Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth

Abstract

The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration.

Efficient Nose-to-Lung Aerosol Delivery with an Inline DPI Requiring Low Actuation Air Volume

“…Airflow is not included through the mouth opening, consistent with a subject breathing nasally. Based on the study of Walenga et al (11), deposition in this nasal model was similar to deposition in other models over a range of surface area to volume ratios for particle diameters of approximately 1.5 μm. The model was built using Accura ClearVue by 3D Systems On Demand Manufacturing.…”

“…In transitioning to other formulations, maintaining a highly dispersible powder will be a key requirement. In previous work, we have demonstrated that highly dispersible EEG formulations can be made with terbutaline sulfate (38) and ciprofloxacin (8,11,39). The development of spray dried EEG surfactant formulations is also in progress (40,41).…”

“…With improved delivery devices and formulations, inline DPIs have been tested using in vitro experiments for application to invasive mechanical ventilation (3,7), non-invasive positive pressure ventilation with a face mask (11), and high flow nasal cannula (HFNC) therapy (12). Considering invasive mechanical ventilation, studies by Tang et al (3) and Feng et al (7) have placed the Osmohaler™ containing high dose mannitol powder in a custom chamber and evaluated delivery to the end of endotracheal tubes.…”

Development of a New Inhaler for High-Efficiency Dispersion of Spray-Dried Powders Using Computational Fluid Dynamics (CFD) Modeling

“…Specifically, considering aerosol delivery simultaneously with LFNC therapy, the steady flow cannula emitted dose was 75% of the capsule loaded dose and, with cyclic inhalation, up to 55% of the loaded dose reached a tracheal filter. In a similar study with a positive pressure DPI, Walenga et al (53) previously demonstrated high efficiency lung delivery of an EEG aerosol through a mask interface during noninvasive positive pressure ventilation.…”

Development of an Inline Dry Powder Inhaler That Requires Low Air Volume

“…I nline dry powder inhalers (DPIs) are actuated by a stream of gas that is passed through the device from an external positive pressure source. (1)(2)(3)(4) These devices are useful for generating and delivering an aerosol to patients that may not be able to use a DPI such as children younger than approximately 5 or 6 years. (5)(6)(7) The positive pressure gas source can be used to assist with deep inspiration and help maintain a breath hold in individuals with compromised lung function.…”