Highly Efficient Artemisinin Extraction with Sonication

Artemisinin can be efficiently extracted using high-performance sonication. Ultrasonic extraction gives very high yields of artemisinin using mild solvents. The process of extraction applying ultrasound is accelerated drastically. The processing conditions in ultrasonic extractors are precisely controllable, which allows to prevent degradation of the heat-sensitive biomolecule artemisinin.

Artemisinin Extraction

Artemisinin is a bioactive molecule present within the trichome glands of the Artemisia annua plant, which is used as anti-malaria drug and shows high potential as drug for the treatment of several other diseases including cancer and SARS-CoV-2. The traditional extraction method involves toxic solvents and is an expensive, sub-optimal process. In order to produce artemisinin on large scale under environmentally and economically favourable conditions, an efficient and green extraction technique is required. Ultrasonic extraction is a widely established extraction method that can be used in combination with water or ethanol as non-toxic solvents. Ultrasonic extraction has been already proven to hive high artemisinin yields, so that artemisinin production can be rapidly scaled to large volumes. Ultrasonic extraction equipment for batch and in-line processing on industrial level is readily available.

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Ultrasonic extractor for artemisinin extraction under pharma-grade conditions.

Ultrasonic extractor UIP2000hdT for industrial batch-extraction of artemisinin from Artemisia annua leaves.

Ultrasonic Extraction of Artemisinin from Artemisia annua

The use of power ultrasound for the extraction excels other extraction methods in various major factors, including yield, extraction time, environmental-friendliness, and cost-efficiency.

Ultrasonic Homogenizer UP400St for the agitated batch extraction of botanicals.

Ultrasonic Extraction of Botanicals - 8 Liter Batch - Ultrasonicator UP400S

The Drawbacks of Traditional Artemisinin Extraction

Traditional extraction methods for artemisinin are time-consuming, can damage the bioactive molecules artemisinin due to high temperatures applied, and have a high environmental impact due to the organic solvents used at high temperatures. Additionally, in the downstream process extensive purification is necessary to remove impurities from the crude extract.

The Advantages of Ultrasonic Artemisinin Extraction

Applying power ultrasound for extraction has several positive effects which intensify the extraction process: High-performance ultrasound creates acoustic cavitation. This acoustic cavitation promotes botanical extraction by cell disruption, so that the entrapped biomolecules are released from the cell matrix of the plant. Additionally, the cavitational forces intensify mass transfer transporting the biomolecules such as artemisinin efficiently into the surrounding solvent. The working principle of ultrasonic extraction can be contributed to purely mechanical forces of cavitation. This means sonication is a non-thermal, non-chemical extraction technique. Being a non-thermal extraction technique makes ultrasonic extraction especially favourable since artemisinin is a thermally sensitive compound, meaning higher temperatures (e.g., 70°C) will cause its decomposition. Consequently, Artemisia annua L. could not be boiled in hot water to obtain artemisinin.

Benefits of Ultrasonic Artemisinin Extraction

  • Higher yields
  • Superior quality
  • Rapid extraction
  • Choose your preferred solvent
  • No thermal degradation
  • Works with fresh and dried leaves
  • Precisely controllable conditions
  • Cost-efficient

Green Solvents for Ultrasonic Artemisinin Extraction

Classical extraction solvents used for artemisinin production include hexane, petroleum ether or dichloromethane. Ultrasound-driven extraction is compatible with any solvent including mild, green solvents such as ethanol or water. Ultrasonic extraction of artemisinin with ethanol is equally efficient when compared to harsh solvents. As artemisinin exhibits poor water-solubility cyclodextrins can be used to improve the ultrasonic cold-water extraction of artemisinin.

This video shows the 100 watts ultrasonic homogemizer UP100H for extraction of botanicals.

Ultrasonic Extraction of Bioactive Compounds

What Makes Ultrasonic Artemisinin Extraction So Efficient?

To understand the advantages of ultrasonically assisted extraction, the working principle of power ultrasound must be understood. The extraction intensifying mechanism of power ultrasound is mainly attributed to the phenomenon of acoustic cavitation. Ultrasonic cavitation causes collisions between particles of the botanical biomass (such as Artemisia annua L. leaves), which results in interparticular fractioning and reduction of particle size. When cavitation bubbles collapse on the surface of the vegetable solids, erosion and sonoporation enlarge the particle surface further. The thereby intensified mass transfer facilitates the release of molecules such as proteins, lipids, sugars, vitamins, antioxidants, phyto-chemicals (e.g., artemisinin) and dietary fibres. Ultrasonically generated shear forces improve the penetration of the solvent into the cellular matrix of the botanical matter and improve the permeability of the cell membranes, respectively. These mechanisms of power ultrasonics are responsible for the significant process intensification achieved when ultrasonication is applied for botanical extraction.

