Application of organic nonsolvent in the process of solution-enhanced dispersion by supercritical CO2 to prepare puerarin fine particles

An organic nonsolvent, dichloromethane was employed in the process of solution-enhanced dispersion by supercritical CO2 (SEDS) to prepare fine particles of puerarin. A 23 factorial experiment was designed to investigate and identify the relative significance of the processing parameters on the surface morphology, particle size and particle size distribution of the products. The effect of the nonsolvent/solvent ratio was found to be dominant in the results regarding particle size. Increasing the nonsolvent content of the puerarin solution decreased the particle size significantly. After optimization, the resulting puerarin nanoparticles exhibited a good spherical shape, a smooth surface and a narrow particle size distribution, with a mean particle size of 0.19 μm. After SEDS processing, the measurements of high performance liquid chromatography (HPLC), ultraviolet (UV) and mass spectrometry (MS) indicated there was no change in the chemical composition of puerarin particles; Fourier transform infrared (FTIR) spectroscopy measurement found the minor structural changes occurred on a molecular level; X-ray powder diffraction (XRPD) analysis revealed that the physical state of puerarin shifted into an amorphous form; and a significant increase in the dissolution rate of puerarin nanoparticles was observed. The SEDS process combined with the addition of dichloromethane could produce puerarin nanoparticles without contamination.