In Vitro Tests for Aerosol Deposition. V: Using Realistic Testing to Estimate Variations in Aerosol Properties at the Trachea.

Background: The dose and aerodynamic particle size distribution (APSD) of drug aerosols' exiting models of the mouth and throat (MT) during a realistic inhalation profile (IP) may be estimated in vitro and designated Total Lung Dose, TLD, and APSD, respectively. These aerosol characteristics likely define the drug's regional distribution in the lung.

Methods: A general method was evaluated to enable the simultaneous determination of TLD and APSD for budesonide aerosols' exiting small, medium and large VCU-MT models. Following calibration of the modified next generation pharmaceutical impactor (NGI) at 140 L/min, variations in aerosol dose and size exiting MT were determined from Budelin Novolizer across the IPs reported by Newman et al., who assessed drug deposition from this inhaler by scintigraphy.

Results: Values for TLD from the test inhaler determined by the general method were found to be statistically comparable to those using a filter capture method. Using new stage cutoffs determined by calibration of the modified NGI at 140 L/min, APSD profiles and mass median aerodynamic diameters at the MT exit (MMAD) were determined as functions of MT geometric size across Newman's IPs. The range of mean values (n ≥ 5) for TLD and MMAD for this inhaler extended from 6.2 to 103.0 μg (3.1%-51.5% of label claim) and from 1.7 to 3.6 μm, respectively.

Conclusions: The method enables reliable determination of TLD and APSD for aerosols likely to enter the trachea of test subjects in the clinic. By simulating realistic IPs and testing in different MT models, the effects of major variables on TLD and APSD may be studied using the general method described in this study.