The main goal of this work was to assess if the Supercritical CO2-Assisted Spray Drying (SASD) technology is suitable for the production of inhalable composite particles with enhanced properties and improved in-vitro aerodynamic performance while maintaining a high process throughput and yield when comparing to other standard particle engineering technologies. For that purpose, a systematic QbD approach using the design of experiments (DoE) tool, followed by a statistical analysis to predict the powder fine particle fraction (FPF), were implemented.
An established formulation composition previously investigated and optimized (trehalose/leucine at 80/20% (w/w) solubilized in a water/ethanol 80/20% w/w mixture) was used to produce composite particles with the SASD apparatus, using a full-factorial design to assess the impact of the static mixer pressure (P_sat), inlet drying gas temperature (T_in) and feed flowrate (F_feed) on the powder properties and on the in-vitro aerodynamic performance by a gravimetric Andersen Cascade Impactor (ACI) using a Plastiape RS01 at 60 L/min, 4 kPa.
The powders produced using the SASD apparatus presented yields up to 70% (batch size of 11 grams) while enabling the optimization of the overall throughput, the powder properties and the in-vitro aerodynamic performance. Improved in-vitro aerodynamic performance was driven by the successful manipulation of the powder aerodynamic particle size (aPS), which is mainly dictated by the particle size and density by decreasing the feed flowrate (F_feed) and increasing the inlet drying temperature (T_in), reaching FPFED(<5μm) up to 86%.