Aerosol dispersion of respirable particles in narrow size distributions produced by jet-milling and spray-drying techniques.
OBJECTIVE
To examine the effect of particle size and morphology on aerosol dispersion using jet-milled and spray-dried mannitol particles in narrow size distributions within the respirable range.


METHODS
Particle size and morphology were examined by laser diffraction and scanning electron microscopy, respectively. Aerosol dispersion was examined using a cascade impactor with a preseparator operating at a flow rate of 60 L/min, using two inhaler devices: Rotahaler (low-resistance device) and Inhalator (high-resistance device). Powder flow was examined using static and dynamic methods (Carr's compressibility index and vibrating spatula, respectively).


RESULTS
Narrow size distributions of jet-milled and spray-dried particles were produced (d50% = 1.4 to 10.3 microm, GSD = 1.8 to 2.1, and d50% = 1.6 to 7.5 microm; GSD = 1.5 to 1.9, respectively). All particles were highly crystalline. Differences in particle shape were observed between jet-milled and spray-dried particles. Higher fine particle fraction (FPF) and relative fine particle fraction (FPFrel) (greater aerosol dispersion) and lower geometric standard deviation (GSD) (less variation) were obtained using particles with d50% between 2 and 5 microm. Higher mass median aerodynamic diameter were obtained with larger d50%. Spray-dried particles produced greater aerosol dispersion compared with jet-milled particles. Greater aerosol dispersion was obtained using the Inhalator than the Rotahaler.


CONCLUSIONS
Small changes in the particle size within the 1-10-microm range produced a major impact in the aerosol dispersion of jet-milled and spray-dried particles. Even in these narrow size ranges, aggregation plays an important role in aerosol dispersion.
Louey
Margaret D
MD
Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Van Oort
Michiel
M
Hickey
Anthony J
AJ
D000280:Administration, Inhalation; D000336:Aerosols; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D008353:Mannitol / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods
D000336:Aerosols; D011208:Powders; D008353:Mannitol