The Preparation Of D-α-Tocopheryl Polyethylene Glycol Succinate

D-α-tocopheryl polyethylene glycol succinate(TPGS) is a water-soluble derivative of vitamin E.It consists of a polar PEG tail and a hydrophobicα-tocopherol head,is a nonionic surfactant and an efficient vitamin E supplement and absorption enhancer.TPGS has been widely applied in food,pharmaceutical and nutritional supplement field.In this paper,the analysis,preparation and separation of d-α-tocopheryl polyethylene glycol succinate was studied,and the characterization of the TPGS esters was also performed.Firstly,we developed the HPLC method to analyze the d-α-tocopheryl polyethylene glycol succinate and d-α-tocopheryl acid succinate(TAS) using C18 silica as the stationary phase.An esterolytic procedure catalyzed by KOH was developed to quantify theα-tocopherol content of the d-α-tocopheryl polyethylene glycol succinate product.A HPLC method was also proposed to determine the mono-and di-TPGS,TAS with a C30 sorbent in TPGS mixture.Then the preparation of d-α-tocopheryl polyethylene glycol succinate was studied.It was formed by esterifying a high purity TAS(＞90%) with PEG 1000. Effects of the reaction conditions were studied.The optimum reaction conditions were as follows:reaction temperature was 120℃,n(PEG)/n(TAS) was3(mol/mol), catalyst amount was 0.7%(wt),nitrogen was bubbled into the reaction mixture and no solvent was used.The conversion of d-α-tocopheryl acid succinate was higher than 92%,the molar relative value of the mono- and di-TPGS was higher than 10.Attempt was made to purify the d-α-tocopheryl polyethylene glycol succinate.A simulated moving bed(SMB) process was used to separate the TPGS mixture.The SMB separation was carried out with C18 silica packed column as the sorbent,an acetonitrile / isopropyl alcohol mixture was used as the elution solvent.Di-TPGS with a high purity(＞99%) was obtained after the SMB purification procedure.The silica gel column chromatography was also applied to separate the mixture.The optimum conditions of silica gel column chromatography were as follows:macropore silica gel (100-200 mesh),a dichloromethane/ethyl acetate/methyl alcohol mixture was used as the solvent with gradient elution;the load of sample concentration in mobile phase was 0.436 g/ml.The purity of obtained mono-TPGS was increased to 100%with a total recovery higher than 94%,which is better than the Eastman TPGS product (mono-TPGS content 90%).The structures and properties of the obtained TPGS products were further studied. The chemical structures were characterized by ~1H NMR and FT-IR spectroscopy,and the results confirmed the occurrences of mono- and di-TPGS.Molecular distribution properties were studied by MALDI-TOF MS spectroscopy.The MALDI-TOF MS results showed the degrees of polymerization of the two esters were 22.2,21.8, respectively and the number-averaged molecular masses were 1551,2045, respectively.The melting temperatures of the TPGS esters were investigated by DSC and the thermal stabilities were determined by TGA,showing the different thermal degeneration courses of mono- and di-TPGS.