In vitro aerosol deposition in the oropharyngeal region for Staccato loxapine.
BACKGROUND
The Staccato system employs a thermal vaporization technology to generate pure drug aerosols with a particle size optimized for alveolar deposition, leading to rapid absorption of the drug into the systemic circulation. Unlike most traditional aerosol-generation techniques, the particle size of the thermally generated aerosols is significantly affected by the airflow rate going through the device. The objective of this study was to determine the effects of flow rate and other operating conditions on predicted oropharyngeal and lung deposition when using the Staccato system.


METHODS
In vitro oropharyngeal deposition was measured at airflow rates of 15-80 L/min through the device. Oropharyngeal deposition was also measured for different inhalation profiles, different ambient temperatures and humidities, and device orientations. Deposition was measured using the Alberta geometry model, which was derived based on information available in the literature, CT scans of patients, and observations of living subjects.


CONCLUSIONS
Deposition in the oropharyngeal geometry was consistently approximately 11% of the emitted dose throughout the entire range of flow rates. Such consistency in deposition was due to the fact that mass median aerodynamic diameter (MMAD) varied inversely as the square root of the flow rate, resulting in an approximately constant value for the inertial deposition parameter. Thus, an increase in flow rate, which would increase the momentum of a fixed particle size and generally lead to higher oropharyngeal deposition, was almost exactly counterbalanced by the accompanying decrease in MMAD. Results also showed that deposition in the oropharyngeal region was unaffected by other potentially relevant factors such as different airflow ramp rates, inhalation time, ambient temperature and relative humidity, and device orientations.
Dinh
Khe V
KV
Alexza Pharmaceuticals, Mountain View, California 94043, USA.
Myers
Dan J
DJ
Noymer
Peter D
PD
Cassella
James V
JV
D000280:Administration, Inhalation; D000336:Aerosols; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003198:Computer Simulation; D006801:Humans; D006813:Humidity; D008152:Loxapine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000033:anatomy & histology / Q000378:metabolism; D010316:Particle Size; D015656:Respiratory Mechanics; D012212:Rheology; D013696:Temperature
D000336:Aerosols; D014150:Antipsychotic Agents; D008152:Loxapine