Micronization of Levofloxacin Hemihydrate Using Supercritical Trifluoromethane

Abstract

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.