Aretemisinin Production In India Problems and Experience
WHO/MMV Artemisinin Conference 28 30 th Sept ‘ 2009, Mumbai, India
Dr.D.C.Jain Green Technology Department
Ipca Laboratories Ltd, Mumbai, India
Ipca
Ipca Laboratories Limited, Ratlam
Ipca
Ipca
Objective Mission Objective Mission
Artemisinin is a future drug of choice.
Artemisia annua is a plant of future.
New source of anticancer drug
Avoid dependency by own sourcing
Consistency in Quality
Cultivation increases the rural employment.
Ecofriendly
Saving of life
Cheaper cost of ACT’s and Formulation
By products : Fuel / Bio fertilizers / Mosquito repellentIpca
Artemisia Introduced in India & Development
Artemisia annua plant introduction in India (CIMAP) ) 198586 Commercially viable variety developed 1990,97 & 2001 (Asha, Jeevanraksha and CIMArogya Cultivaton Technology transfered to Ipca & other companies 2000 onwards
Ipca
Ipca initiated the cultivation 200102Commercial Cultivation 200506Cultivation in different states of country 300 Hac
Major Achievements :Average dry leaves yield /ha 1.82 tones/Hac Average artemisinin content 0.8%Recovery of artemisinin 70 – 72 %New area of cultivation (South India)
Ipca
ArtemisiArtemisiaa Journey At IpcaJourney At Ipca
Challenges To Production Of ArtemisininChallenges To Production Of Artemisinin
Higher cost of raw material (Dry Artemisia leaves)
Low content of artemisinin
High cost of production
Major impurity of artemisinin
Prices fluctuation.
Lower recovery of artemisinin
Artemisinin is very sensitive molecule
Ipca
Commercial Cultivation Of Artemisia Annua Commercial Cultivation Of Artemisia Annua
Under stand cultivation International Scenario by visits.Under stand cultivation International Scenario by visits.
Development of Technology as per Indian conditionsDevelopment of Technology as per Indian conditions
Popularization of cultivation through exhibitionPopularization of cultivation through exhibition
Free seed distribution Free seed distribution
Technical input, regular observation at field.Technical input, regular observation at field.
Contract for buy back guarantee Contract for buy back guarantee
Purchase price declared before cultivation Purchase price declared before cultivation
Incentive to farmer for higher AMS content. Incentive to farmer for higher AMS content.
Transportation cost of leaves bear by company Transportation cost of leaves bear by company
R & D work for improve biomass & AMS content.R & D work for improve biomass & AMS content.
Insure payment within 15 days Insure payment within 15 days
Seed quality Improvement continuouslySeed quality Improvement continuously
Faster analysis method developed for artemisinin analysis in plant. Faster analysis method developed for artemisinin analysis in plant.
Packing material supplied by companyPacking material supplied by company. . Ipca
Ipca
Field View Of Artemisia Annua Field View Of Artemisia Annua
Artemisia Cultivation In Different States Of IndiaArtemisia Cultivation In Different States Of India
Gujarat, Madhya Pradesh, Uttar Pradesh, Uttaranchal, , Rajashtan, Karnataka, Tamil Nadu
“Now approaching BioTechnology through cultivation of Artemisia Annua plant”
Artemisia Plant Developed By Tissue Culture Artemisia Plant Developed By Tissue Culture ( Lab To Field ( Lab To Field ) )
Ipca
Mr.Malcolm Cutler Visited Ipca in May ‘2009
Ipca
Field Vist Baroda Green Tech Lab,Ratlam
Our Experience In CultivationOur Experience In Cultivation
Ipca
Year wise Artemisia annua dry leaves productionYear wise Artemisia annua dry leaves production
0.902.0570.0148.22007083
0.811.80225.0405.92006072
0.761.20267.0320.02005061
Average % AMS
Content
Leaves Yield
(Tons/Ha.)
Area of Cultivation
(Ha.)
Leaves Production
(Tons)
YearS. No.
Ipca
Importance of analysis of Artemisinin in plantImportance of analysis of Artemisinin in plant
Analysis of Artemisinin in plant (Artemisia annua) is a very tedious work but ishaving a lot of information which are associated with it.
Information associated with analytical part: Vegetative growth Vs Artemisinin content. Development of proper harvesting time. Quantification of losses in post harvest handling. Commercial value of plant. Selection of higher yielding plants to maintain a consistent quality raw
material for the production of Artemisinin. Based on the selection high yielding plants developed. A good quality plant
variety as well as seeds. Seasonal & geographical variations in Artemisinin content Vs foliage
production study. Stability study raw material during storage. Faster analysis required during purchase of Raw material for faster payment
to farmers. Monitoring of batch extraction process.
