Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica.
This paper describes a technique that uses a well-defined human airway replica and gamma counting as a standard method for evaluating and comparing the performance of medical inhalers and spacers. High-fidelity replicas reproduced as needed from master casts made from human cadavers include the oropharyngeal cavity, larynx, trachea, and five to nine generations of bronchi. Deposition in the small airways and alveoli region of the cast is simulated by material that passes through the upstream airways and is collected on foam filters. Deposition patterns in the respiratory tract replica were obtained by using radiolabel in the medical inhaler and by gamma scintigraphy. This technique was used to determine respiratory deposition patterns of salbutamol in a pressurized metered dose inhaler (pMDI) with chlorofluorocarbon (CFC, in-house formulation) and HFA-134 formulations (Proventil hydrofluoroalkane [HFA]). At an inspiration flow of 30 L/min, patterns in the salbutamol/CFC formula showed a high deposition in the oropharyngeal airway (78%) and a 16% deposition in the lung, similar to in vivo measurements reported in the literature. However, the salbutamol/HFA formula showed lower oral deposition (56%) but higher lung deposition (24%). The difference in the oral deposition patterns may be attributed to lower initial spray velocity, initial droplet evaporation rate, and possibly initial droplet sizes of Proventil HFA. The small orifice diameter (0.25 mm) of the Proventil HFA actuator produced a softer plume with a smaller impact force, resulting in lower oropharyngeal deposition. Cascade impactor measurements showed similar aerodynamic particle size distribution of the CFC and HFA formulations. We also showed that using spacers in the Proventil HFA resulted in a lower oropharyngeal deposition and higher lung deposition, indicating beneficial effects. Comparison of oropharyngeal deposition and those predicted by artificial throats used in the impactor measurements showed that, in general, the artificial throat predicted a lower deposition.
Cheng
Y S
YS
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA. ycheng@lrri.org
Fu
C S
CS
Yazzie
D
D
Zhou
Y
Y
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D017402:Chlorofluorocarbons / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000592:standards; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging* / Q000187:drug effects*; D008297:Male; D008953:Models, Anatomic; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000000981:diagnostic imaging* / Q000187:drug effects*; D010316:Particle Size; D011877:Radionuclide Imaging; D013667:Technetium / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D005466:Fluorocarbons
D000336:Aerosols; D000420:Albuterol; D001993:Bronchodilator Agents; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; D013667:Technetium; C094049:apaflurane; D005466:Fluorocarbons