Aerosol dispersion of respirable particles in narrow size distributions produced by jet-milling and spray-drying techniques.

Abstract

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. 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). 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. 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.