(440d) Visualization And Conception Of The Atomized Rapid Injection For Solvent Extraction (Arise) Process For The Production Of Highly Respirable Powders

Supercritical fluid (SCF) processing is a viable alternative to conventional methods during the downstream formulation of active pharmaceutical ingredients (API). By harnessing the highly tunable, versatile and unique properties of SCFs, innovative processes have been used to generate API products with characteristics that surpass traditional benchmarks. The characteristics of APIs obtained from SCF processing are often distinctive and cannot be replicated with conventional processing techniques.

Experience with established SCF processes such as the Aerosol Solvent Extraction process (ASES) and the Gas Antisolvent System (GAS) at research and pilot scales have revealed certain opportunities for operational improvement. Processing improvements and the implementation of a novel method of solution coalescence have inspired the conception of the Atomized Rapid Injection for Solvent Extraction (ARISE) process.

In the ARISE process, organic solutions containing dissolved APIs are delivered into supercritical carbon dioxide as a single bolus injection under quasi-isothermal and isochoric conditions to effect homogenization and solvent extraction. With the energized rapid release of organic solutions into the anti-solvent environment, the ARISE process eliminates the use of capillary nozzles and low solution flowrates for atomization, thereby reducing processing times significantly. By effecting precipitation over a larger volume, the ARISE process is also capable of processing with increased nucleation homogeneity, decreased nucleation densities and hence, decreased bulk densities.

The feasibility and tunability of the ARISE process was successfully demonstrated with the generation of dry powders of pharmaceutical actives. At different operating conditions of the ARISE process, dry powders generated was either of very narrow particle size distributions or of extremely low bulk densities. In-vitro analyses of low bulk density products indicated excellent aerodynamic properties and dry dispersibility.