Micronization of levofloxacin by supercritical antisolvent precipitation

Abstract

The process of micronization of levofloxacin (LF, an antibacterial agent of the fluoroquinolone group) by the supercritical antisolvent precipitation technique (SAS) was investigated. It was shown that LF particles of different sizes (from 1 to 10 μm) and of various morphologies (from thin plates to elongated parallelepipeds) can be produced depending on the type of solvent used for conducting micronization. Investigation of the micronized LF preparations using the methods of IR-Fourier spectroscopy, Raman scattering, and circular dichroism showed that the LF micronization caused neither changes in its chemical structure nor racemization. Micronization of LF significantly affects the rate of its dissolution in model systems exhibiting effects dependent on the type of the solvent used for micronization. For example, the highest rate of dissolution at pH 4 was observed for LF preparations micronized with the help of chlorohydrocarbons. It was shown that the rate of dissolution of all micronized LF preparations was higher by 15–30% in comparison with the initial LF, which likely was related to the changes in the degree of crystallinity/amorphousness, as well as of morphologies of microparticles formed in the SAS process.