Purification of artemisinin from quercetin by anti-solvent crystallization

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.

Key words： anti-solvent crystallization; artemisinin; quercetin; solubility; Artemisia annua

References

1 World Health Organization (WHO). WHO Traditional Medicine Strategy 2002-2005. Geneva, 2002

2 Newman D J, Cragg G M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products, 2012, 75(3): 311-335

PMID

3 Wakdikar S. Global health care challenge: Indian experiences and new prescriptions. Electronic Journal of Biotechnology, 2004, 7(3): 217-223

4 Kunle O F, Egharevba H O, Ahmadu P O. Standardization of herbal medicines—a review. International Journal of Biodiversity and Conservation, 2012, 4(3): 101-112

5 Shan J J, Rodgers K, Lai C T, Sutherland S K. Challenges in natural health product research: The importance of standardization. Proceedings of the Western Pharmacology Society, 2007, 50: 24-30

PMID

6 Sarkar S, Latif Z, Gray A. Natural Products Isolation, 2nd ed. New Jersey: Humana Press, 2006

7 Fidock D A. Drug discovery: Priming the antimalarial pipeline. Nature, 2010, 465(7296): 297-298

PMID

8 Brown G D. The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao). Molecules (Basel, Switzerland), 2010, 15(11): 7603-7698

PMID

9 Qu H, Christensen K B, Fretté X, Tian F, Rantanen J, Christensen L P. Chromatography-crystallization hybrid process for artemisinin purification from Artemisia annua. Chemical Engineering & Technology, 2010, 33(5): 791-796

10 Ferreira J F, Luthria D L, Sasaki T, Heyerick A. Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules (Basel, Switzerland), 2010, 15(5): 3135-3170

PMID

11 Chan L, Yuen H, Takayanagi H, Janadasa S, Peh K. Polymorphism of artemisinin from Artemisia annua. Phytochemistry, 1997, 46: 1209-1214

12 Tung H, McCauley A, Midler M. Crystallization of Organic Compounds: An Industrial Perspective. New Jersey: Wiley, 2009

13 Myerson A S. Handbook of industrial crystallization. 2nd ed. Massachusetts: Butterworth-Heinemann, 2001