1. 1 Scalable Technology for the Extraction of Pharmaceutics Group #5 Christine Spina Jeremy Katusak

2. 2 Introduction—Christine Application case studies What comes next?—Jeremy

3. 3 Introduction What is CCC? A brief history Technology Readiness Levels

4. 4 What is CCC? Counter-current chromatography Liquid-Liquid extraction Liquid-Liquid chromatography Lower downstream processing costs

5. 5 What is CCC? Advantages Quick

6. 6 What is CCC? Advantages Quick Inexpensive

7. 7 What is CCC? Advantages Quick Inexpensive Gentle and versatile

8. 8 What is CCC? Advantages Quick Inexpensive Gentle and versatile Range

9. 9 Introduction What is CCC? A brief history Technology Readiness Levels

10. 10 A brief history CCC first introduced in 1966 “I” type centrifuges 1980s “J” type centrifuges

11. 11 A brief history Brunel Institute for Bioengineering (BIB) Brunel CCC prototype

12. 12 A brief history EPSRC-IMI programme 4.6L Maxi CCC prototype

13. 13 A brief history EPSRC-IMI programme Further scale-up of the 18L

14. 14 A brief history EPSRC-IMI programme Scale down: Mini CCC prototype (5.4 or 17.8 mL)

15. 15 Introduction What is CCC? A brief history Technology Readiness Levels

16. 16 Technology Readiness Levels Brunnel: TRL4 Dynamic Extractions: TRL5-7 Current TSP-STEP: TRL 8

17. 17 Introduction—Christine Application case studies What comes next?—Jeremy

18. 18 Application Case Studies Separation of syn/anti isomers Isolation of intermediate Separation of isomers Isolation of a peroxy-substituted compound

19. 19 Separation of syn/anti isomers High-Performance Liquid Chromatography (HPLC) of crude containing 32% of target anti isomer

20. 20 Separation of syn/anti isomers HPLC of crude containing 32% of target anti isomer

21. 21 Separation of syn/anti isomers HPLC of crude containing 68% of target syn isomer

22. 22 Separation of syn/anti isomers CCC chromatogram: isolation of anti-isomer >98%

23. 23 Application Case Studies Separation of syn/anti isomers Isolation of intermediate Separation of isomers Isolation of a peroxy-substituted compound

24. 24 Isolation of intermediate HPLC of mixturecontaining 64% of starting material

25. 25 Isolation of intermediate HPLC of mixturecontaining 64% of starting material

26. 26 Isolation of intermediate HPLC of recovered target

27. 27 Application Case Studies Separation of syn/anti isomers Isolation of intermediate Separation of isomers Isolation of a peroxy-substituted compound

28. 28 Separation of isomers High-Performance Liquid Chromatography (HPLC) of crude containing 74% of target

29. 29 Separation of isomers HPLC of crude containing 74% of target

30. 30 Separation of isomers HPLC of crude containing 74% of target

31. 31 Separation of isomers HPLC of purified fraction.

32. 32 Separation of isomers HPLC of purified fraction. 98% purity.

33. 33 Separation of isomers HPLC of purified fraction. 98% purity. 95% recovery

34. 34 Application Case Studies Separation of syn/anti isomers Isolation of intermediate Separation of isomers Isolation of a peroxy-substituted compound

35. 35 Isolation of a peroxy-substitued compound Crude: 87% Purity

36. 36 Isolation of a peroxy-substitued compound Crude: 87% Purity Issue: Bromo-impurity

37. 37 Isolation of a peroxy-substitued compound Crude: 87% Purity Issue: Bromo-impurity

38. 38 Isolation of a peroxy-substitued compound Crude: 87% Purity Issue: Bromo-impurity Goals: >95% purity

39. 39 Isolation of a peroxy-substitued compound Crude: 87% Purity Issue: Bromo-impurity Goals: >95% purity AND no bromo-analogue

40. 40 Isolation of a peroxy-substitued compound Refined: 95.2% purity 59% recovered

41. 41 Introduction—Christine Application case studies What comes next?—Jeremy

42. 42 What comes next? Challenges Future goals

43. 43 Challenges Solid phase preparative chromatography

44. 44 Challenges Solid phase preparative chromatography Currently the technique of choice Well established

45. 45 Challenges Solid phase preparative chromatography Currently the technique of choice Well established Understanding the considerations

46. 46 Challenges Solid phase preparative chromatography Currently the technique of choice Well established Understanding the considerations Manufacturing scale Chromatographic processes to isolate?! Effective control

47. 47 Challenges Solid phase preparative chromatography Currently the technique of choice Well established Understanding the considerations Manufacturing scale Chromatographic processes to isolate?! Effective control Regulations

48. 48 What comes next? Challenges Future goals

49. 49 Future goals One year down, two to go!

50. 50 Future goals One year down, two to go! Rapid method development

51. 51 Future goals One year down, two to go! Rapid method development Automation

52. 52 Future goals One year down, two to go! Rapid method development Automation Continuous processing

53. 53 Future goals One year down, two to go! Rapid method development Automation Continuous processing Reliability and robustness

54. 54 References Article: Ian Sutherland, Svetlana Ignatova, Peter Hewitson, et. all, Scalable Technology for the Extraction of Pharmaceutics (STEP): The transition from academic knowhow to industrial reality, Journal of Chromatography A, Volume 1218, Issue 36, 9 September 2011, Pages 6114-6121. (http://www.sciencedirect.com/science/article/pii/S002196731100046X)http://www.sciencedirect.com/science/article/pii/S002196731100046X Images Ted: http://www.tempestfreerunning.com/ted-the-movie-tempest-makes-cameohttp://www.tempestfreerunning.com/ted-the-movie-tempest-makes-cameo Money: http://www.123rf.com/photo_1767615_pennies-on-the-dollar--one-dollar-bill-with-small- stacks-of-pennies-on-top-on-a-white-background.htmlhttp://www.123rf.com/photo_1767615_pennies-on-the-dollar--one-dollar-bill-with-small- stacks-of-pennies-on-top-on-a-white-background.html stopwatch: http://technologytom.com/html/reaction_time.html http://technologytom.com/html/reaction_time.html measuring cups http://www.gourmetsleuth.com/images/dry_measuring_cups.jpg I type: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815076/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815076/ J type: http://ars.els-cdn.com/content/image/1-s2.0-S0021967304023374-gr1.gifhttp://ars.els-cdn.com/content/image/1-s2.0-S0021967304023374-gr1.gif

55. 55 Questions?