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- Title
Near Elimination of In Vitro Predicted Extrathoracic Aerosol Deposition in Children Using a Spray-Dried Antibiotic Formulation and Pediatric Air-Jet DPI.
- Authors
Farkas, Dale; Thomas, Morgan L.; Hassan, Amr; Bonasera, Serena; Hindle, Michael; Longest, Worth
- 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.
- Subjects
ORAL drug administration; AEROSOLS; INTRANASAL administration; ANTIBIOTICS; SPRAY drying; PROTEOGLYCANS
- Publication
Pharmaceutical Research, 2023, Vol 40, Issue 5, p1193
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-022-03316-9