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

Abstract

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 eight registered formoterol-based dry powder inhalers over the European and North African markets were involved in this study, including the reference drug Foradil. Samples were prepared using a multistage liquid impinger (MsLI) and further analyzed by a validated HPLC-UV method to determine the delivered and the fine particle doses (FPDs). 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 (DD) of assessed drugs varied from 8.33 to 9.69 µg, while the FPD was between 1.86 and 3.35 µg. As expected, this work confirmed that the capsule composition and the barrier properties of the primary packaging can affect the FPD of dry powder for inhalation use.

Conclusions

The FPD 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 FPD can be achieved using HPMC capsules and moisture-impermeable primary packaging.

Keywords:

• Aerodynamic performance
• delivered dose
• dry powder inhaler
• fine particle dose
• formoterol
• HPLC-UV

Transparency

Declaration of funding

This work was supported by the Pharmaceutical Analytical Chemistry Laboratory from the University of Liege.

Declaration of financial/other relationships

No potential conflict of interest was reported by the authors.

The peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

YZ conducted the study from sample preparation to data interpretation, and wrote the manuscript. CH designed experiments and supervised this work. CH and PH contributed to the review of the manuscript. All authors read and approved the final manuscript.

Data availability statement

Upon a reasonable request, the datasets of this study are available from the CONTACT.