Investigation of potential substandard dry powder inhalers on EU and North African markets – Evaluation of the delivered and fine particle doses

Purpose: Discovery of falsified Symbicort® 320/9 Turbohaler® identified in the UK in 2013 demonstrated that falsified dry powder inhalers were also present in the European market. This work aimed to investigate the current situation of formoterol-containing dry powder inhalers in Europe and North Africa by assessing their aerodynamic performance profile.
Methods: A total of 8 registered formoterol-based dry powder inhalers over the European and North African markets were involved in the current study, including the reference drug Foradil®. Samples were prepared using a multistage liquid impinger and further analyzed by a validated HPLC-UV method to determine the delivered and the fine particle doses. This study also examined the impact of freezing-thawing cycles on sample stability in terms of analytical purpose handling.
Results: No substandard dry powder inhalers were identified among the medicinal products involved in this work. The delivered dose of assessed drugs varied from 8.33 µg to 9.69 µg, while the fine particle dose was between 1.86 µg and 3.35 µg. As expected, the present work confirmed that the capsule composition and the barrier properties of the primary packaging can affect the fine particle dose of dry powder for inhalation use.
Conclusion: The fine particle dose of products C and B was respectively 17.4% and 14.2% superior to Foradil®, products D and H had the closest values compared to the original drug, and product F was 34.5% inferior. Additionally, this work showed that a high fine particle dose can be achieved using HPMC capsules and moisture-impermeable primary packaging.