Development of an Inline Dry Powder Inhaler for Oral or Trans-Nasal Aerosol Administration to Children.

Abstract

Background: Dry powder inhalers (DPIs) offer a number of advantages, such as rapid delivery of high-dose inhaled medications; however, DPI use in children is often avoided due to low lung delivery efficiency and difficulty in operating the device. The objective of this study was to develop a high-efficiency inline DPI for administering aerosol therapy to children with the option of using either an oral or trans-nasal approach. Methods: An inline DPI was developed that consisted of hollow inlet and outlet capillaries, a powder chamber, and a nasal or oral interface. A ventilation bag or compressed air was used to actuate the device and simultaneously provide a full deep inspiration consistent with a 5-year-old child. The powder chamber was partially filled with a model spray-dried excipient enhanced growth powder formulation with a mass of 10 mg. Device aerosolization was characterized with cascade impaction, and aerosol transmissions through oral and nasal in vitro models were assessed. Results: Best device performance was achieved when all actuation air passed through the powder chamber (no bypass flow) resulting in an aerosol mean mass median aerodynamic diameter (MMAD) <1.75 μm and a fine particle fraction (<5 μm) ≥90% based on emitted dose. Actuation with the ventilation bag enabled lung delivery efficiency through the nasal and oral interfaces to a tracheal filter of 60% or greater, based on loaded dose. In both oral and nose-to-lung (N2L) administrations, extrathoracic depositional losses were <10%. Conclusion: In conclusion, this study has proposed and initially developed an efficient inline DPI for delivering spray-dried formulations to children using positive pressure operation. Actuation of the device with positive pressure enabled effective N2L aerosol administration with a DPI, which may be beneficial for subjects who are too young to use a mouthpiece or to simultaneously treat the nasal and lung airways of older children.