Crystallization of Artemisinin from Chromatography Fractions of Artemisia annua Extract

Abstract

Crystallization is an inevitable step in the purification of artemisinin either from the plant Artemisia annua or from reaction mixtures of semisynthetically produced artemisinin. Rational design of crystallization process requires knowledge about the solid–liquid equilibrium in a given solvent system and effect of impurities on it. In the present work, a crystallization process was designed to purify artemisinin from fractions of a flash chromatography column effluent collected after injecting extracts of Artemisia annua leaves. The fractions from chromatography containing artemisinin were combined together into one fraction, and the impurities present in this fraction were identified. The solubility of artemisinin in the mobile phase used for chromatography, i.e., n-hexane–ethyl acetate mixture of varying compositions, was measured at 25, 15, and 5 °C, respectively. The collective effect of impurities present in the combined fraction on the solid–liquid equilibrium of artemisinin was evaluated by measuring the solubility of artemisinin in the combined fraction at same temperatures. The results show that the impurities present in the combined fraction increase the solubility of artemisinin. Finally, the crystallization of artemisinin from the combined fraction designed on the basis of artemisinin solubility data was carried out in two steps by adding an antisolvent and cooling crystallization. The yield of artemisinin obtained in the process was 50%, and it was found that the impurities present in the combined fraction at a given concentration do not affect the crystallization of artemisinin.

Systematic and Model-Assisted Process Design for the Extraction and Purification of Artemisinin from Artemisia annua L.—Part IV: Crystallization

“…Raw Artemisia annua L. and purified artemisinin (CfM Oskar Tropitzsch, Markredwitz, Germany) are used for this study. The raw plant material is ground to approximately 1 mm with a Crystallization is a typical final purification and isolation step preparing for formulation steps of plant-based or semi-synthetical processes, e.g., artemisinin [11][12][13][14][15][16][17][18][19][20][21][22][23]. The crystallization step itself is affected in various ways, based on mechanical and thermodynamic influences, e.g., [24].…”

“…An integration of the crystallization step provides financial advantages, due to its low operation costs. By integrating the crystallization step into the downstream of artemisinin as a purification step, the composition of the feed solution is essential, because of the influences of side components on solubility and kinetics [15][16][17]26,32,42,43]. With the shift of the crystallization step to earlier stages, it becomes more affectable by the variability of the side component spectrum, which is a significant factor for plant-based material.…”

Systematic and Model-Assisted Process Design for the Extraction and Purification of Artemisinin from Artemisia annua L.—Part III: Chromatographic Purification

“…The corresponding chromatograms for the measurement of the retention times at 5 vol %, 20 vol % and 30 vol % ethyl acetate are not given in this publication. The solubility of the artemisinin at the chosen ethyl acetate/n-hexane ratio is taken from Malwade et al [19]. A gradient method would push the artemisinin and the SC2 component together into one peak because these two components will change their elution order.…”

“…One is the purification of the extract using a solid-liquid extraction (SLE). Most of the studies perform a chromatographic purification followed by a crystallization step [17][18][19][20]. Moreover, the pre-purification using crystallization followed by a final chromatographic step is possible [21,22].…”

Technoeconomic optimisation and comparative environmental impact evaluation of continuous crystallisation and antisolvent selection for artemisinin recovery

“…For commercial implementation, there are important considerations for crystal size distribution and morphology, which are strictly specified by pharmaceutical product regulations (Desiraju and Nangia, 2016). For further design and analysis towards industrial implementation, comprehensive experiments elucidating artemisinin crystal growth kinetics and mechanisms are required (Malwade et al, 2013(Malwade et al, , 2016. The use of COBC units promises significant benefits, as it has been reported to offer excellent control over crystal formation and growth (McGlone et al, 2015) (Fig.…”