Abstract
Liquid-liquid extraction (LLE) is an established unit operation in the manufacturing process of many products. However, development and integration of multistage LLE for new products and separation routes is often hindered and is probably more cost intensive due to a lack of robust development strategies and reliable process models. Even today, extraction columns are designed based on pilot plant experiments. For dimensioning, knowledge of phase equilibrium, hydrodynamics and mass transport kinetics are necessary. Usually, those must be determined experimentally for scale-up, at least in scales of DN50-150 (nominal diameter). This experiment-based methodology is time consuming and it requires large amounts of feedstock, especially in the early phase of the project. In this study the development for the integration of LLE in a new manufacturing process for artemisinin as an anti-malaria drug is presented. For this, a combination of miniaturized laboratory and mini-plant experiments supported by mathematical modelling is used. System data on extraction and washing distributions were determined by means of shaking tests and implemented as a multi-stage extraction in a process model. After the determination of model parameters for mass transfer and plant hydrodynamics in a droplet measurement apparatus, a distributed plug-flow model is used for scale-up studies. Operating points are validated in a mini-plant system. The mini-plant runs are executed in a Kühni-column (DN26) for extraction and a packed extraction column (DN26) for the separation of side components with a throughput of up to 3.6 L/h, yield of up to 100%, and purity of 41% in the feed mixture to 91% after washing.
Highlights
More than 12,000 plants are currently known to form a active pharmaceutical ingredient.The demand for plant-based active ingredients is expected to increase further in the coming years.There is an increasing need for natural food supplements and cosmetic products [1,2,3].A very important plant-based active ingredient is the malaria drug Artemisinin, which is derived from annual mugwort (Artemisia annua L.)
Three solvents that were suitable for liquid-liquid extraction with the extract of solid-liquid extraction (SLE extract) were initially considered
The increase of the flow rate of the continuous phase seems to have a positive influence and enables a purity of more than 90%
Summary
More than 12,000 plants are currently known to form a active pharmaceutical ingredient.The demand for plant-based active ingredients is expected to increase further in the coming years.There is an increasing need for natural food supplements and cosmetic products [1,2,3].A very important plant-based active ingredient is the malaria drug Artemisinin, which is derived from annual mugwort (Artemisia annua L.). More than 12,000 plants are currently known to form a active pharmaceutical ingredient. The demand for plant-based active ingredients is expected to increase further in the coming years. There is an increasing need for natural food supplements and cosmetic products [1,2,3]. A very important plant-based active ingredient is the malaria drug Artemisinin, which is derived from annual mugwort (Artemisia annua L.). Its strengths are its excellent biocompatibility and efficacy against the multi-resistant pathogen of malaria tropica. Malaria is one of the most common and most
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