Improved lung delivery from a passive dry powder inhaler using an Engineered PulmoSphere powder.

Objective: To assess the pulmonary deposition and pharmacokinetics of an engineered PulmoSphere powder relative to standard micronized drug when delivered from passive dry powder inhalers (DPIs).

Methods: Budesonide PulmoSphere (PSbud) powder was manufactured using an emulsion-based spray-drying process. Eight healthy subjects completed 3 treatments in crossover fashion: 370 microg budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1) (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma budesonide concentrations were measured for 12 h after inhalation.

Results: Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9 (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder delivered at both flow rates from the Eclipse DPI was twice as efficiently deposited as pelletized budesonide delivered at 60 L x min(-1) from the Turbuhaler. Intersubject variability was also dramatically decreased for PSbud relative to THbud.

Conclusions: Delivery of an engineered PulmoSphere formulation is more efficient and reproducible than delivery of micronized drug from passive DPIs.