In-line characterization of pharma-nanoparticle production with supercritical fluid expansion

Nanoformation of an active pharmaceutical ingredient (API) in controlled expansion of supercritical solution (CESS®) was studied in situ with a schlieren imaging technique in wide range of pre-expansion and expansion conditions, involving pressures up to 1000 bars. The optical methods allowed measurements on solvent state in the first micro and milliseconds of the expansion. Quantitative values on jet shape and solvent thermodynamic state were obtained for different nozzle configurations. These values, combined with mathematical modelling, enabled tracking the nanoparticle formation along the flow. We also report on the importance of solvent phase behavior demonstrated by three fundamentally different expansion schemes: supercritical (SC) to liquid/gas, SC to gas/liquid, and SC to SC. Scanning electron microscope images of the nanosized API are presented. This shows that one can have controlled particle formation by altering the thermodynamic conditions at the nozzle and changing the expansion path. The results guide the in-house process optimization and offer insight into the physics of supercritical fluid processing