(609c) High Efficient Separation of Mono- and Di-Tocopherol Polyethylene Glycol Succinates Using Ionic Liquid Extraction

High efficient separation of mono- and di-tocopherol polyethylene glycol succinates using ionic liquid extraction

Liyun Kong, Qiwei Yang, Huabin Xing, Zongbi Bao, Yiwen Yang*, Qilong Ren

(Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China)

* Corresponding author.  Tel.: +86-571-87952773 Fax: +86-571-87952773

                      E-mail address: ceywyang@zju.edu.cn

Tocopherol polyethylene glycol 1000 succinate (TPGS 1000), which is a water soluble derivative of natural vitamin E, is synthesized by the esterification of tocopherol acid succinate (TAS) with polyethylene glycol (PEG). Due to the equal activity of the two hydroxyl groups in PEG, two types of esters (mono- and di-TPGS) exist in commercial TPGS product. However, when we mention TPGS, we usually refer to mono-TPGS, and the typical characteristics are also on account of mono-TPGS. Being an excellent amphiphilic molecule with HLB number of 13, TPGS can be used as solubilizer, emulsifier, absorption enhancer and as a vehicle for lipid-based drug delivery formulations. Two hydrophobic TAS in the molecule of di-TPGS lead to the lower HLB number and almost insoluble in water, making di-TPGS have different uses.

Recommended methods for the separation of mono- and di-TPGS were chromatographic methods which had low treatment capacity, were solvent consuming, or required large equipment investment, so that they were not economically favorable for large-scale production. Here we proposed an extraction method which has the properties of high capacity, low solvent consumption, small investment. Therefore, it is suitable for continuous and industrial production.

Serious emulsification occurred when using water-ethyl acetate extraction system for the separation of mono- and di-TPGS, resulted from the amphiphilic structure of TPGS. Meanwhile the distribution coefficient of mono-TPGS was as low as 0.012. Addition of sodium chloride could eliminate emulsification, but resulted in no distribution of mono-TPGS in water. Organic solvents such as methanol, ethanol and n-propanol can be used to reduce emulsification too. Extraction results of these solvents didn’t come up to expectation with distribution coefficient of mono-TPGS less than 0.3 at 293 K.

Introduction of ionic liquids (ILs) got excellent result. Efficient demulsification and separation were achieved simultaneously with the ternary biphasic ILs/water-ethyl acetate extraction systems. This might be owing to the special structure and property of ILs which are liquid salts at room temperature, and are composed of asymmetric organic cations and organic or inorganic anions. ILs of [C_nmim][Cl] and [C_nPy][Br] with different alkyl chains (n=2 ~ 12) were investigated. The distribution coefficients of mono- and di-TPGS increased rapidly with the increment of the alkyl chain length in cations. For [C_nPy][Br] at the initial concentration of 5 mol% in water at 303 K, when n=6, 8 and 12, the distribution coefficient of mono-TPGS (D_mono-TPGS) were 1.62, 7.75 and 15.09, coupled with the selectivity (mono-TPGS to di-TPGS) as high as 188.37, 22.79 and 8.53, respectively. D_mono-TPGS in [C_nPy][Br]- water/ethyl acetate extraction systems were hundreds of times higher than D_mono-TPGS in water/ethyl acetate system.

When the initial concentration of ILs ([C₈Py][Br] and [C₁₂Py][Br]) in water varied from 0.4 to 20 mol%, D_mono-TPGS reached a maximum at 4 mol%. Maximum existed in the distribution coefficient with the increase of the initial molar percent of ILs in water revealing the diluent’s swing effect in this extraction process. Inverse extraction-temperature relationship was observed due to the inverse solubility-temperature behavior of the typical nonionic surfactant structure of mono- and di-TPGS. Finally, this method can be successfully expanded to the separation of other mono- and di- polyethylene glycol alkyl esters, such as mono- and di-polyoxyethylene laurates, mono- and di-polyoxyethylene palmitates, mono- and di-polyoxyethylene oleates and mono- and di-polyoxyethylene stearates, etc.