Aerosol dispersion of respirable particles in narrow size distributions using drug-alone and lactose-blend formulations.
OBJECTIVE
To examine the effect of formulation type on the aerosolization of respirable particles in narrow size distributions.


METHODS
Aerosol dispersion of two formulation types (drug alone and 2% w/w drug-lactose blends) containing micronized or spray-dried fluticasone propionate (FP) particles (d50% = 1.3 to 9.6 microm, GSD = 1.8 to 2.2) were examined using cascade impaction at 60 l/min with low and high resistance inhaler devices: Rotahaler and Inhalator, respectively.


RESULTS
The aerosol dispersion of FP particles was significantly affected by the particle size, particle type, inhaler device, and formulation type. Interactions were observed between all factors. Generally, greater powder entrainment was obtained with smaller d50%. Higher emitted doses were obtained from drug-alone formulations of spray-dried FP particles and lactose blends of micronized FP particles. Greater aerosol dispersion of spray-dried FP particles was obtained using lactose-blend formulations with d50% around 4 microm. Greater aerosol dispersion of micronized FP particles was obtained using formulations of drug alone. Larger d50% produced larger mass median aerodynamic diameters.


CONCLUSIONS
Small changes in the particle size within the 1-10-microm range exerted a major influence on aerosol dispersion of jet-milled and spray-dried FP particles using drug-alone and lactose-blend formulations.
Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Margaret D
MD
Louey
Michiel
M
Van Oort
Anthony J
AJ
Hickey
D000280:Administration, Inhalation; D000336:Aerosols; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D005079:Excipients / Q000737:chemistry*; D000068298:Fluticasone; D007785:Lactose / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D013696:Temperature
D000336:Aerosols; D000730:Androstadienes; D005079:Excipients; D011208:Powders; D000068298:Fluticasone; D007785:Lactose