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

Abstract

In this study, process integration for crystallization of a priori purified Artemisia annua L. is investigated. For this total process, the integration operation boundaries and behavior of the crystals are studied. This is performed focusing on a conceptual process design study for artemisinin, aiming towards the development of a crystallization step under given parameters by process integration. At first, different crystallization systems consisting of ethanol-water or acetone-water mixtures are compared. In subsequent steps, the metastable zone width and the behavior of the crystals regarding agglomeration and breakage are checked. Furthermore, the sensitivities of process variables based on several process parameters are investigated. Additionally, the final process integration of crystallization as a combined purification and isolation step is studied.

Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19

“…After that, the purified extract should be concentrated to at least 1/8 th its initial volume using an evaporator. The concentrated extract is submitted into a jacketed crystallization reactor (6) equipped with a stirring shaft set at tip-speed in the range of 100-150 rpm to control breakage effects and to generate a narrow particle size distribution (Huter et al., 2018 ). The cooling rate is set to 0.5 °C/min to reach 4 °C and is kept at this temperature for 60 min to let artemisinin crystals settle down.…”

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

“…Further, empirical models like quantitative structure-activity relationship (QSAR) are applied to predict the discontinuity point of proteins in presence of PEG molecules [35,36]. Moreover, model approaches derived from a mechanistic model approach for crystallization are described also for precipitation [60][61][62][63][64][65]. These models are built with population balances and contain detailed information about nucleation, birth, growth, and disruption of crystals or agglomerates.…”

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

“…Previous studies have shown that the substance could be extracted by solid-liquid extraction (SLE) using percolation or pressurized hot water extraction (PHWE) [3]. Typically, the purification is performed by liquid-liquid extraction (LLE) (see Part II) chromatography and a final crystallization (see Part IV) [3][4][5][6][7][8][9][10][11][12].…”

“…The structure of artemisinin is depicted in Figure 2, whereas a detailed description of the target component is given in (Part I). , 181, doi:10.3390/pr6100181 [12]. The schematic production process for artemisinin is shown in Figure 1.…”