The Experiment Research On The Solvent Residue Removal Of Heat Sensitive Drugs Used Low Temperature Subcritical CO₂

Solvent residue is an important factor in the research and development of pharmaceutical production. Conventional solvent residue removal methods such as solvent extraction, freeze drying, evaporation drying, have some shortcomings such as solvent secondary pollution, poor removal effect and high operating temperature, which can’t completely suitable for low temperature heat sensitive drugs. Therefore, it is of great significance to develop a kind of solvent residue removal method suitable for low temperature heat sensitive drugs.The temperature control system and solvent residue removal kettle of the supercritical fluid extraction equipment had been modified in this paper, firstly. And then, the experiment of the solvent residue removal from kinds of drugs had been carried out on the basis of the modified device. And the solvent residual content of drugs was analyzed by the gas chromatography.A device with the low operating temperature of0℃and removing the solvent residue from the heat sensitive drugs using the low temperature subcritical CO2as solvent has been designed in this paper. And solvent residue removal from the two kinds of the low temperature heat sensitive drugs had been processed with the operating parameters of4℃,25MPa and3h. The mass fraction of ethanol, acetone and acetonitrile in one drug had been decreased from0.965%,1.007%and0.157%to0.01%,0.034%and0, respectively. The mass fraction of ethanol and acetone in another had been both decreased from0.176%and0.405%to below the detection limit of gas chromatography. Paper still had carried on the single factor experiments of right-hand ibuprofen for solvent residue removal, to verify the influence of pressure, flow, temperature and time to the solvent residue removal.Above experiment results show that, the modified device is suitable for the solvent residue removal of low temperature heat sensitive drugs, and the method of low temperature subcritical CO2can remove the solvent residue from the low temperature heat sensitive drugs fast and efficiently. This study has great significance for the research and production of a large amount of low temperature heat sensitive drugs.