Polysorbate 80 For Injection Free Of Macromolecular Substances

Objective:The main objective was to find the macromolecular substances in polysorbate 80 for injection,compare the solubilizing ability and physical constants between the excepients free of macromolecular substances and the original one,and establish a method to detect the macromolecular substances.Methods:(1)Different portions of polysorbate 80 were obtained by ultra-tubes.The diluted polysorbate 80 was put in to the ultra-tubes,and the portions with substances above 100 KD,10KD~100KD and below 10 KD were collected.The substances in each portion were weighed after freeze drying.(2)The ability of polysorbate 80 to solubilize anisole,huperzine A and tocopherol in water was evaluated.(3)Referring to Chinese Pharmacopoeia(2015 Edition),physical constants of each portion were determined,including viscosity,relative density,absorption spectrum,pH value,infrared spectrum,critical micelle concentration,and micellar particle size.(4)The method of siz-exclusion chromatography was established to determine macromolecular impurities in polysorbate 80.(5)The macromolecular impurities in XNJ injection and their safety were evaluated.Results:(1)Three portions were prepared by ultrafiltrating the diluted polysorbate 80 through different ultra-tubes.After lyophilization,the portion of above 100 KD was 51%,that of 10KD~100KD was 25%,and that below 10 KD was 11%.(2)Polysorbate 80 was able to solubilize anisole,but almost not to solubilize huperzine A in water.The ability of each portion free of macromolecular substance to solubilize tocopherol became stronger than that of the original polysorbate 80.(3)It was found that the physical and chemical properties of the samples were different between the portions free of macromolecular substances and the original excipient.Comprehensive evaluation determined that the physical properties of polysorbate 80 free of macromolecular substances were more stable and were more suitable for injection than the original excipient.(4)Size-exclusion chromatography can be more easily and quickly applied to the detection of macromolecular substances in polysorbate 80 for injection.(5)It was found that XNJ injection free of macromolecular substances was safetier than the original one,suggesting that the safety of XNJ injection was improved by removing the macromolecular impurities.Conclusion:Polysorbate 80 for injection contains a good portion of macromolecular substances and the substances can be removed by ultrafiltration.The solubilizing ability of the portion free of macromolecular substances become stronger,and its safety was improved.