Ipca
Fast MW – HPTLC Based Analytical MethodFast MW – HPTLC Based Analytical Method
Parallel screening of 1012 samples in 1 hour. Plant material with an unknown artemisinin content can be analyzed reliably
over a wide range of concentration. Visible output and multi samples can be compared easily. Similarity and
differences are immediately apparent. Fingerprintdeveloped and adulteration can be checked. HPTLC Plates are disposed off after use, eliminating problems associated with
ghost peak (s) appearance as occurs in routine with HPLC columns. Large number of samples can be analyzed quickly making HPTLC, a fast and
efficient solution for plant verity development. Suitable for batch processing of artemisinin. cGMP Compliance. Cost Efficiency:
Multiple sample analysisMultiple sample analysis No startup time.No startup time. Minimum quantity of solvent needed. (No costly solvent usage) Minimum quantity of solvent needed. (No costly solvent usage)
Ipca
Better recovery of ArtemisininBetter recovery of Artemisinin Cost of Artemisinin is depends upon recovery
Best recovery – Above 70% Average 60% Bad 40 % Our recovery is 70 % New technology developed & applied for better recovery
Extraction time reduction through Ultrasonic, Indigenous developed . from Lab .to Commercial scale
Crude enrichment 50% through Liquid Liquid extraction
Purification of AMS No Crystallization but chromatography to achieved quality material.
Reuse of solvent & adsorbent
Better recovery of Artemisinin during purification.
Ipca
Enrichment of Artemisinin in Crude Extract Enrichment of Artemisinin in Crude Extract
Major impurity in the extract fats/wax/pigment/chlorophyll etc Different process applied :
( 1 ) Defatting ( 2 ) Crystallization
Loss of Artemisinin Better option is Liquid – Liquid Extraction :
Removal of 50% impurity Minimum Loss of Artemisinin No solvent Loss. Time saving. Equipment used in any herbal products. Automatic system
Advantage Enrichment of Artemisinin Better crystallization/ recovery Reduced Load to Column.
Ipca
Ultrasonic – Assisted ExtractionUltrasonic – Assisted Extraction
Choice For Extraction Choice For Extraction Selective extraction compared to other techniques
Versatile technique that allows small scale to large scale.
Short extraction times & rooms temperature operation.
Avoiding damage of temperature sensitive compounds.
Improved yield can be extracted in comparison to other methods.
Excellent solution for extraction of phytochemicals.
Inexpensive and efficient alternative to conventional method.
Microbial and enzyme in activation.
Cheaper an easier operation compare to other techniques.
Ipca
TrichomeTrichome High Speed JetHigh Speed Jet
Why Faster ExtractionWhy Faster Extraction
UltrasoundAssisted extraction work upon the principle of penetration, disruption of
tissues and solublizaton of plant metabolites. With Ultrasound, Cavitation bubbles collapse near herb cell walls creating shock waves & liquid jets that cause the cell
walls to break and release their content into the solvents, speeding up and improving
the diffusion process that under normal solvent extraction condition is very slow.
Ipca
Year wise production of Artemisinin based Products Year wise production of Artemisinin based Products
Ipca
Artemether Artesunate ab Arteether ArtemotilArtesunate
sterile TOTAL of arte product Artemisinin artmisinin
YEAR QTY (In kg) QTY (In kg) QTY (In kg) QTY (In kg) QTY (In kg) production purchased 199899 127.00 127.00
19992000 147.00 12.00 1.00 160.00 200001 219.00 13.00 16.00 1.25 249.25 200102 322.00 102.00 68.00 2.25 494.25 0.60 200203 313.00 600.00 130.72 9.00 1,052.72 13.00 1530200304 423.53 3,132.39 599.73 6.14 53.69 4,215.48 20.68 5,963.00 200405 442.00 2,231.00 885.00 64.00 112.00 3,734.00 115.00 4,055.00 200506 848.00 6,045.00 1,185.00 112.00 150.00 8,340.00 309.00 9,078.00 200607 1,777.00 6,339.00 2,166.00 106.00 240.00 10,628.00 1,121.29 12,600.00200708 2,590.00 9,056.00 2,080.00 46.00 427.00 14,199.00 1,416.00 14,497.00
20082009 4,444.00 19,438.00 2,759.33 29.69 340.58 27,012.10 1,565.00 31,200.00
FROM 199899 TO 200809
Ipca
GREEN TECHNOLOGY TEAM MEMBERSGREEN TECHNOLOGY TEAM MEMBERS
Ipca Laboratories Ltd,Mumbai, India