In the School of Pharmacy at Virginia Commonwealth University, part of our research is to establish relationships between in vitro experimental aerosol deposition data in physically realistic mouth throat and airway models and in vivo drug deposition behaviour in patients for inhaled pharmaceutical products. Significant inter- and intra-subject variation in aerosol deposition within the respiratory tract arises due to differences in the shape and size of the mouth, throat, and airway geometry, as well as the inhalation maneuvers used by patients. As such, we have incorporated the ASL 5000™ Breathing Simulator to simulate realistic breathing profiles through realistic mouth-throat and airway models to predict and compare drug deposition in those models in in vivo radiolabeled studies in the clinic for a selection of commercial inhalers.
“This multipurpose state of the art test system may provide a way to predict and improve device performance without the need to conduct large clinical trials, and may be of great interest to clinicians and regulatory authorities to predict aerosol respiratory drug deposition in humans.”
Having the ASL 5000 at our disposal enables us to simulate and reproducibly replay realistic inhalation profiles. In our studies, we have employed the median and extreme breathing profiles that were recorded in a clinical study. We aim to investigate the effect of inspiratory parameters such as peak inspiratory flow rate and total inhaled volume on aerosol drug deposition in greater detail than is possible clinically by using the ASL 5000. From our in vitro experiments, we were able to show that the quantity of aerosol deposited in a realistic mouth throat model using realistic inhalation parameters enables us to predict the typical total lung deposition in trained healthy adults. These studies have also employed the ASL 5000 XL, which was designed by IngMar Medical Ltd. specifically to simulate an inhalation profile with a high inhalation volume of up to 5.15 litres, which was necessary to encompass the total range of volumes required for our study.
Our future studies using the ASL 5000 will quantify the particle size distribution of aerosols following delivery through in vitro airway models by coupling a cascade impactor and aerosol mixing inlet to the ASL 5000 Breathing Simulator. This multipurpose state of the art test system may provide a way to predict and improve device performance without the need to conduct large clinical trials, and may be of great interest to clinicians and regulatory authorities to predict aerosol respiratory drug deposition in humans.
Another ongoing project in our respiratory research group involves development of realistic in vitro nasal models as a characterization tool for nasal delivery devices. The ASL 5000 enabled us to evaluate and manipulate the effect of nasal inhalation on in vitro regional nasal deposition of nasal spray products. Integration of the ASL 5000 with our experimental set-up allows experiments to be performed with realistic breathing profiles during nasal inhalation. Moreover, we are able to synchronize nasal spray automated actuation using the TTL signal from the ASL 5000, to allow simultaneous inhalation and delivery of the nasal spray. As a result of consistency in actuation timing, more reproducible and meaningful results can be obtained. The ASL 5000 has had an invaluable impact on this research into the performance of nasal spray devices.
The work at VCU was performed using two breathing simulators: the ASL 5000 and the ASL 5000 XL. Xiangyin Wei, Khanh Huynh, and Dr. Anubhav Kaviratna developed and performed the in vitro inhaler studies. Mandana Azimi has developed the in vitro nasal testing apparatus.