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 degrees C, particles of micronized LFC have the shape of microgranules of submicron size. At a temperature of 100 degrees C, the particles take the shape of thin (less than 0.1-mu m-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 mu m, respectively. X-ray powder diffraction analysis of samples obtained at a temperature of 50 degrees C determined the identity of the original and micronized LFC substances, which correspond to the structure of levofloxacin hemihydrate C36H40F2N6O8 center dot H2O. An increase in the process temperature to 100 degrees C leads to the formation of one of pseudopolymorphs of levofloxacin-levofloxacin monohydrate C18H20F2N3O4 center dot H2O-in the micronized LFC.