Effect of processing parameters on the physicochemical and aerodynamic properties of respirable brittle matrix powders

Thin film freezing (TFF) was employed to produce brittle matrix powders, capable of forming into respirable low-density particles upon aerosolization. The objective of this study is to investigate the impact of processing parameters in the TFF process on the physicochemical and aerodynamic properties of the resulting formulations. TFF formulation produced at the higher freezing rate (cryogenic surface temperature: -140 °C) showed greater specific surface area, higher porosity and lower density, compared to the TFF formulation prepared at the intermediate freezing rate (cryogenic surface temperature: -50 °C) and slow freezing rate (slow freezing on the shelf of -40°C). All of these enhanced properties induced by faster freezing rate further contributed to an increased fine particle fraction (FPF) of the obtained formulations. Moreover, an increasing trend of FPF was observed for these TFF powders when the initial solid concentration was reduced, probably due to the enhanced brittleness. The variation of the freezing rate and initial solid loading in the TFF process enabled the production of formulations with tailored physicochemical properties and brittleness, leading to improved aerodynamic performance.