Inhalation of tobramycin using simulated cystic fibrosis patient profiles

TOBI^® Podhaler™ is a capsule-based drug-device combination (tobramycin inhalation powder [TIP] 28 mg capsules via unit-dose dry powder T-326 Inhaler [Podhaler™]) developed for treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF). We explored how inspiratory flow profiles and mouth-throat geometries affect drug delivery with the T-326 Inhaler.

Inspiratory flow profiles were recorded from 38 subjects aged 6-71 who had CF and varying degrees of lung function impairment. Ten of the inspiratory flow profiles were simulated in the laboratory using a custom breath simulator to determine delivered dose (DD) from the T-326 Inhaler. In vitro total lung dose (TLD_{in vitro} ) was measured using four anatomical throat models, ranging from a child to a large adult.

Aerosol performance was assessed across a range of inspiratory flow profiles. Mean DD ranged from 88.8% to 97.0% of declared capsule content. TLD_{in vitro} ranged from 54.8% to 72.4% of capsule content between the flow profile/throat options tested, and the mean TLD_{in vitro} across the range of flow profiles and anatomical throats tested was 63 ± 5%.

Our findings indicate that the T-326 Inhaler provides reliable drug delivery at flow rates likely to be achieved by a broad spectrum of patients with CF. Importantly, forceful inhalation was not required to achieve a robust TLD_{in vitro} . Pediatr Pulmonol. 2016;51:1159-1167. © 2016 Wiley Periodicals, Inc.