Model informed development of dry powder inhaler (DPI) formulations and processes
Amrit Paudel1,2, Sarah Zellnitz1, Sumit Arora1, Benedict Benque1, Michael Brunsteiner1, Eva Faulhammer1, Peter Loidolt2, Johannes G. Khinast1,2
1Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, Graz, 8010, Austria
2Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, Graz 8010, Austria
Pulmonary drug delivery is increasingly spanning for diverse local and systemic diseases. Dry powder inhalation (DPI) formulations include predominantly carrier-based as well as high dose carrier free products. Despite a long history, the development of DPI products and processes is still largely empirical. Rational development of stable DPI products with reproducible inhalation performance and therefore the desired therapeutic outcome can be achieved through the application of advanced material and formulation science with physical, chemical, biological and engineering principles. To this end, we present herein some representative case studies within the framework of multidisciplinary hierarchical model-informed approaches towards designing, predicting and controlling engineered inhalable microparticles and processes including in silico in-vitro-in-vivo performance of inhaled medicines. For example, application of molecular dynamics simulation for deriving descriptors relevant for DPI performance (eg. electrostatics, hygroscopicity, wetting etc.) will be shown. As a step further, the utility of macroscopic numerical models such as computational fluid dynamics-discrete element method (CFD-DEM) towards the prediction of drug detachment during aerosolisation as well as during dry powder processing such as feeding, blending, filling etc. will be illustrated. Finally, the use of physiologically based pharmacokinetic modelling (PBPK) to assist a different phase of DPI development will be discussed.