Summary
The development of realistic airway models to evaluate orally inhaled and nasal products for local administration of drugs to the airways is gaining regulatory acceptance. Recently, the use of mouth-throat models to determine realistic aerodynamic particle size distributions has been included in a draft albuterol metered dose inhaler guidance document by the FDA. As the development and use of realistic in vitro and in silico methods advances, they can play an important role in the evaluation of new drug formulations and devices, especially in challenging patient populations such as infants. Delivery of surfactant aerosols to premature neonates would allow non-invasive administration of a life-saving therapy. Development of a dry powder surfactant aerosol formulation and drug delivery device has been accelerated using a combination of animal and human upper airway models to compare formulations and evaluate device prototypes prior to pre-clinical testing in animals. Small animal airway models used in combination with preterm infant airway models have demonstrated the feasibility of a dry powder surfactant formulation aerosolized using airflow conditions suitable for neonates. Pre-clinical animal studies have shown that the powder aerosol surfactant formulation has a rapid onset of action and delivery can be completed in less than 1 minute. Improved oxygenation and lung compliance were observed at ~1/10 of the dose used for liquid surfactant instillation. The dry powder surfactant product has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation especially in low- and middle-income countries.