PURPOSE: The objective of this study was to investigate the hygroscopic growth of combination drug and excipient submicrometer aerosols for respiratory drug delivery using in vitro experiments and a newly developed computational fluid dynamics (CFD) model. METHODS: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in vitro and with CFD in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways. RESULTS: The in vitro results and CFD predictions both indicated that the initially submicrometer particles increased in mean size to a range of 1.6-2.5 μm for the 50:50 combination of a non-hygroscopic drug (budesonide) and different hygroscopic excipients. CFD results matched the in vitro predictions to within 10% and highlighted gradual and steady size increase of the droplets, which will be effective for minimizing extrathoracic deposition and producing deposition deep within the respiratory tract. CONCLUSIONS: Enhanced excipient growth (EEG) appears to provide an effective technique to increase pharmaceutical aerosol size, and the developed CFD model will provide a powerful design tool for optimizing this technique to produce high efficiency pulmonary delivery.
PURPOSE: The objective of this study was to investigate the hygroscopic growth of combination drug and excipient submicrometer aerosols for respiratory drug delivery using in vitro experiments and a newly developed computational fluid dynamics (CFD) model. METHODS: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in vitro and with CFD in a coiled tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways. RESULTS: The in vitro results and CFD predictions both indicated that the initially submicrometer particles increased in mean size to a range of 1.6-2.5 μm for the 50:50 combination of a non-hygroscopic drug (budesonide) and different hygroscopic excipients. CFD results matched the in vitro predictions to within 10% and highlighted gradual and steady size increase of the droplets, which will be effective for minimizing extrathoracic deposition and producing deposition deep within the respiratory tract. CONCLUSIONS: Enhanced excipient growth (EEG) appears to provide an effective technique to increase pharmaceutical aerosol size, and the developed CFD model will provide a powerful design tool for optimizing this technique to produce high efficiency pulmonary delivery.
Authors: A K Kamada; S J Szefler; R J Martin; H A Boushey; V M Chinchilli; J M Drazen; J E Fish; E Israel; S C Lazarus; R F Lemanske Journal: Am J Respir Crit Care Med Date: 1996-06 Impact factor: 21.405
Authors: Benjamin M Spence; Worth Longest; Xiangyin Wei; Sneha Dhapare; Michael Hindle Journal: J Aerosol Med Pulm Drug Deliv Date: 2019-03-11 Impact factor: 2.849
Authors: Ross L Walenga; P Worth Longest; Anubhav Kaviratna; Michael Hindle Journal: J Aerosol Med Pulm Drug Deliv Date: 2017-01-11 Impact factor: 2.849