Rifampicin microparticles production by supercritical antisolvent precipitation

Semi-continuous supercritical antisolvent (SAS) precipitation has been used to produce Rifampicin micro- and nanoparticles with controlled particle size (PS) and particle size distribution (PSD). SAS experiments were performed using different liquid solvents. The best micronization results have been obtained using dimethyl sulfoxide (DMSO); using this solvent and operating at 40 degrees C, we obtained nanoparticles with mean diameters ranging from 0.4 to 1 microm at a pressure of 120 bar or more, and microparticles with mean diameters ranging from 2.5 to 5 microm at pressures between 90 and 110 bar. The morphology of Rifampicin precipitates was different too. Nanoparticles connected in small aggregates were obtained at pressures higher than 120 bar, whereas, spherical single microparticles were obtained operating at lower pressures. We also investigated the effect of the concentration of Rifampicin in the liquid solution on particles diameter: we observed that, increasing the liquid concentration, the mean PS increased and the PSD enlarged. XRD and HPLC analysis on treated Rifampicin showed that particles are amorphous and no degradation occurred as a consequence of supercritical processing. We attempted an explanation of the different morphologies observed considering the modification of the high pressure vapor-liquid equilibria of the ternary system Rifampicin-DMSO-CO(2) with respect to the behavior of the binary system DMSO-CO(2).