Author ORCID Identifier
Doctor of Philosophy
The overall aim of this research project was to evaluate effects of spray drying parameters and storage conditions on solid-state characteristics and aerosol performance of excipient enhanced growth (EEG) powders and to formulate a stable and highly dispersible tobramycin EEG powder to be delivered to pediatric cystic fibrosis subjects using a novel positive pressure dry powder inhaler.
Micrometer-sized albuterol sulfate EEG powders were produced using a medium-sized nebulizer and optimized spray drying conditions. Using trileucine as the dispersion enhancer improved the aerosol performance but showed increased moisture absorption compared to the L-leucine formulation.
The optimized spray drying conditions were then implemented together with controlling the drying gas water vapor density (11.9 g/m3) and storage conditions (15 %RH) for hygroscopic tobramycin EEG powders. A stable tobramycin EEG powder with 75.7% emitted dose and 71.1% respirable fraction was obtained using L-leucine as the dispersion enhancer. The optimized formulation containing trileucine had a respirable fraction of 96.0% and when aerosolized in a 5-year-old mouth-throat model, the mouth-throat airway losses were negligible (~1 %).
Aerosol performance of spray-dried combination formulations was evaluated by laser diffraction. Results indicated this method could accurately characterize emitted aerosols with reduced testing times compared to cascade impactor methods.
A pharmacokinetic model was developed and validated, dose reductions based on age and body weight were found to be required for the tobramycin EEG formulation in pediatric patients to ensure equivalent systemic exposure compared to the nebulized delivery due to the predicted increased dose to lung for this new formulation-device combination.
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