Dale Farkas1, Morgan L Thomas1, Amr Hassan2, Serena Bonasera2, Michael Hindle2, Worth Longest3,4. 1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015 , USA. 2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA. 3. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015 , USA. pwlongest@vcu.edu. 4. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA. pwlongest@vcu.edu.
Abstract
PURPOSE: This study evaluated the in vitro aerosol performance of a dry powder antibiotic product that combined a highly dispersible tobramycin powder with a previously optimized pediatric air-jet dry powder inhaler (DPI) across a subject age range of 2-10 years. METHODS: An excipient enhanced growth (EEG) formulation of the antibiotic tobramycin (Tobi) was prepared using a small particle spray drying technique that included mannitol as the hygroscopic excipient and trileucine as the dispersion enhancer. The Tobi-EEG formulation was aerosolized using a positive-pressure pediatric air-jet DPI that included a 3D rod array. Realistic in vitro experiments were conducted in representative airway models consistent with children in the age ranges of 2-3, 5-6 and 9-10 years using oral or nose-to-lung administration, non-humidified or humidified airway conditions, and constant or age-specific air volumes. RESULTS: Across all conditions tested, mouth-throat depositional loss was < 1% and nose-throat depositional loss was < 3% of loaded dose. Lung delivery efficiency was in the range of 77.3-85.1% of loaded dose with minor variations based on subject age (~ 8% absolute difference), oral or nasal administration (< 2%), and delivered air volume (< 2%). Humidified airway conditions had an insignificant impact on extrathoracic depositional loss and significantly increased aerosol size at the exit of a representative lung chamber. CONCLUSIONS: In conclusion, the inhaled antibiotic product nearly eliminated extrathoracic depositional loss, demonstrated high efficiency nose-to-lung antibiotic aerosol delivery in pediatric airway models for the first time, and provided ~ 80% lung delivery efficiency with little variability across subject age and administered air volume.
PURPOSE: This study evaluated the in vitro aerosol performance of a dry powder antibiotic product that combined a highly dispersible tobramycin powder with a previously optimized pediatric air-jet dry powder inhaler (DPI) across a subject age range of 2-10 years. METHODS: An excipient enhanced growth (EEG) formulation of the antibiotic tobramycin (Tobi) was prepared using a small particle spray drying technique that included mannitol as the hygroscopic excipient and trileucine as the dispersion enhancer. The Tobi-EEG formulation was aerosolized using a positive-pressure pediatric air-jet DPI that included a 3D rod array. Realistic in vitro experiments were conducted in representative airway models consistent with children in the age ranges of 2-3, 5-6 and 9-10 years using oral or nose-to-lung administration, non-humidified or humidified airway conditions, and constant or age-specific air volumes. RESULTS: Across all conditions tested, mouth-throat depositional loss was < 1% and nose-throat depositional loss was < 3% of loaded dose. Lung delivery efficiency was in the range of 77.3-85.1% of loaded dose with minor variations based on subject age (~ 8% absolute difference), oral or nasal administration (< 2%), and delivered air volume (< 2%). Humidified airway conditions had an insignificant impact on extrathoracic depositional loss and significantly increased aerosol size at the exit of a representative lung chamber. CONCLUSIONS: In conclusion, the inhaled antibiotic product nearly eliminated extrathoracic depositional loss, demonstrated high efficiency nose-to-lung antibiotic aerosol delivery in pediatric airway models for the first time, and provided ~ 80% lung delivery efficiency with little variability across subject age and administered air volume.
Authors: S G Devadason; M L Everard; C MacEarlan; C Roller; Q A Summers; P Swift; L Borgstrom; P N Le Souëf Journal: Eur Respir J Date: 1997-09 Impact factor: 16.671
Authors: Jeffry G Weers; Yoen-Ju Son; Mark Glusker; Alfred Haynes; Daniel Huang; Nani Kadrichu; John Le; Xue Li; Richard Malcolmson; Danforth P Miller; Thomas E Tarara; Keith Ung; Andy Clark Journal: J Aerosol Med Pulm Drug Deliv Date: 2018-12-06 Impact factor: 2.849
Authors: A H de Boer; P Hagedoorn; M Hoppentocht; F Buttini; F Grasmeijer; H W Frijlink Journal: Expert Opin Drug Deliv Date: 2016-08-30 Impact factor: 6.648
Authors: Anne J Lexmond; Tonnis J Kruizinga; Paul Hagedoorn; Bart L Rottier; Henderik W Frijlink; Anne H de Boer Journal: PLoS One Date: 2014-06-05 Impact factor: 3.240