Supercritical Antisolvent Micronization of Minocycline Hydrochloride

Micronization of minocycline hydrochloride dissolved in ethanol and with supercritical carbon dioxide as antisolvent was successfully performed using a recently built SAS apparatus. Amorphous particles of minocycline ranging from 100 to 1000 nm (depending on the operating conditions) were obtained. The mean particle size and the particle size distribution were determined by Dynamic Light Scattering. Images were obtained by Scanning Electron Microscopy (SEM) to verify the shape and the size of the micronized particles. The quality of the micronized minocycline was analyzed by HPLC. Experiments were carried out in order to study the effects of the pressure (75–130 bar), temperature (3550 oC) and concentration of the liquid solution (1-20 mg.mL). Furthermore, the effect of antisolvent/solvent flow ratio on the mean particle size and particle size distribution of the obtained final product was also analyzed.