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

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. 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 models were assessed. 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%. 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.