Supercritical Fluid Technology in Drug Discovery and Development.pptx

Supercritical Fluid Technology in Drug Discovery and Development

1. Prof . (Dr.) Vimal Kumar Dean, School of Pharmacy, ITM (SLS) Baroda University & Former Associate Dean, Pharmacy, GTU, Ahmedabad [email protected] Supercritical Fluid Technology in Drug Discovery and Development

2. 65 -80 % of the world population uses traditional medicine as their primary health care - WHO estimate, Complimentary and Alternative Medicine at NIH(1996);3:3 Role of Herbal Drugs in Drug Discovery

3. Use of Traditional Medicine

4. High cost (almost US $ 2000 million), long time (15-20 years) taken in the development of any new synthetic drug. The several side effects and adverse reactions and poor success are also associated with them. Inadequate, especially in the management of certain chronic diseases like asthma and diabetes. More than 45,000 plant species found in the ecosystem of the our country and only a small percentage of plants has been investigated phyto -pharmacologically.

5. Discovery and Money:

6. It has been estimated that nearly 75,000 species of higher plants exist on the earth, and only 10% have been used in traditional medicine. Only 1 to 5% have been studied scientifically and are known to have therapeutic value

7. The herbal "shotgun" may be more effective than the “Silver bullet”

8. Dried plant material Hexane fraction Sequentially fractionated with Hexane, Ethyl-acetate and Butanol Extracted with Ethanol and water (7:3) 5 g of extract Suspended in water All the fractions collected are subjected to bioassay Subjected for bioassay Butanol fraction Ethyl acetate fraction Water fraction Extraction of Phytochemicals from Plants Pure compound Toxicology Structure elucidation Structure modification By spectroscopy By synthesis

9. Lead finding from natural resources Nature inspired drugs

10. Paclitaxel

11. Cadila Pharmaceuticals , in collaboration with the Indian Institute of Integrative Medicine (IIIM), has developed a fixed-dose combination product containing 200 mg   rifampicin , 300 mg   isoniazid  and 10 mg   piperine from Piper nigrum   for the  better treatment  of  tuberculosis .

12. Bergenia ciliata , winter begonia, Hairy Bergenia ( Hindi & Sanskrit : Pashanbheda ( पाषाणभेद) ) It is widely used in the treatment of dysuria, cystisis , crystalluria and renal failure. Bergenia ciliata is a medicinal plant used for the treatment of kidney stones.

13. Extraction : The defatted coarse powder of the Bergenia ciliata rhizomes was extracted Defatted drug powder ↓ Aqueous extract ↓   Ethyl acetate fraction ↓ Methanol fraction ( Bergenin ) Bergenin  

14. Pharmacological studies: Bergenia ciliata rhizomes exhibited : * Adrenaline potentiating effect was observed on isolated guinea pig tracheal chain with LD 50 - 650 mg/kg i.p ( Maurya et al, 1972) * Anti-asthmatic in folk medicine (Singh V. 1995) * Anti- tussive activity( Sinha et at 2001) These reports formed the strong basis for the selection of this herbal drugs for our research anti asthmatic studies Singh V . Traditional remedies to treat asthma in northwest and Trans Himalayan regions in J. & K. State. Fioterapia . 1995 ; 56(6); 507-509

15. 2020 1990

16. 75% of Indians below 40 are stressed 35% - prone to diseases Lifestyle habits are changing, common lifestyle diseases are sleeping disorders , stroke heart attack, cancers etc. Nutritional Supplements - provide a well rounded health and fitness. Times are changing…..

17. Comparison of 100gm of Moringa oleifera Lam. dried powder with other food sources

18. Supercritical Fluids Technology IN DRUG DISCOVERY

19. PRINCIPLE OF SUPERCRITICAL FLUID

20. SUPER CRITICALFLUID TECHNOLOGY (SFT) It is a cutting-edge environmentally friendly technology which makes use of supercritical fluid with multiple applications in the pharmaceutical field ranging from extraction to analysis of wide variety of herbal drugs and substances.  SUPERCRITICAL FLUID is a fluid that exists above its critical temperature T c and critical pressure P c. SUPERCRITICAL FLUID EXTRACTION (SFE) A technique for extraction of solid and liquid samples with supercritical fluid (SCF). SUPERCRITICAL FLUID CHROMATOGRAPHY (SFC) Chromatographic technique in which supercritical fluid is used as the mobile phase to separate analyzes with chromatographic columns .

21. Supercritical fluid technologies offer a propitious method for drug discovery from natural sources. Such methods require relatively short processing times, produce extracts with little or no organic co-solvent, and are able to extract bioactive molecules whilst minimizing degradation. Supercritical fluid extraction (SFE) provides a range of benefits, as well as offering routes to overcome some of the limitations that exist with the conventional methods of extraction .

22. Conventional extraction methods are not only inefficient , having a poor yield of bioactive extract relative to the high energy input, but are expensive due to the need to dispose of large amounts of organic waste, which in itself can risk environmental issues   The emergence of green chemistry for extraction purposes occurred in the 1990s with the aim of reducing energy consumption and replacing the conventional solvents with less environmentally harmful alternatives

23. PROPERTIES OF SCF Can penetrate solids like gas Dissolves materials like liquid It has a very good solvent property All supercritical fluids are completely miscible with each other. Finally the SCF recompressed & recycled. It is relatively rapid for low viscosity & high diffusivity of SCF Easily recoverable by changing pressure and temp

24. In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the Pharmaceutical Sciences. Supercritical fluid extraction using carbon dioxide (CO2) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents.

