Radiolabeling of Inhalers
The RESPIMAT and MDI devices that delivered fenoterol or flunisolide were radiolabeled by the addition of the radionuclide “mTc using methods as previously described. These methods were validated in vitro using a high-precision multistage liquid impinger and demonstrated that the radiolabeling procedure did not alter the particle size distribution of either fenoterol or flunisolide in the RESPIMAT or MDI, and confirmed that “mTc is an accurate marker for the in vivo distribution of fenoterol or flunisolide inhaled from both devices. Each metered dose delivered 10 MBq “mTc in addition to the drug substance. antibiotics online
Prior to administration of the radiolabeled aerosol, subjects practiced with a placebo MDI or placebo RESPIMAT until they could perform the correct inhalation technique. Inhalers were fired by the investigator approximately 1 s after the subject began inhaling, except that for the MDI with Aerochamber, the inhaler was fired approximately 1 s before inhalation commenced. Subjects inhaled slowly (targeted rate, 30 L/min) and deeply, and after inhalation, breath was held for 10 s. The subjects then exhaled through a filter in order to trap any aerosol particles in the expired air. During dosing, a cotton wool plug was taped across the nostrils in order to trap any particles inadvertently exhaled through the nose. Aerosol inhalation was performed with the inhaler connected in series with a respiratory inductance plethysmograph (Respitrace) from which duration of inhalation, inhaled flow rate, inhaled volume, and breath-holding pause could be calculated.
Consistency of dosing is an important feature of any inhaler device. In the present studies, to ensure delivery of the correct dosage, both the RESPIMAT and MDI were primed with 10 shots that were fired to waste before use on each study day. A further priming shot was fired to waste immediately before dosing in each volunteer.