The Use of Condensational Growth Methods for Efficient Drug Delivery to the Lungs during Noninvasive Ventilation High Flow Therapy

The objective of this study was to evaluate the delivery of nasally administered aerosols to the lungs during noninvasive ventilation using controlled condensational growth techniques. An optimized mixer, combined with a mesh nebulizer, was used to generate submicrometer aerosol particles using drug alone (albuterol sulfate) and with mannitol or sodium chloride added as hygroscopic excipients. The deposition and growth of these particles were evaluated in an adult nose-mouth-throat (NMT) model using in vitro experimental methods and computational fluid dynamics simulations. Significant improvement in the lung dose (3-4x increase) was observed using excipient enhanced growth (EEG) and enhanced condensational growth (ECG) delivery modes compared to control studies performed with a conventional size aerosol (similar to 5 mu m). This was due to reduced device retention and minimal deposition in the NMT airways. Increased condensational growth of the initially submicrometer particles was observed using the ECG mode and in the presence of hygroscopic excipients. CFD predictions for regional drug deposition and aerosol size increase were in good agreement with the observed experimental results. These controlled condensational growth techniques for the delivery of submicrometer aerosols were found to be highly efficient methods for delivering nasally-administered drugs to the lungs.