Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.
Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.
Burnell
Patricia K P
PK
GlaxoSmithKline R&D, Ware, Herts, United Kingdom. patricia.kp.burnell@gsk.com
Asking
Lars
L
Borgström
Lars
L
Nichols
Steve C
SC
Olsson
Bo
B
Prime
David
D
Shrubb
Ian
I
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D036501:Metered Dose Inhalers; D008953:Models, Anatomic; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000033:anatomy & histology*; D010316:Particle Size; D011208:Powders; D012016:Reference Values; D015203:Reproducibility of Results; D019141:Respiratory System Agents / Q000008:administration & dosage* / Q000737:chemistry
D000336:Aerosols; D011208:Powders; D019141:Respiratory System Agents