The Design and Performance of the Exubera^® Pulmonary Insulin Delivery System

Abstract

The Exubera system (Pfizer, New York, NY/Nektar Therapeutics, San Carlos, CA) is an integration of five major new technologies: protein formulation, powder processing, powder filling, drug packaging, and delivery device. The product provides a simple interface, where the patient interacts only with the delivery device and powder packaging. These components were designed together to assure repeatable dosing when used by a wide range of patients under real-world life-style and handling conditions. The device design is purely mechanical, using patient-generated compressed air as the energy source. Upon actuation, a sonic discharge of air through the novel release unit reproducibly extracts, de-agglomerates, and disperses the inhalation powder into a respirable aerosol. A clear holding chamber allows for patient feedback via dose visualization and separates aerosol cloud generation from the inspiratory effort. The Exubera product was tested under a wide range of typical use conditions and potential misuse scenarios and following long-term usage in clinical trials. These comprehensive characterization programs demonstrated robust aerosol and mechanical performance, confirming the design intent of the inhaler. These studies provide assurance of consistent and reliable dose delivery in a real-world use of the product.

In vitro aerosol characterization of Staccato® Loxapine

“…Emitted dose versus ambient relative humidity near room temperature: a comparison between the present work and earlier published results for the Exubera ® inhaler(Harper et al, 2007).…”

“…Fig. 5 shows a comparison of emitted dose collected at different operating humidities for Staccato Loxapine and Exubera ® (data taken from Harper et al, 2007). Over a wide range of humidities, the emitted dose delivered from Staccato Loxapine was more consistent than those from the Exubera DPI.…”

“…Emitted dose can be significantly affected by airflow rate (Boer et al, 1996;Malton et al, 1996;Meakin et al, 1995a,b;Palander et al, 2000;Ross and Schultz, 1996;Tarsin et al, 2004;Zanen et al, 1992), operating humidity and temperature (Jashnani et al, 1995;Jashnani and Byron, 1996;Meakin et al, 1995a,b;Zhu et al, 2008;Harper et al, 2007), and may also be affected by orientation (Meakin et al, 1995b). Relative humidity of the operating environment can also have an effect on aerosol particle size in DPIs and MDIs (Jashnani et al, 1995;Martin and Finlay, 2005).…”

Aerosolized Medications for Gene and Peptide Therapy

“…Exubera was cleared in 2006 for use in adults with both type-1 and type-2 diabetes and became commercially available soon after. 132,133 By early 2007, 2 additional devices and formulations were in phase-3 testing: the AERx insulin diabetes management system (Novo Nordisk, Bagsvaerd, Denmark, and Aradigm, Hayward, Cali- Fig. 8.…”

The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update

“…Nevertheless, the Exubera ® Pulmonary Insulin Delivery System (Pfizer Pharmaceuticals, New York, NY; and Nektar Therapeutics, San Carlos, CA), was approved by the U.S. Food and Drug Administration in 2006 for use in adults with both type 1 and type 2 diabetes and became commercially available soon thereafter [27, 28]. By early 2007, two additional devices and formulations were in Phase III testing.…”