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Device Engineering Insights into TOBI Podhaler: A Development Case Study of High Efficiency Powder Delivery to Cystic Fibrosis Patients

Maltz DS, Paboojian SJ.

RDD Europe 2011. Volume 1, 2011: 55-66.

Abstract:

The Podhaler device (Novartis), also known as the T-326 Inhaler, was evolved significantly from the Turbospin device (PH&T) specifically to address the needs of high-payload delivery of engineered particles, such as TIP tobramycin inhalation powder. Through the utilization of a number of engineering test methodologies and analysis tools such as Design of Experiments and high speed video, the original device was redesigned to enable delivery of a very high lung dose (~50 mg tobramycin) while improving patient safety, robustness, manufacturability and usability. One of the key challenges for the design was to ensure robust and consistent device functionality despite the large amount of powder to be delivered and the associated residual powder remaining in the device. At high relative humidity, moisture plasticizes the amorphous powder, lowering its Tg and leading to viscous flow that impedes the function of close-fitting device components. Among the design solutions realized were: management of surface contacts given powder build-up; tolerance analyses to ensure continuous smooth operation; and optimization of critical dimensions with improved understanding of their effects on capsule rotation and aerosol performance. Evaluation of clinical phase 3 results demonstrate that the safety and efficacy of the dry powder TOBI (Novartis) Podhaler is comparable to the TOBI (tobramycin inhalation solution) product, and that product (capsule + device) performance was robust throughout its intended use. Moreover, there was improved patient satisfaction compared to the nebulized product, based on significantly reduced dosing time and improved convenience; these results support validation of the design changes made prior to the initiation of clinical phase 3 studies. TOBI Podhaler received an approval recommendation by CHMP in September 2010.