Process design for integration of extraction, purification and formulation with alternative solvent concepts

Abstract

Methods of Green Chemistry are in the meantime established in process design for extraction of natural products [1]. Moreover, natural products do have the inherent societal benefit of being a priori bio-degradable and therefore do not cause any additional wastewater and recycling problems in hospitals, cities and municipalities or environmental enrichment [2]. Nevertheless, those inherent benefits could be easily compromised if they are not combined with the design and operation of fully integrated processes in manufacturing. One isolated action of Green Chemistry is not sufficient to gain the entrepreneurial balance of economy and ecology with competitive manufacturing, new marketable products, and sustainability. While any process modification could be implemented in substituting simply one existing step, a fully integrated new process needs to be set up to exceed the existing benchmark or best practice and to be transferred into manufacturing. Finding alternative solvents and enhancing mass transfer in extraction need to be integrated. This integration into a complete process from extraction over purification to formulation, considering recycling at all steps, is a complex task which could not be fulfilled on a purely experimental basis. The efforts would be too high and costly. Therefore, the paper reviews the existing status shortly and exemplifies based on a case study, choosing 10-deacetylbaccatin III as a typical example, a theoretical approach in thermodynamics and process modeling, and how they can contribute to an alternative process design. Still, these steps in conceptual process design and basic engineering seem to be the major challenge in industrial acceptance of alternative ideas. The authors have described the transfer into innovative manufacturing concepts already elsewhere [1e3].

Systematic and Model-Assisted Evaluation of Solvent Based- or Pressurized Hot Water Extraction for the Extraction of Artemisinin from Artemisia annua L.

“…This might be due to a highly complex side component spectrum that is extracted with every single solvent system. It is likely that these spectra influence the solubility of artemisinin over a wide range due to natural solubilizing effects, that have been observed for other extracts as well [6]. The combination of experimental model parameter determination and rigorous process model is a suitable way for predictive process simulation.…”

“…Because artemisinin is a product with high added value, a complete leaching is desirable. Therefore, percolation is chosen for this study [3,4,6,29].…”

“…Another substance is the anti-malaria agent artemisinin from annual mugwort (Artemisia annua L.). These substances are extracted from the plant matrix and afterwards purified to pharma grade, typically by liquid-liquid extraction, chromatography, and a final crystallization [3][4][5][6]. They are commonly applied as a pure substance and the whole complexity of the crude plant extract is neither desired nor is it approved.…”

Quality-by-Design (QbD) process evaluation for phytopharmaceuticals on the example of 10-deacetylbaccatin III from yew

“…Solvent screening for modeling and optimization has shown suitable solubility in solvents like acetone and ethanol [20].…”

“…The purity is defined as the amount and number of other components with similar elution properties during the final separation in relation to the target component, as established in a previous work [20].…”