Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium

Abstract

Objectives:

The long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) has recently been approved as a once-daily treatment for COPD. The objectives of this study were to determine the dose delivery characteristics of glycopyrronium and compare them with those of the LAMA tiotropium, both delivered by their respective capsule-based dry-powder inhalers (DPIs).

Research design and methods:

Seven inhalation profiles derived from patients with moderate and severe COPD were reproduced to determine the aerodynamic particle size distribution of glycopyrronium delivered by the Breezhaler device, a low-resistance DPI. Theoretical respiratory tract deposition was estimated using a semi-empirical model for healthy lungs. These results were compared with those of tiotropium delivered by the high-resistance HandiHaler device obtained in a previous study using the same set of inhalation profiles. Study limitations are that fine particle fraction (FPF) and particle size are generated by the inhalers are not a direct measure of lung deposition, and the bronchodilator effect of inhaled drugs does not depend solely upon the percentage of the total dose that reaches the lung.

Results:

The mean FPF (≤4.7 µm) was 42.6% of the nominal dose (which refers to the content of the capsule) for glycopyrronium and 9.8% for tiotropium while the mass median aerodynamic diameter (MMAD) was 2.8 µm and 3.9 µm for glycopyrronium and tiotropium, respectively. The mean estimated intrathoracic drug deposition as a percentage of the mean dose delivered to the Next Generation Impactor was 39% for glycopyrronium and 22% for tiotropium.

Conclusions:

The glycopyrronium capsule-based DPI delivered a higher FPF and greater and more consistent intrathoracic deposition irrespective of age and disease severity compared to the tiotropium capsule-based DPI, suggesting that it may be suitable for use by patients with a wide range of COPD severities.

Keywords::

• COPD
• Dry-powder inhaler
• Glycopyrronium
• Tiotropium

Transparency

Declaration of funding

This study was funded by Novartis Pharma AG, Basel, Switzerland.

Declaration of financial/other relationships

P.C., T.K., E.C. and J.J. are employees of Novartis and declare no competing interests. T.V. has received reimbursement for attending scientific conferences and/or fees for presentations and/or consultations and/or educational programs from Boehringer Ingelheim, Chiesi, Janssen-Cilag, GlaxoSmithKline, Novartis, Teva and Mundipharma.

Acknowledgments

The authors were assisted in the preparation of the manuscript by Roberta Sottocornola, a professional medical writer contracted to CircleScience (Macclesfield, UK) and Mark J. Fedele (Novartis). Writing support was funded by the study sponsor Novartis. The authors thank Inamed GmbH and Co. KG, Gauting, Germany who carried out the in vitro dose delivery study and analyzed the results. The authors also thank Dilraj Singh and Richard Pavkov from Novartis for the generation of the patient inhalation flow profiles.

Notes

*These data were presented at the Drug Delivery to the Lungs conference in Edinburgh, Scotland (5–7 December 2012)

†Breezhaler is a registered trade name of Novartis Pharma AG, Basel

‡HandiHaler is a registered trade name of Boehringer-Ingelheim, Ingelheim, Germany

*Respimat is a registered trade name of Boehringer-Ingelheim, Ingelheim, Germany