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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front Chem Sci Eng    2013, Vol. 7 Issue (1) : 72-78    https://doi.org/10.1007/s11705-013-1305-x
RESEARCH ARTICLE
Purification of artemisinin from quercetin by anti-solvent crystallization
Chandrakant R. MALWADE, Haiyan QU(), Ben-Guang RONG, Lars P. CHRISTENSEN
Institute of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Niels Bohrs Allé 1, DK-5230, Odense M, Denmark
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Abstract

In the present work, anti-solvent crystallization of artemisinin from four different organic solvents (methanol, ethanol, acetonitrile, and acetone) was studied. Water was used as anti-solvent. The effect of an impurity (quercetin) on the performance of anti-solvent crystallization of artemisinin was investigated. The fundamental process data such as solubility of artemisinin in pure organic solvents and their binary mixtures with varying composition water were measured at room temperature. The solubility of quercetin was measured only in pure organic solvents at room temperature. Anti-solvent crystallization experiments were designed based on the fundamental process data determined. Firstly, the anti-solvent crystallization of artemisinin without impurity was performed from all four organic solvents and then the experiments were repeated with addition of an impurity (quercetin) while keeping all other process parameters constant. Two different concentrations of impurity, i.e., 10% and 50% of its solubility, in the respective organic solvents at room temperature were used. The effect of impurity on performance of anti-solvent crystallization was evaluated by comparing the yield and purity of the artemisinin obtained with those in the absence of impurity. Results of the present work demonstrated that the presence of quercetin in the solution does not affect the final yield of artemisinin from the solution of each of four organic solvents used. However, the purity of artemisinin crystals were reduced when quercetin concentration was 50% of its solubility in all solvents studied.

Keywords anti-solvent crystallization      artemisinin      quercetin      solubility      Artemisia annua     
Corresponding Author(s): QU Haiyan,Email:haq@kbm.sdu.dk   
Issue Date: 05 March 2013
 Cite this article:   
Haiyan QU,Ben-Guang RONG,Lars P. CHRISTENSEN, et al. Purification of artemisinin from quercetin by anti-solvent crystallization[J]. Front Chem Sci Eng, 2013, 7(1): 72-78.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-013-1305-x
https://academic.hep.com.cn/fcse/EN/Y2013/V7/I1/72
Fig.1  HPLC chromatograms of standard artemisinin and quercetin obtained by using the described method
Fig.1  HPLC chromatograms of standard artemisinin and quercetin obtained by using the described method
Solvent composition /vol-%Solubility /(mg?mL–1)
MethanolAcetoneAcetonitrileEthanol
10037175.6206.524.9
9022.1112187.818
8011.660133.612
70630673.7
604.21236.42.5
501.14170.9
40116.4<0.1
30<0.1<0.11.9<0.1
20<0.1<0.1<0.1<0.1
10<0.1<0.1<0.1<0.1
Tab.1  Solubility of artemisinin in four different organic solvents and their binary mixtures with water at room temperature
SolventSolubility /(mg?mL–1)
Methanol5
Acetone67
Acetonitrile1
Ethanol13
Tab.2  Solubility of quercetin in organic solvents at room temperature
Sample pointAnti-solvent added /mLYield of artemisinin /wt-%Purity of artemisinin /%
Aa)Bb)Aa)Bb)Aa)Bb)
146.2750.7885.357.9199.1586.37
292.7064.2394.783.3397.8686.23
3130.877.6897.788.7797.8489.78
4183.93232.697.998.6797.6773.45
Tab.3  Yield and purity of artemisinin along with volume of anti-solvent added during anti-solvent crystallization of artemisinin from acetone.
Fig.2  De-supersaturation profiles of artemisinin along with solubility of artemisinin in methanol and methanol-water mixtures
Fig.2  De-supersaturation profiles of artemisinin along with solubility of artemisinin in methanol and methanol-water mixtures
Fig.3  FT-Raman spectra of crystals obtained from anti-solvent crystallization of artemisinin from methanol: 1 quercetin hydrate; 2 artemisinin with quercetin (50% of solubility); 3 artemisinin with quercetin (10% of solubility); 4 artemisinin without quercetin; 5 artemisinin raw material
Fig.3  FT-Raman spectra of crystals obtained from anti-solvent crystallization of artemisinin from methanol: 1 quercetin hydrate; 2 artemisinin with quercetin (50% of solubility); 3 artemisinin with quercetin (10% of solubility); 4 artemisinin without quercetin; 5 artemisinin raw material
Fig.4  XRPD patterns of crystals obtained from anti-solvent crystallization of artemisinin from methnol: 1 quercetin hydrate; 2 artemisinin with quercetin (50% of solubility); 3 artemisinin with quercetin (10% of solubility); 4 artemisinin without impurity; 5 artemisinin triclinic polymorph (QINGHAOSU10); 6 artemisinin orthorhombic polymorph (QINGHAOSU01)
Fig.4  XRPD patterns of crystals obtained from anti-solvent crystallization of artemisinin from methnol: 1 quercetin hydrate; 2 artemisinin with quercetin (50% of solubility); 3 artemisinin with quercetin (10% of solubility); 4 artemisinin without impurity; 5 artemisinin triclinic polymorph (QINGHAOSU10); 6 artemisinin orthorhombic polymorph (QINGHAOSU01)
Fig.5  De-supersaturation profiles of artemisinin and quercetin during anti-solvent crystallization from acetone: (a) quercetin concentration of 10% of its solubility in acetone; (b) quercetin concentration of 50% of its solubility in acetone
Fig.5  De-supersaturation profiles of artemisinin and quercetin during anti-solvent crystallization from acetone: (a) quercetin concentration of 10% of its solubility in acetone; (b) quercetin concentration of 50% of its solubility in acetone
ExperimentSolventQuercertin concentration /(mg?mL–1)Artemisinin product purity /%Artemisinin product yield wt-%
1Methanol092.2497.29
20.5a91.2797.27
32.5b76.1898.33
4Acetone098.9598.92
56.7a92.8198.67
633.5b73.4598.67
7Acetonitrile099.6198.69
80.1a99.2598.27
90.5b90.2598.47
10Ethanol090.9483.99
111.3a91.8987.63
126.5b84.7186.73
Tab.4  Yield and purity of artemisinin crystals obtained in anti-solvent crystallization of artemisinin with and without quercetin from different organic solvents at room temperature
Fig.6  De-supersaturation profiles of artemisinin and quercetin during anti-solvent crystallization from methanol: (a) quercetin concentration of 10% of its solubility in methanol; (b) quercetin concentration of 50% of its solubility in methanol
Fig.6  De-supersaturation profiles of artemisinin and quercetin during anti-solvent crystallization from methanol: (a) quercetin concentration of 10% of its solubility in methanol; (b) quercetin concentration of 50% of its solubility in methanol
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