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, TLDin vitro, and APSDTLDin vitro, 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 TLDin vitroand APSDTLDin vitrofor 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 TLDin vitrofrom 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, APSDTLDin vitroprofiles and mass median aerodynamic diameters at the MT exit (MMADTLDin vitro) were determined as functions of MT geometric size across Newman's IPs. The range of mean values (n ≥ 5) for TLDin vitroand MMADTLDin vitrofor 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 TLDin vitroand APSDTLDin vitrofor 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 TLDin vitroand APSDTLDin vitromay be studied using the general method described in this study.
1 Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia.
Xiangyin
X
Wei
1 Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia.
Michael
M
Hindle
2 Food and Drug Administration , Rockville, Maryland.
Renishkumar R
RR
Delvadia
1 Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University , Richmond, Virginia.
Peter R
PR
Byron
D000280:Administration, Inhalation; D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008953:Models, Anatomic; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D015203:Reproducibility of Results; D014018:Tissue Distribution; D014132:Trachea / Q000378:metabolism*
D000336:Aerosols; D001993:Bronchodilator Agents; D019819:Budesonide
Budelin Novolizer; IVIVC; aerosol particle size; cascade impaction; in vitro–in vivo correlations; lung dose; test methods