TY - JOUR
T1 - Chromatography-crystallization hybrid process for artemisinin purification from artemisia annua
AU - Qu, Haiyan
AU - Christensen, Kathrine Bisgaard
AU - Fretté, Xavier
AU - Tian, Fang
AU - Rantanen, Jukka
AU - Christensen, Lars Porskjær
PY - 2010/5
Y1 - 2010/5
N2 - The feasibility of using a chromatography-crystallization hybrid separation process for isolation and purification of artemisinin from the herbal plant Artemisia annua was studied. After separating the crude extracts of Artemisia annua by flash column chromatography, a two-step antisolvent crystallization process was used for further isolation and purification. The two-step antisolvent crystallization process was designed based on the solubility of artemisinin in different solvents and solvent mixtures. The first step crystallization process was to remove impurities from the solution and the second step to isolate artemisinin. The crystallization behavior of the two polymorphs of artemisinin during the antisolvent crystallization process was also studied by performing crystallization in solutions of artemisinin in acetonitrile and acetone, respectively. It was observed that the formation of the two polymorphs of artemisinin in acetone solution follows the Ostwald's rule of stages. Fast feeding of the antisolvent (water) resulted in crystallization of the metastable triclinic form which then transformed to the stable orthorhombic form through a solvent-mediated transformation mechanism. The stable orthorhombic form crystallized out when water was fed slowly. Crystallization from acetonitrile always yielded the stable orthorhombic form regardless of the feeding rate of the antisolvent. Finally, a chromatography-crystallization hybrid separation process was proposed and tested. The results of the present work demonstrated the feasibility of combining the advantages of column chromatography and crystallization to improve efficiency of the isolation of artemisinin from Artemisia annua.
AB - The feasibility of using a chromatography-crystallization hybrid separation process for isolation and purification of artemisinin from the herbal plant Artemisia annua was studied. After separating the crude extracts of Artemisia annua by flash column chromatography, a two-step antisolvent crystallization process was used for further isolation and purification. The two-step antisolvent crystallization process was designed based on the solubility of artemisinin in different solvents and solvent mixtures. The first step crystallization process was to remove impurities from the solution and the second step to isolate artemisinin. The crystallization behavior of the two polymorphs of artemisinin during the antisolvent crystallization process was also studied by performing crystallization in solutions of artemisinin in acetonitrile and acetone, respectively. It was observed that the formation of the two polymorphs of artemisinin in acetone solution follows the Ostwald's rule of stages. Fast feeding of the antisolvent (water) resulted in crystallization of the metastable triclinic form which then transformed to the stable orthorhombic form through a solvent-mediated transformation mechanism. The stable orthorhombic form crystallized out when water was fed slowly. Crystallization from acetonitrile always yielded the stable orthorhombic form regardless of the feeding rate of the antisolvent. Finally, a chromatography-crystallization hybrid separation process was proposed and tested. The results of the present work demonstrated the feasibility of combining the advantages of column chromatography and crystallization to improve efficiency of the isolation of artemisinin from Artemisia annua.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1002/ceat.200900575
DO - 10.1002/ceat.200900575
M3 - Journal article
SN - 0930-7516
VL - 33
SP - 791
EP - 796
JO - Chemical Engineering and Technology
JF - Chemical Engineering and Technology
IS - 5
ER -