Results of New Purification Technology on Increasing. Costs
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- Reginald Webster
- 5 years ago
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1 Results of New Purification Technology on Increasing Production Efficiency and Reducing Costs Colin Hill And Bhupinder Khambay Extraction Technology Developments Limited and Kamtech Technologies Limited
2 Purification Challenge Primary Extracts contains only circa 10% to 30% Artemisinin Up to 90% primary extract is co-extracted ballast of no interest Ballast is mixture of polar and non polar compounds (50:50) Some compounds act as crystallisation inhibiters others co-crystallise with artemisinin
3 Purification Improvement Objective To remove either the polar or non polar fraction in a single step To ideally remove the polar fraction as this contains compounds that t cocrystallise with artemisinin
4 Current Purification Research Work Liquid / Liquid Extraction Absorbantsb CO2 / HFC
5 Liquid / liquid Widely used technology Low Capital Cost Simple technology to operate
6 Liquid / Liquid Extractors circa 1950
7 Liquid / Liquid circa 2010
8 Liquid / Liquid Results Achieving better than 75% artemisinin recovery difficult without either prejudicing purity or increased solvent use Suitable technology for use with hexane or ethanol primary extracts as starting material Not suitable technology for use with toluene primary extract (unless desolventised) as starting material Disadvantage still requires other purification steps prior to crystallisation
9 Absorbants Absorbants: Celite, Silica (including synthetic), silica gel, amberlite resins, Cranfield polymer, activated carbon, Solvents: Hexane, heptane, methanol, ethanol, ethyl acetate, propyl acetate Extract used for all the experiments was hexane extract supplied by ABE Kenya
10 Absorbants: Experimental Aims Distribution of recovered material in the two eluting solvents to be approximately 2:1 to reflect substantial removal of impurities on the basis that the crude Artemisinin extract contains 1:1:1 ratio of less-polar impurities: Artemisinin: more- polar impurities. >90% ART concentration in one of the eluting solvent fractions.
11 Absorbants:Results Silica gel, amberlite resins, activated carbon and Cranfield polymer all met the experimental aim criteria: Activated carbon found to have the best potential Hexane or heptane together with ethanol or methanol found to be best solvents regimes
12 HFC / CO 2 Ethanol Extract (from Michaela Von Freyhold (carried out 2008) Hexane Extract (from African Botanical Extracts) t Toluene extract (from Bionexx)
13 Typical CO 2 Extraction Process Expansion Valve Evaporator Condenser Separator Extraction Vessels Extract Collection CO 2 Tank CO 2 Pump Heater Sub-cooler
14 CO 2 Extraction Plant
15 HFC Primary extract pre-coated onto inert filler at around 1:1 extract to filler ratio) Charged into Extractor Extracted till approx 35% weight yield achieved Mother Liquors filtered to give crude crystals Single re-crystallisation sat Extractions have been carried out a 500ml, 19 litre, 30 litre and 500 litre scale
16 HFC Results Extraction requires approx 10 volumes of HFC to be circulated Recovery artemisinin >90% Concentration of artemisinin in recovered extract increased threefold (>30%) Almost all polar impurities removed Single re-crystallisation step gave >90% purity
17 19 litre scale HFC plant
18 30 litre scale HFC Plant
19 500 litre scale HFC Plant
20 Primary Extract / Filler in Extractor
21 Recovered Extract in HFC Evapourator
22 Recovered Extract
23 Recovered Extract
24 Recovered Extract and Crystals
25 Conclusions HFC Technology probably the simplest purification protocol presently available Advantages: Both low capital cost & low running costs Disadvantage: Cost of solvent (US$15.00 /kilo) 3 x 1000 HFC litre plant: 25 tons pure artemisinin per annum Cost approx US$600,000 (depending on infrastructure already in place)
26 Acknowledgements: MMV African Botanical Extracts t (Kenya) Bionexx (Madagascar) Dr Michaela Von Freyhold