Assessment of the realistic performance of a high payload dry powder inhaler for the delivery of biomolecules to the respiratory tract

Antonia Zapata del Baño¹, Reanne Beaird¹, Chloe Szeto¹, Antoine Laut², Jonathan Tournaire², Eride Quarta³, William J Ganley¹, Niall Doherty¹, Robert Price¹, Jagdeep Shur¹ & Irene Rossi¹

¹Nanopharm Ltd, An Aptar Pharma Company, Franklin House, Grange Rd, Cwmbran NP44 3WY, United Kingdom

²Aptar Pharma, Route des Falaises, Le Vaudreuil 27100, France,

³University of Parma, Food and Drug Department, Parco Area delle Scienze 27/A, Parma 43123, Italy

Summary

Orbital^™ is a unit dose dry powder inhaler (DPI) capable of delivering high doses to the lungs over several inhalations. The assessment of the realistic performance of Orbital^™ as potential device platform for the delivery of high payload of biomolecules was performed. Most biological drugs are currently administered intravenously. Therefore, the delivery of these formulations to the lungs consist of a promising alternative with an enormous potential to treat several diseases, such as, diabetes, cystic fibrosis or asthma. A spray dried formulation comprising lysozyme was successfully manufactured and the lysozyme showed to be still active after the spray dried process. Even though Orbital^™ device showed a lower emitted fraction, it was more efficient in delivering a higher dose to the lungs with a FPF of 68.57% in comparison to the 52.21% reported by RS01. Predicted regional deposition of the cumulative doses of lysozyme delivered by Orbital^™ showed high deposition to the deep lung (alveolar interstitial region) with lower extra-thoracic fraction compared to RS01, demonstrating the higher de-agglomeration efficiency of Orbital^™. The lung dose achieved in a single breath with Orbital^™ already exceeds that of the RS01. The distribution of the lung dose across three consecutive breaths though Orbital^™ (and RS01) showed the expected pattern of alveolar > tracheobronchial > bronchiolar, with the Orbital^™ achieving nearly 50% alveolar dose on the second and third breaths. This device is able to deliver high doses and it is versatile enough to allow further optimization, particularly focused on improving drug emitted maintaining high respirability.

Key Message

The realist performance of Orbital^™ as potential device platform for the delivery of high payload of biomolecules was assessed. A dry powder with active lysozyme was manufactured. Although Orbital^™ showed a lower emitted fraction, it was more efficient in delivering a higher dose the deep lungs (alveolar interstitial region) compared to RS01.