Optimization of supercritical CO2-assisted spray drying technology for the production of inhalable composite particles using quality-by-design principles

Abstract The main goal of this work was to assess if the Supercritical CO2-Assisted Spray Drying (SASD) is a competitive technology for the production of inhalable trehalose and leucine composite particles with advantageous properties and aerodynamic performance while ensuring a high process throughput and yield. For that purpose, a systematic Quality-by-Design approach using the design of experiments tool, followed by a statistical analysis were implemented. A full-factorial design was used to assess the impact of the static mixer pressure, inlet drying gas temperature and feed flowrate on the powder physical properties and in vitro aerodynamic performance. The powders were produced through SASD with yields up to 70%, while enabling the optimization of the overall throughput. Improved in-vitro aerodynamic performance was driven by the successful manipulation of the process parameters, namely by decreasing the feed flowrate and increasing the inlet drying temperature, yielding powders with fine particle fraction values up to 86%.