The influence of formulation on emission, deaggregation and deposition of dry powders for inhalation

Carrier and drug (“active”) particles containing different fluorescent dyes were studied by performing an experimental and theoretical analysis of the influence of formulation on the performance of dry powders for inhalation. The performance was evaluated based on the emission, deaggregation, and deposition of powders from a Spinhaler® into a model throat connected to a collection filter or an isokinetic sampling system and Andersen cascade impactor. Powders containing recombinant human granulocyte-colony stimulating factor/mannitol (GM) exhibited improved dispersion, more facile deaggregation and increased deposition in the model lung than those containing only mannitol (M). These results appear to be due to smaller interparticulate cohesive forces between GM particles as indirectly evidenced by surface indentations and bulk density measurements. Carrier particles (PEG 8000) improved total powder emission, but in many instances reduced the percent of active powder inhaled compared to formulations consisting of active powder alone. In formulations containing the carrier, deaggregation and deposition of active powders were highly dependent on the properties of the active powder and flow rate. The theoretical analysis of particle aerosolization criteria was limited to aerosolization of dry, uncharged powders. A relationship is derived relating flow rate of aerosolized powder to the smallest size of particle ogglomerate that can be expected to survive the turbulence generated by the inhaler/mouth/throat flow profile.