Pharmaceutical dry powder aerosols: Correlation of powder properties with dose delivery and implications for pharmacodynamic effect

Purpose. Efficient dispersion of bulk solids is critical for dry powder aer osol production which can be viewed as a sequence of events from stationary through dilated, flowing and finally dispersed particulates. The purpose o f this study was to test the hypothesis that numerical descriptors of powde r flow properties predict aerosol dispersion and pharmacodynamic effect. Methods. Drug and excipient particles were prepared in size ranges suitable for inhalation drug delivery, and their physico-chemical properties were e valuated. Novel techniques (chaos analysis of dynamic angle of repose and i mpact force separation) were developed and utilized to measure and characte rize powder flow and particle detachment from solid surfaces, respectively. Dry powder aerosol dispersion was evaluated using inertial impaction. Phar macodynamic evaluations of bronchodilation were performed in guinea pigs, f or selected formulations. Results. We observed a direct correlation of powder flow with ease of parti cle separation (r(2) = 0.9912) and aerosol dispersion (r(2) = 0.9741). In v ivo evaluations indicated that formulations exhibiting a higher in vitro do se delivery resulted in a greater reduction in pulmonary inflation pressure . Conclusions. These results integrate powder behavior at various levels and indicate that numerical descriptors of powder flow accurately predict dry p owder aerosol dispersion. A proportionality between aerosol dispersion and pharmacodynamic effect was observed in preliminary in vivo evaluations, whi ch demonstrates the potential of these techniques for correlation studies b etween in vitro powder properties and in vivo effect.