Open AccessInitial Development of an Air-Jet Dry Powder Inhaler for Rapid Delivery of Pharmaceutical Aerosols to Infants
Author(s) -
Connor A. Howe,
Michael Hindle,
Serena Bonasera,
Vijaya Krishna Rani,
P. Worth Longest
Publication year - 2021
Publication title -
journal of aerosol medicine and pulmonary drug delivery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 68
eISSN - 1941-2703
pISSN - 1941-2711
DOI - 10.1089/jamp.2020.1604
Subject(s) - aerosolization , nebulizer , aerosol , dry powder inhaler , jet (fluid) , airflow , inhaler , biomedical engineering , medicine , materials science , inhalation , chemistry , anesthesia , aerospace engineering , asthma , mechanical engineering , organic chemistry , engineering
Background: Positive-pressure dry powder inhalers (DPIs) have recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high efficiency aerosolization with low actuation air-volumes (AAVs). The objective of this study was to initially develop the positive-pressure air-jet DPI platform for high efficiency aerosol delivery to newborn infants by using the nose-to-lung route. Methods: Aerosolization performance metrics of six air-jet DPIs were first assessed at AAVs that were consistent with full-term (30 mL) and preterm (10 mL) neonates. Designs of the air-jet DPIs varied based on geometry of the inlet and outlet flow passages and shape of the aerosolization chamber. Aerosolization metrics evaluated at the device outlet were emitted dose (ED) and mass median aerodynamic diameter (MMAD). Designs with the best aerosolization performance were connected to a smoothly expanding nasal interface and full-term infant (3550 g) nose-throat (NT) model with tracheal filter. Results: The three best performing devices had characteristics of a cylindrical and horizontal aerosolization chamber with a flush or protruding outlet orifice. Including multiple air inlets resulted in meeting the aerosolization targets of >80% ED (based on loaded dose) and MMAD <1.8 μm. Reducing the AAV by a factor of threefold from 30 to 10 mL had little effect on aerosol formation. The three leading devices all delivered ∼50% of the loaded dose through a full-term NT in vitro model by using an AAV of 30 mL. Conclusion: With careful selection of design attributes, the air-jet DPI platform is capable of high-efficiency aerosolization of a 10 mg powder mass by using AAVs that are consistent with infant inhalation. The associated infant air-jet DPI system, which forms a seal at the nostril(s) and delivers both the aerosol and a complete inhalation, is capable of rapid and efficient aerosol administration to infant lungs, based on initial testing in a full-term in vitro NT model.