Anna Simonsson: From material properties to aerosolisation propensity of adhesive mixtures for inhalation: On consecutive relationships between drug load, blend state and blend performance

Abstract

Pulmonary diseases are traditionally treated via inhaled aerosol delivery. One of the major current categories of inhalation therapy is dry powder inhalers (DPIs), which are powder-based, breath-actuated systems. The powder is often composed of the active drug mixed with carrier particles (usually lactose), generating so-called adhesive mixtures. Despite the long-standing use of dry powder inhalers, the production of mixtures reaching high dose efficiency remains challenging.

As a means of describing the spatial distribution of drug particles with increasing drug load, a blend state model has earlier been developed. The rationale behind this model is to categorise mixtures according to their appearance and mechanical properties. The main goal of this thesis was to improve understanding of the influence of increased drug load on mechanical and aerosolisation properties from an extended point of view. This was achieved by varying both the intrinsic properties of the mixtures and the experimental conditions. 

The appearance and properties of the mixtures were investigated mainly via imaging, powder packing and flowability tests, and impaction studies. The main findings indicated that the blend state model was applicable to all mixtures studied. Changes in the structure of the adhesive layer associated with transitions between blend states appeared to have a subsequent impact on both mechanical and aerosolisation properties for given mixtures, which was investigated via statistical methods. Improving knowledge regarding the impact of intrinsic mixture properties and their link to mixture performance could ideally be helpful in the optimisation of mixtures, allowing them to reach their maximum potential.