in cone angles. In contrast, Suman et al. (2002) found that there was not a significant difference in deposition patterns with respect to spray cone angles. It is argued that the changes in spray angle is unlikely to alter the distribution of droplets in the nose due to the narrow passageway of the nasal valve, compared with the spray plumes which are ten times greater. Thus the emitted plumes never have the opportunity to freely develop in the nasal cavity as they would in an unconfined space. Re Reynolds number u velocity u particle / gas velocity ratio x Cartesian coordinate system j