Insulin Submicroparticles Produced by Supercritical Fluid-Assisted Atomization Process

摘要

Supercritical fluid-assisted atomization was employed to produce insulin submicroparticles from its ethanol/water solution. The effect of the processing conditions, including insulin concentration, ethanol content and solution flow rate, on the morphology and size of the produced particles, especially on their bioactivity was investigated. Insulin particles generated from the process are generally spherical with average sizes between 0.3 and 1μm under different conditions. The particles morphology and size could be controlled by the process conditions: increasing the concentration of insulin tends to produce particles with uniform morphology;decreasing the flow rate of the protein/ethanol/water solution could narrow the particle size distribution. Fourier transform infrared spectroscopy (FTIR), the Lowry method, high performance liquid chromatography (HPLC), differential thermal analysis and thermogravimetry (DTA-TG) were implemented to investigate the bioactivity and solvent (water and ethanol) residue of the produced insulin particles.Results show that the ethanol content in the solution has a more sensitive effect on the final particles bioactivity than other operating factors, a high content of ethanol has a trend to denature the insulin particles, and the solvent residue in the produced particles after the process is negligible.