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Combining API and Carrier Engineering to Enable Downstream Processing and Performance in DPIs

Paudel A, Zellnitz S, Faulhammer E, Pinto JT, Stranzinger S, Loidolt P, Brunsteiner M, Khinast J.

RDD Asia 2018. Volume , 2018: 103-110.

Abstract:

This study demonstrates the importance of combining material design and particle processing with multi-scale modeling to enable downstream processing and improved quality of dry powder inhaler (DPI) products. Diverse case studies on constituent powders in DPIs subject to wet surface processing, spray drying, and jet-milling are presented. Results from some of the model systems suggested that the properties of the engineered carrier generally govern the success of downstream unit processes such as powder blending and capsule filling, whereas the active pharmaceutical ingredient (API) properties play an instrumental role in aerosolization performance.

The capsule filling performance of various inhalable powders was used to develop a predictive statistical model. Critical material attributes (CMAs) of the API and excipients and the critical process parameters (CPPs) were identified and their combined impact on the dosing accuracy were assessed. Simulation of the dosator capsule filling process via the discrete element method (DEM) demonstrated qualitatively the impact of powder properties on the dosed powder. In addition, terahertz monitoring of relative powder bed density and dynamics during capsule filling was shown to correlate to off-line capsule fill weight in a simplified mimic of the dosator capsule filling setup.