Complex Carrier Particles for Inhalation

The interactive powder mixture is the most widely used approach for dry powder formulations in pulmonary drug delivery, combining micronised drug with a coarse excipient, typically lactose. The excipient improves flowability and aerosolisation, while fine drug particles adhere to its surface and must detach during inhalation to reach the lungs. Detachment is influenced by particle collisions, shear, and drag forces. Despite extensive research, the mechanisms governing drug detachment are not fully understood, as delivery depends on the interplay of drug, carrier, and inhaler device. Carrier particle geometry is particularly critical, yet its effects are difficult to isolate.

This thesis investigates how carrier geometry affects drug loading and detachment using computational modelling, additive manufacturing, and experimental testing. Simplified geometries were first used to isolate surface effects, while in-silico collision models and 3D-printed particles allowed detailed analysis of detachment dynamics. A broader set of complex geometries was then systematically evaluated, revealing significant differences in performance. One geometry, the “Pharmacone”, consistently showed superior drug detachment, attributed to its spiked surface influencing particle movement and airflow interactions.

Experimental studies with 3D-printed carriers confirmed the simulations, showing that geometry strongly affects powder homogeneity and aerodynamic performance. Bayesian optimisation further explored design modifications, identifying improved geometries and clarifying how specific features influence detachment. Overall, the results demonstrate that carrier geometry significantly impacts drug delivery efficiency and highlight how advanced design and modelling approaches can guide optimisation of pulmonary formulations, offering new opportunities to enhance therapeutic outcomes.

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