Preparation of chitosan microparticles with diverse molecular weights using supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer

•A novel supercritical process was used to prepare chitosan microparticles.•Chitosan with different molecular weights was successfully micronized.•Particle size tailoring was possible through modulation of the process parameters.•The main structure of chitosan microparticles remained after SAA-HCM process.

Supercritical fluid assisted atomization introduced by hydrodynamic cavitation mixer (SAA-HCM) was used to prepare chitosan microparticles with the well-defined spherical morphology and the controlled particle size distribution as a promising carrier for drug delivery system. Chitosan with different molecular weights (3 kDa, 50 kDa, 300 kDa) was successfully micronized, in which water was used as the solvent for 3 kDa chitosan, while 1.0% (v/v) acetic acid aqueous solution was used for 50 kDa and 300 kDa chitosan, respectively. The process parameters including operating pressure and temperature in the mixer, mass flow ratio of CO2/solution, precipitator temperature and solution concentration were explored to evaluate their influences on the morphologies and size distributions of precipitated particles. Results showed that particle size tailoring (ranging between 0.2 and 5 μm) could be achieved through modulation of the process parameters. After processing by SAA-HCM, Fourier transform infrared spectroscopy did not indicate significant change in the main structure of chitosan microparticles. Compared with raw materials, a decrease in crystallinity and thermal stability was observed for the SAA-HCM processed chitosan microparticles, as demonstrated by X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry.

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