25. CO 2 AS AN SUPERCRITICAL FLUID Two Separate phases of Carbon Dioxide One Supercritical Phase Of Carbon Dioxide

26. INSTRUMENTATION Dynamic (continuous) Static (batch) Extraction vessel is constantly supplied with fresh supercritical fluid. Recovery container is continually supplied with the solute. Outlet of the extraction vessel is closed Extraction takes place without the regeneration of supercritical fluid Used when matrix is dense

27. SFE COUPLING TECHNIQUES OFFLINE SFE ONLINE (DIGITAL) SFE It involves depressurizing the supercritical fluid (SF) into a collection device An empty vessel Vessel with organic solvent A cryogenically cooled capillary It involves collection on a chromatographic instruments GC column HPLC column SFE-SFC and simultaneous analysis by Flame ionization detector Mass spectrometer

28. ADVANTAGES OF SUPERCRITICAL FLUIDS One step sample preparation Suitable for Thermolabiles Environment Friendly Safe Economic Low Toxicity Non-Flammable No Solvent Residue Enhanced solvency

29. Compressed CO 2 comes out of the nozzle, resulting fast depressurization which forms nano -particles of herbal bio-actives. Fast depressurization SFE MECHANISM

30. Techniques used to produce particles: (A) rapid expansion from supercritical solutions (RESS); and (B) particles from gas saturated solutions (PGSS)

31. APPLICATIONS OF SFE IN EXTRACTION Natural oil and flavors ß- carotenes from carrot, 5.32% , ß- carotenes oxidized in traditional extraction. SFE reduces the potential for oxidation, since CO 2 has a low critical temperature. Naturally active Phyto agents (Artemisinin, Taxol, Acidresvertrol from grapes) Nicotine, cocaine, indole and purine alkaloids Lycopene from tomato skin Piperine extraction from Black Pepper (7.00% of the Piperine) Separation of Cumin Seed Oil Constituents

32. Fractionation and purification of volatile oils, (citrus oil into different classes) SFE has been online coupled with SFC for the determination of actractylon in Actractylodes rhizome Cholesterol from meat and dairy products. Caffeine from coffee and tea. As well as to decaffeinate the coffee powder Stevioside from Stevia plant Baicalein and baicalin from Scutellaria root Ginger extracts with high content of up to 40% essential oil and up to 30% pungent gingerols

33. Lutein from marigold flowers Extraction of Fragrances from Jasmine Flowers Clove Oil Extraction from Clove Triglyceride Extraction from Soybeans High Quality Aloe Vera Gel from Aloe by Using Supercritical Carbon Dioxide. Asiaticoside from Centella asiatica (L.) CO 2 vanilla extracts are is containing up to 95% of natural vanillin and more concentrated than normal hydro-alcoholic vanilla extracts.

34. A GREEN PROCESSING IN NUTRACEUTICALS Nutraceuticals, as the name suggests, are ingested substances which combine the benefit of food nutritional requirements while offering Some aspect of therapeutic protection to the human body. Such foods and natural substances are called functional foods, designer foods, pharma foods etc. Critical fluid processing can be used in several modes for producing nutraceutical ingredients or functional foods. Rice bran oil n-6, n-3 Fatty acids Oat oil Tocotrienols Wheat germ Sesamolin Ginseng Tonic Ginko biloba Circulatory Diseases Garlic Circulatory Diseases Tocopherols Antioxidant

35. SCF Chromatography

36. Application of SFE in Various Field

37. CONCLUSION Over the last few decades, Supercritical Fluid Extraction (SCFE) Technology has emerged as a superior alternative to the conventional techniques (solvent extraction or steam distillation etc ). However, there is still a very large potential for the use of SFT to achieve better value addition and to generate preference for quality natural products, as compared to the traditionally processed natural products that may undergo degradation during conventional processing steps, due to incorporation of heat, oxidation, hydrolysis etc.  

38. In view of India’s rich botanical and marine resources, SFT has high potential in producing nutraceuticals, foods, flavors, fragrances, cosmetics, and biologically active principles ( Phyto -pharmaceuticals) from Natural sources and there by achieving a significant value addition in their export.

39. The use of supercritical fluids such as scCO2 has provided a clean alternative to traditional techniques that employ toxic organic solvents or elevated temperatures. This technology can play an important role in future Pharma / Herbal Industry

40. Thus, use of the Supercritical Fluid Technology can help Indian Pharma Industry to gain its share in rapidly growing international market for high quality and value added products.

41. T he world is always gifted with nature, and man is gifted with brain, so let us make use of it to discover new entities that will be available to common people in economical rate and we will be happy to lead a life on this earth.  

42. Indian Company in SFT…… Constructive step by Dr. Swapneshu Baser Deven Supercriticals Pvt. Ltd. Mumbai Dr. Baser was associated with SCFE technology development activity at IIT-Bombay since its inception in 1993. Presently offer wide range of technologies / equipment in the field of Supercritical Fluid processing.

43. 45 If we want to make the claims… Then we have to do science…. ….with our product! Develop New strategies & Work together with cooperation and coordination!! SFT in Drug Discovery : yet to be explored !

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