Micronization of Levofloxacin Hemihydrate Using Supercritical Trifluoromethane

Micronization of the pharmaceutical substance levofloxacin hemihydrate (LFC) was studied by the RESS method with trifluoromethane (CHF3) as a polar supercritical solvent. Scanning electron microscopy showed that, at a CHF3 temperature of 50°C, particles of micronized LFC have the shape of microgranules of submicron size. At a temperature of 100°C, the particles take the shape of thin (less than 0.1-μm-thick) elongated plates with rounded edges. At this temperature, an increase in the CHF3 pressure from 20 to 35 MPa leads to an increase in the average particle size from 1 to 2 μm, respectively. X-ray powder diffraction analysis of samples obtained at a temperature of 50°C determined the identity of the original and micronized LFC substances, which correspond to the structure of levofloxacin hemihydrate C36H40F2N6O8⋅H2O. An increase in the process temperature to 100°C leads to the formation of one of pseudopolymorphs of levofloxacin—levofloxacin monohydrate C18H20F2N3O4⋅H2O—in the micronized LFC.