Micronization of Salbutamol Sulfate by Supercritical Antisolvent Precipitation from Single- and Two-Phase CO2–Methanol Mixtures

We have studied the influence of pressure and the concentration of a substance being micronized in solution on the size and morphology of salbutamol sulfate particles produced via supercritical antisolvent (SAS) precipitation. The results demonstrate that SAS micronization from ingle-phase and two-phase methanol–CO2–salbutamol sulfate systems leads to the formation of amorphous spherical particles and crystalline particles elongated in one direction, respectively. If the process is run in the single-phase system, we observe precipitation of considerably smaller particles in comparison with the two-phase region. Moreover, the size of the particles prepared by the SAS method via micronization from the two-phase and single-phase systems decreases and increases with increasing salbutamol concentration in solution, respectively. The main cause of this distinction is related to the mechanisms of mixing of the antisolvent and solution. In the case of the two-phase system, crystallization occurs in droplets at a considerably larger fraction of the solvent in comparison with the single-phase system and, accordingly, at a lower degree of local supersaturation.