Connor Howe1, Mohammad A M Momin2, Dale R Farkas1, Serena Bonasera2, Michael Hindle2, P Worth Longest3,4. 1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA, 23284-3015, USA. 2. Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, VA, 23298-0533, USA. 3. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA, 23284-3015, USA. pwlongest@vcu.edu. 4. Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, VA, 23298-0533, USA. pwlongest@vcu.edu.
Abstract
PURPOSE: In order to improve the delivery of dry powder aerosol formulations to the lungs of infants, this study implemented an infant air-jet platform and explored the effects of different air sources, flow rates, and pulmonary mechanics on aerosolization performance and aerosol delivery through a preterm nose-throat (NT) in vitro model. METHODS: The infant air-jet platform was actuated with a positive-pressure air source that delivered the aerosol and provided a full inhalation breath. Three different air sources were developed to provide highly controllable positive-pressure air actuations (using actuation volumes of ~10 mL for the preterm model). While providing different flow waveform shapes, the three air sources were calibrated to produce the same flow rate magnitude (Q90: 90th percentile of flow rate). Multiple air-jet DPI designs were coupled with the air sources and evaluated with a model spray-dried excipient enhanced growth formulation. RESULTS: Compared to other designs, the D1-Single air-jet DPI provided improved performance with low variability across all three air sources. With the tested D1-Single air-jet and Timer air source, reducing the flow rate from 4 to 1.7 L/min marginally decreased the aerosol size and significantly increased the lung delivery efficiency above 50% of the loaded dose. These results were not impacted by the presence of downstream pulmonary mechanics (resistance and compliance model). CONCLUSIONS: The selected design was capable of providing an estimated >50% lung delivery efficiency of a model spray-dried formulation and was not influenced by the air source, thereby enabling greater flexibility for platform deployment in different environments.
PURPOSE: In order to improve the delivery of dry powder aerosol formulations to the lungs of infants, this study implemented an infant air-jet platform and explored the effects of different air sources, flow rates, and pulmonary mechanics on aerosolization performance and aerosol delivery through a preterm nose-throat (NT) in vitro model. METHODS: The infant air-jet platform was actuated with a positive-pressure air source that delivered the aerosol and provided a full inhalation breath. Three different air sources were developed to provide highly controllable positive-pressure air actuations (using actuation volumes of ~10 mL for the preterm model). While providing different flow waveform shapes, the three air sources were calibrated to produce the same flow rate magnitude (Q90: 90th percentile of flow rate). Multiple air-jet DPI designs were coupled with the air sources and evaluated with a model spray-dried excipient enhanced growth formulation. RESULTS: Compared to other designs, the D1-Single air-jet DPI provided improved performance with low variability across all three air sources. With the tested D1-Single air-jet and Timer air source, reducing the flow rate from 4 to 1.7 L/min marginally decreased the aerosol size and significantly increased the lung delivery efficiency above 50% of the loaded dose. These results were not impacted by the presence of downstream pulmonary mechanics (resistance and compliance model). CONCLUSIONS: The selected design was capable of providing an estimated >50% lung delivery efficiency of a model spray-dried formulation and was not influenced by the air source, thereby enabling greater flexibility for platform deployment in different environments.
Authors: Timothy E Corcoran; Al Saville; Phillip S Adams; Darragh J Johnston; Michael R Czachowski; Yuliya A Domnina; Jiuann-Huey Lin; Daniel J Weiner; Alex S Huber; Joan Sanchez De Toledo; Cecilia W Lo Journal: Pediatr Pulmonol Date: 2019-04-01
Authors: Karl Bass; Mohammad A M Momin; Connor Howe; Ghali Aladwani; Sarah Strickler; Arun V Kolanjiyil; Michael Hindle; Robert M DiBlasi; Worth Longest Journal: AAPS PharmSciTech Date: 2022-04-19 Impact factor: 3.246
Authors: Connor Howe; Mohammad A M Momin; Karl Bass; Ghali Aladwani; Serena Bonasera; Michael Hindle; Philip Worth Longest Journal: J Aerosol Med Pulm Drug Deliv Date: 2022-02-14 Impact factor: 3.440