Abstract

Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at −0 °C. Delivered dose (DD) and fine-particle dose (FPD) were tested in vitro before and after storage. BUD inhalers: Turbuhaler and Novolizer showed only small decreases (<15%) in FPD in 40 °C/75% RH, whereas FPD for Easyhaler decreased by >60% (P=0.01) after 1.5 months of storage. Easyhaler also decreased significantly after 6 months of storage in ambient/75%RH by 25% and 54% for DD and FPD, respectively, whereas only small decreases were seen for Turbuhaler and Novolizer (<15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 °C/75% RH, whereas Easyhaler showed a small decrease. FPD (budesonide) decreased for Turbuhaler, Spiromax and Easyhaler by 18%, 10% and 68% (all significant), respectively, at 40 °C/75% RH. In ambient/75%RH, DD was unchanged for all inhalers, whereas FPD (budesonide) decreased for Spiromax (7%, P=0.02) and Easyhaler (34%, (P<0.01)). There are significant differences in device performance after exposure to humid conditions. A clinically relevant decrease of more than half FPD was seen for one of the inhalers, a decrease that may affect patients’ clinical outcomes. Prescriber and patient knowledge on device attributes are essential to ensure optimal drug delivery to the lungs.

Highlights

  • Fixed or free combinations of inhaled corticosteroids (ICS) and long-acting β2-agonists are medications used in the treatment of asthma and chronic obstructive lung disease (COPD).[1]

  • For inhalers stored at 40 °C/75% relative humidity (RH), there was a small decrease (o15%) in fine-particle dose (FPD) for both the Turbuhaler and Novolizer, whereas the decrease in BUD FPD for Easyhaler was more than 60% after 1.5 months, after which it did not change significantly over time

  • For Novolizer, Delivered dose (DD) decreased by 14% and FPD decreased by 10%

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Summary

Introduction

Fixed or free combinations of inhaled corticosteroids (ICS) and long-acting β2-agonists are medications used in the treatment of asthma and chronic obstructive lung disease (COPD).[1] A number of different devices are used for the actual drug delivery to the lungs—e.g., dry powder inhalers (DPIs) and pressurised metred dose inhalers. DPIs are commonly used in the Nordic countries. The major advantage of DPIs compared with pressurised metred dose inhalers is their general ease of use. An inherent disadvantage is their potential sensitivity to humidity at storage. Protection from the external environment to prevent moisture uptake is necessary,[2] which is why different manufacturers use different humidity protections to prolong shelf life

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