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 supercritical antisolvent (SAS) apparatus. Amorphous particles of minocycline ranging from 0.1 to 1 μm (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 confirm the morphology and the size of the powders before and after the material is processed. The quality of the micronized minocycline was analyzed by HPLC and was compared with that obtained before micronization.Experiments were carried out in order to study the effects of the pressure (75–130 bar), temperature (35–50 °C) and concentration of the liquid solution (1–20 mg mL−1) on the mean particle size and particle size distribution of the final product obtained. The effect of the antisolvent flow/liquid solution flow (AS/L) ratio was also analyzed. Experiments were performed with (AS/L) ratios equal to 5, 15 and 50 on a mass basis.The experimental results clearly indicate that SAS micronization of minocycline hydrochloride with ethanol as solvent and SC-CO2 as antisolvent, above approximately 80 bar (the only region where it occurs), takes place in a homogeneous supercritical phase formed in the precipitator and particle formation results from gas-phase nucleation. This conclusion is consistent with results mentioned in the literature for similar systems.