Characterization of minocycline powder micronized by a supercritical antisolvent (SAS) process

The effect of the supercritical antisolvent micronization (SAS) process in the minocycline was evaluated in terms of particles morphology and density of the obtained powder. The minocycline was precipitated in a continuous mode from an ethanol solution using supercritical carbon dioxide as antisolvent and particles with a mean diameter around 250 nm were obtained (at 40 °C; 130 bar; solution concentration of 10 mg mL−1; solution flow rate of 1 mL min−1 and antisolvent flow rate, measured at room temperature and atmospheric pressure, of 6.56 L min−1). Moreover, the Scanning Electron Microscopy (SEM) and the X-ray Diffraction (XRD) allowed the comparison between the crystalline initial state and the amorphous particles obtained after the supercritical micronization process.The density of the minocycline was determined by gas picnometry, before and after the micronization process, and the obtained results showed that it passes from an initial density of 1.574 to 2.951 g cm−3 after the processing. The increase in density of the micronized powder is clearly in contrast with the idea that SAS micronization produces a powder lighter than the starting material. A discussion about the stability and solubility of the precipitated powder, also contributes to highlight the potential of this micronization technique to integrate the pharmaceutical processing and to develop new formulations of this biopharmaceutical.