Towards a better understanding of the role of carrier mechanical properties in dry powders for inhalation

Interactive blends represent the most commercially significant formulation strategy for dry powder inhalation products, yet their aerodynamic performance is governed by a complex interplay of factors. According to scientific consensus, declines in aerosolisation performance during processing (i.e., mixing) have been attributed to increased contact area and partial embedding of the active pharmaceutical ingredient (API) into the carrier surface as a consequence of press-on forces/deformation processes. While such deformation processes have been investigated in general, no study to date has demonstrated a direct correlation supporting these mechanisms as the underlying reason for aerodynamic performance loss. In this work, model carriers with systematically varied material hardness were generated via a solvent-evaporation process in which plasticiser content was varied, enabling direct investigation of substrate-dependent deformation effects while minimising confounding variables. The results confirm the underlying hypothesis: the extent of aerodynamic performance loss is indeed dependent on the mechanical properties of the carrier substrate, meaning there is a substrate dependency, contrary to published literature. Carrier selection in most earlier studies was largely restricted to commercially relevant grades. Importantly, these findings extend beyond aerodynamic behaviour and are broadly generalisable to other routes of administration, such as adhesive mixtures for oral delivery. Beyond that, the study underscores that the aerodynamic performance of an interactive blend should always, but not only, be evaluated as a function of blending time, or more appropriately, blending energy, rather than as an isolated property.