Optimizing the Magnetic Field Mechanism of a Novel Dry Powder Nebulizer for High Dose Delivery    

Daniel Moraga-Espinoza^1,2, Amr Hefnawy³, Tania Bahamondez-Canas^1,2, Matt Reed⁴, Yun Li⁴, Hugh D. C. Smyth³, & Paul Atkins⁴

¹ Escuela de Química y Farmacia, Universidad de Valparaíso, Gran Bretaña 1093, Playa Ancha, Valparaíso, Región de Valparaíso 2340000, Chile

² Centro de Investigación Farmacopea Chilena, Universidad de Valparaíso, Gran Bretaña 1093, Playa Ancha, Valparaíso, Región de Valparaíso 2340000, Chile

³Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 University Ave, Austin TX, 78712, USA

⁴Nob Hill Therapeutics, Albuquerque NM, USA

Summary

The novel DryNeb dry powder nebulizer works based on magnetic responsive elements (MREs) that can rotate and collide with each other in chaotic motion. Movement of the MREs is driven by an external magnet below the dosing chamber of the device that generates a magnetic field causing the MREs to collide and disperse the drug powder during the inhalation manoeuvre. The work reported in this study further explores optimization of delivery device whereby an external single-phase coil was used to generate a magnetic field causing vertical motion of the MREs, promoting additional collisions with the mesh at the top of the drug dosing chamber. The mesh functions to prevent larger agglomerates from exiting the dosing chamber. It was hypothesized that increasing the collisions of the MREs on the mesh can enhance dispersion of the micronized drug and increase delivery efficiency from the device. The study followed a Box-Behnken Design of Experiments (DoE) approach to determine the effect of applied magnetic field frequency of activation and power applied to the coil on drug delivery performance. A third variable, mesh pore size, was also evaluated. Within the bounds of the operating ranges studied, the study was intended to enable prediction of the most effective combination of magnetic field power, field frequency, and mesh size to produce and control delivery of higher Fine Particle Fractions (FPF) from these features of the dry powder nebulizer. Overall, only the mesh pore size had a significant effect on improving the Emitted Dose (ED) and the FPF from the device. The variables related to the single-phase coil did not demonstrate a significant impact on the device delivery performance. However, after completion of the study, issues were identified with the single-phase coil function, which likely explains its limited influence on delivery performance. The elements of the study related to the single-phase coil will be revisited when the coil is fully operational.