AnIn VivoandIn VitroComparison of Two Powder Inhalers following Storage at Hot/Humid Conditions

Abstract

Dry powder inhalers (DPIs) are increasingly being used for the treatment of asthma and COPD. A potential drawback is that DPIs can be sensitive to humidity. Two DPIs, Symbicort Turbuhaler and Seretide Diskus, were stored 3 months at either 25°C/30% RH or 40°C/75% RH. After storage, delivered, as well as fine particle dose, FPD, were tested in vitro and lung deposition, of the steroid components, was assessed in vivo. After storage at 40°C/75% RH, delivered dose as well as FPD from Symbicort Turbuhaler was virtually unchanged while FPD for Seretide Diskus decreased by about 50% despite no decrease in delivered dose. For both products, no difference in FPD was seen after storage at 25°C/30% RH. These in vitro findings were confirmed in the in vivo part of the study. Lung deposition for Symbicort Turbuhaler was unaffected by 40°C/75% RH storage, while for Seretide Diskus it was reduced with about 50%. The study extends previous in vitro observations of impaired performance of Seretide Diskus and demonstrates that this translates into decreased drug delivery to the site of action. The clinical importance of this finding has not been studied but could result in undertreatment.