Evaluation of in vitro and in vivo flow rate dependency of budesonide/formoterol Easyhaler(®).

BACKGROUND: The Easyhaler(®) (EH) device-metered dry powder inhaler containing budesonide and formoterol is being developed for asthma and chronic obstructive pulmonary disease (COPD). As a part of product optimization, a series of in vitro and in vivo studies on flow rate dependency were carried out.

METHODS: Inspiratory flow parameters via EH and Symbicort(®) Turbuhaler(®) (TH) inhalers were evaluated in 187 patients with asthma and COPD. The 10(th), 50(th), and 90(th) percentile flow rates achieved by patients were utilized to study in vitro flow rate dependency of budesonide/formoterol EH and Symbicort TH. In addition, an exploratory pharmacokinetic study on pulmonary deposition of active substances for budesonide/formoterol EH in healthy volunteers was performed.

RESULTS: Mean inspiratory flow rates through EH were 64 and 56 L/min in asthmatics and COPD patients, and through TH 79 and 72 L/min, respectively. Children with asthma had marginally lower PIF values than the adults. The inspiratory volumes were similar in all groups between the inhalers. Using weighted 10(th), 50(th), and 90(th) percentile flows the in vitro delivered doses (DDs) and fine particle doses (FPDs) for EH were rather independent of flow as 98% of the median flow DDs and 89%-93% of FPDs were delivered already at 10(th) percentile air flow. Using±15% limits, EH and TH had similar flow rate dependency profiles between 10(th) and 90(th) percentile flows. The pharmacokinetic study with budesonide/formoterol EH in healthy subjects (n=16) revealed a trend for a flow-dependent increase in lung deposition for both budesonide and formoterol.

CONCLUSIONS: Comparable in vitro flow rate dependency between budesonide/formoterol EH and Symbicort TH was found using the range of clinically relevant flow rates. The results of the pharmacokinetic study were in accordance with the in vitro results showing only a trend of flow rate-dependant increase in lung deposition of active substances with EH.