Particle Engineering : Novel strategies to enhance the efficiency of Dry Powder Inhaler formulations

Administration of drugs via the respiratory tract lacks efficiency despite the variety of inhalers and formulations available. In the case of dry powder inhaler (DPI) formulations, scientists attribute this lack of efficiency to the variety of properties of the powder particles and the devices. Matching these interdependent properties is complex, making it difficult to determine the effect of any single influencing factor. With the aim of resolving this complexity, this thesis presents novel strategies for the development of DPI formulations.
For the purpose of controlling the properties of individual particles and investigating them isolated from each other, this thesis presents the use of Additive Manufacturing (AM). As a technique that enables the production of customised objects, AM is shown to allow applications at the DPI particle level and at a level between device and formulation. The latter level of application involves the manufacturing of structurally complex objects that are inserted in inhaler devices as free levitating dispersing aids (DAs). 
In addition, this thesis explores manufacturing of tailored microstructures as a novel particle engineering approach. AM is presented as a technical solution for controlling and adjusting particle size, design, and chemical composition, which can be used to decipher the complexities of developing enhanced DPI formulations.
For particle design thinking and engineering processes, this thesis presents the use of Numerical Simulation (NS) as a complementary tool. Applying Discrete Element Method (DEM) modelling allows for simulating the formation and dispersion of drug-carrier agglomerates. Simulating corresponding patterns provides insights into the influence of particle morphology on carrier loading and particle detachment.
In summary, this thesis presents AM and NS as novel strategies to engineer and evaluate particles for use in DPI formulations.

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