Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol.
OBJECTIVE
To report performance characteristics and robustness of the Breezhaler device, a new capsule based dry powder inhaler (DPI) with low resistance (0.07 cm H(2)O(½)/L/min) facilitating high inspiratory flow rates. This device was developed to deliver the novel, inhaled once-daily ultra long-acting β(2)-agonist indacaterol, formulated as an inhalation powder in a capsule, and other investigational drugs including NVA237 and QVA149.


METHODS
Peak inspiratory flow rates via the DPI device were determined in patients with chronic obstructive pulmonary disease (COPD) using an Inhalation Profile Recorder. The flow-rate dependency of the in vitro performance (delivered dose and fine particle mass) of indacaterol in the DPI device was examined. Data on patient experience were captured throughout the indacaterol phase III registration program, and the robustness of the device was investigated after mechanical stress.


RESULTS
Twenty-six patients with COPD that ranged from mild to very severe were recruited (aged 49-84 years); 25 patients were able to generate flow rates in excess of 60 L/min via the DPI device. The mean delivered dose of indacaterol (150 and 300 µg) remained within 15% of the target dose, with a consistent fine particle mass at flow rates of 50-100 L/min. In the indacaterol registration program, patients with mild to very severe COPD were able to use the device successfully, with a low device complaint rate (<0.03%) and no device failures from approximately 90,000 devices. In mechanical stress tests, drop testing resulted in, at most, only cosmetic damage, with no effect on the delivered dose.


CONCLUSIONS
The capsule based DPI device is a low resistance device, suitable for use by patients with a wide range of COPD severities, delivering a consistent dose irrespective of disease severity and age. The device provided consistent delivery of indacaterol with no reported device failures in clinical trials.
Pavkov
Richard
R
Novartis Pharmaceutical Corporation, East Hanover, NJ 07936-1080, USA. richard.pavkov@novartis.com
Mueller
Stefan
S
Fiebich
Katrin
K
Singh
Dilraj
D
Stowasser
Frank
F
Pignatelli
Giovanni
G
Walter
Benoît
B
Ziegler
Dominik
D
Dalvi
Mukul
M
Dederichs
Juergen
J
Rietveld
Ilse
I
D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D058995:Dry Powder Inhalers / Q000295:instrumentation* / Q000592:standards*; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010349:Patient Compliance; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D015363:Quinolones / Q000008:administration & dosage*; D012720:Severity of Illness Index
D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; C510790:indacaterol