Antisolvent precipitation for the preparation of high polymeric procyanidin nanoparticles under ultrasonication and evaluation of their antioxidant activity in vitro.

An improved method of ultrasonic antisolvent precipitation was used to prepare micronized high polymeric procyanidins (HPC). Response surface methodology (Plackett-Burman and Box-Behnken design) was employed to predict the optimal preparation conditions and satisfactory mean particle size. Among seven parameters, three parameters (i.e., ultrasonic irradiation power, ultrasonic-stirring time, and stirring speed) were identified as the most significant variables using Plackett-Burman design; thus, these three parameters were further optimized using Box-Behnken design. The optimal preparation conditions for micronized HPC were obtained as follows: dropping speed of 4 mL/min, HPC solution concentration of 0.3 mg/mL, ratio of antisolvent and solvent of 5 mL/mL, precipitation temperature of 10 °C, ultrasonic-stirring time of 14 min, ultrasonic irradiation power of 620 W, and stirring speed of 760 r/min. A minimum mean particle size of 96 ± 2 nm was achieved under the aforementioned conditions. The obtained micronized HPC was analysed by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric and X-ray powder diffraction patterns. Micronized HPC enjoyed the higher quantity dissolved and exhibited stronger antioxidant activity in compared to the unprocessed HPC. These results demonstrated that the improved method has great potential for the production of micronized particles.