Ultrasonic extraction is works by disrupting cell structures and promoting mass transfer

Power ultrasound waves disrupt the cell structure of botanicals, release the bioactive compounds and promote the mass transfer between the plant material and the solvent (e.g., ethanol).

Ultrasonic probe deice UP400St for the extraction of artemisinin from Artemisia annua trichomes.

Ultrasonicator UP400St (400 watts) for batch-extraction of artemisinin.

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Research-Proven Results of Ultrasonic Artemisinin Extraction

Several scientific studies have been undertaken in order to investigate the efficiency and practicability of ultrasonic artemisinin extraction from Artemisia annua leaves.

Briars and Paniwnyk showed “that ultrasound at low temperatures increases the yield of artemisinin extracted from A. annua by around 58% and the extracts appear purer when compared to conventional steeping; therefore the use of ultrasound during extraction has the potential for producing lower cost artemisinin-based treatments.” (Briars and Paniwnyk, 2013)

Zhang et al. (2017) investigated ultrasonic artemisinin extraction using propylene glycol methyl ether (PGME) as solvent. Ultrasonically produced artemisinin extract was analysed using Ultra Performance Liquid Chromatography (UPLC). Analysis results underlined the quality of the extract. Due to the good process repeatability and stability of extracted artemisinin, the ultrasonically assisted extraction using the green and efficient monoether propylene glycol methyl ether (PGME) as solvent shows great prospects in the extraction and separation of bioactive molecules from botanicals. Ultrasonic extraction using propylene glycol methyl ether (PGME) as solvent resulted in high overall extraction efficiency and high artemisinin yields. (cf. Zhang et al., 2017)

In another study, Zhang et al. (2020) present the ultrasonic extraction of artemisinin using hydroxypropyl-β-cyclodextrin. The addition of cyclodextrin improves the release of the poorly water-soluble compound artemisinin and allows to use water as solvent with good extraction yields. Ultrasonic extraction in combination with cyclodextrin increased the artemisinin amount to 8.66 mg/g, which is significantly more than the corresponding amount of 1.70 mg/g obtained in water.

High Performance Ultrasonic Extractors for Artemisinin Production

Ultrasonic extractor UIP2000hdT (2000 watts) during botanical extraction such as artemisinin from Artemisia annua leaves.High-performance ultrasonic extraction systems from Hielscher Ultrasonics are used worldwide on R&D, small, mid-size and fully-commercial production levels in various industries such as in food, dietary supplement and pharmaceutical production. High-performance ultrasonic extractors intensify the extraction process and increase yield thereby improving the overall-efficiency of high-quality extract production. Hielscher Ultrasonics offers extraction equipment for any volume / process capacity. Having experience in botanical extraction for more than 25 years, Hielscher Ultrasonics is your trusted partner for high-performance ultrasonic extraction from Artemisia annua!

High-Performance, State-of-the-Art Ultrasonicators

The smart features of Hielscher ultrasonicators are designed to guarantee reliable operation, reproducible outcomes and user-friendliness. Operational settings can be easily accessed and dialled via intuitive menu, which can be accessed via digital colour touch-display and browser remote control. Therefore, all processing conditions such as net energy, total energy, amplitude, time, pressure and temperature are automatically recorded on a built-in SD-card. This allows you to revise and compare previous sonication runs and to optimize the artemisinin extraction process to highest efficiency.
Hielscher Ultrasonics systems are used worldwide for the manufacturing of high-quality botanical extracts. Hielscher industrial ultrasonicators can easily run high amplitudes in continuous operation (24/7/365). Amplitudes of up to 200µm can be easily continuously generated with standard sonotrodes (ultrasonic probes / horns). For even higher amplitudes, customized ultrasonic sonotrodes are available. Due to their robustness and low maintenance, our ultrasonic extraction systems are commonly installed for heavy duty applications and in demanding environments.

Contact us now to learn more about ultrasonic extraction of artemisinin from the Artemisia annua plant. We would be glad to send you information about our ultrasonic extraction systems and pricing! Our well-experienced staff will be glad to discuss your application and processing requirements with you!
The table below gives you an indication of the approximate processing capacity of our ultrasonicators:

Batch Volume Flow Rate Recommended Devices
1 to 500mL 10 to 200mL/min UP100H
10 to 2000mL 20 to 400mL/min UP200Ht, UP400St
0.1 to 20L 0.2 to 4L/min UIP2000hdT
10 to 100L 2 to 10L/min UIP4000hdT
n.a. 10 to 100L/min UIP16000
n.a. larger cluster of UIP16000

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Ultrasonic high-shear homogenizers are used in lab, bench-top, pilot and industrial processing.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers for mixing applications, dispersion, emulsification and extraction on lab, pilot and industrial scale.

Literature / References

High performance ultrasonics! Hielscher's product range covers the full spectrum from the compact lab ultrasonicator over bench-top units to full-industrial ultrasonic systems.

Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers from lab to industrial size.