Development of a systematic theory of suspension inhalation aerosols. I. A framework to study the effects of aggregation on the aerodynamic behaviour of drug particles

When a suspension of drug particles is nebulized, the number of particles in a droplet depends on its size and on the relative sizes of the particles and the concentration of the suspension. Therefore, the drug particle size distribution after aerosolization is, in general, different from the distribution of the primary particles. The dry drug particles left after the evaporation of the propellant from a droplet form a cluster (aggregate). The average number of particles in such an aggregate and the variance of this number is calculated from the Poisson probability distribution function. Further progress is made under the following simplifying assumptions: (1) both the primary drug particles and the droplets are monodisperse; (2) the primary drug particles and the clusters are spherical; and (3) a particular model of packing of particles into aggregates can be adopted. The cumulative mass distribution of the drug as a function of the number of drug particles/cluster, equivalent volume and aerodynamic diameters are computed for a specific model. The ranges of concentration and ratios of droplet/particle diameters where aggregation is likely to affect significantly the aerodynamic behaviour of the drug, are outlined. The theoretical calculations are in qualitative agreement with the available experimental evidence for currently used therapeutic suspension inhalation aerosols. It is suggested that the treatment presented here may be developed into a predictive tool for formulation of aerosols with desired aerodynamic features.