Formation and stabilization of ibuprofen nanoparticles by pulsed rapid expansion of supercritical solutions

Pulsed rapid expansion of supercritical solutions (RESS) was used to micronize racemic ibuprofen and S-ibuprofen. The characterization of the particles was carried out with rapid-scan infrared spectroscopy in situ, 3-wavelengths-extinction measurements, a scanning mobility particle sizer, scanning electron microscopy, and X-ray diffraction. We observed the formation of nanosized primary particles that coagulate and agglomerate strongly to form large chains of many microns in size. It is investigated where the coagulation/agglomeration processes take place and we demonstrate that it is possible to avoid these processes by forming mixed ibuprofen/polymer particles. The stabilization of separate particles depends strongly on the amount of polymer in the particles. Our specially designed RESS apparatus with two different extractor units allows us to vary the fraction of polymer systematically.