1

Scalable Technology for the Extraction of Pharmaceutics

Group #5

Christine Spina

Jeremy Katusak

2

• Introduction—Christine

• Application case studies

• What comes next?—Jeremy

3Introduction

• What is CCC?

• A brief history

• Technology Readiness Levels

4What is CCC?

• Counter-current chromatography• Liquid-Liquid extraction• Liquid-Liquid chromatography

• Lower downstream processing costs

5What is CCC?

• Advantages• Quick

6What is CCC?

• Advantages• Quick

• Inexpensive

7What is CCC?

• Advantages• Quick

• Inexpensive

• Gentle and versatile

8What is CCC?

• Advantages• Quick

• Inexpensive

• Gentle and versatile

• Range

9Introduction

• What is CCC?

• A brief history

• Technology Readiness Levels

10A brief history

• CCC first introduced in 1966• “I” type centrifuges

• 1980s• “J” type centrifuges

11A brief history

• Brunel Institute for Bioengineering (BIB)• Brunel CCC prototype

12A brief history

• EPSRC-IMI programme• 4.6L Maxi CCC prototype

13A brief history

• EPSRC-IMI programme• Further scale-up of the 18L

14A brief history

• EPSRC-IMI programme• Scale down: Mini CCC prototype

(5.4 or 17.8 mL)

15Introduction

• What is CCC?

• A brief history

• Technology Readiness Levels

16Technology Readiness Levels

• Brunnel:• TRL4

• Dynamic Extractions:• TRL5-7

• Current TSP-STEP:• TRL 8

17

• Introduction—Christine

• Application case studies

• What comes next?—Jeremy

18Application Case Studies

• Separation of syn/anti isomers

• Isolation of intermediate

• Separation of isomers

• Isolation of a peroxy-substituted compound

19Separation of syn/anti isomers

High-Performance Liquid Chromatography (HPLC) of crude containing 32% of target anti isomer

20Separation of syn/anti isomers

HPLC of crude containing 32% of target anti isomer

21Separation of syn/anti isomers

HPLC of crude containing 68% of target syn isomer

22Separation of syn/anti isomers

CCC chromatogram: isolation of anti-isomer >98%

23Application Case Studies

• Separation of syn/anti isomers

• Isolation of intermediate

• Separation of isomers

• Isolation of a peroxy-substituted compound

24Isolation of intermediate

HPLC of mixturecontaining 64% of starting material

25Isolation of intermediate

HPLC of mixturecontaining 64% of starting material

26Isolation of intermediate

HPLC of recovered target

27Application Case Studies

• Separation of syn/anti isomers

• Isolation of intermediate

• Separation of isomers

• Isolation of a peroxy-substituted compound

28Separation of isomers

High-Performance Liquid Chromatography (HPLC) of crude containing 74% of target

29Separation of isomers

HPLC of crude containing 74% of target

30Separation of isomers

HPLC of crude containing 74% of target

31Separation of isomers

HPLC of purified fraction.

32Separation of isomers

HPLC of purified fraction.

98% purity.

33Separation of isomers

HPLC of purified fraction.

98% purity.

95% recovery

34Application Case Studies

• Separation of syn/anti isomers

• Isolation of intermediate

• Separation of isomers• Isolation of a peroxy-substituted compound

35

Isolation of a peroxy-substitued compound

Crude: 87% Purity

36

Isolation of a peroxy-substitued compound

Crude: 87% Purity

Issue: Bromo-impurity

37

Isolation of a peroxy-substitued compound

Crude: 87% Purity

Issue: Bromo-impurity

38

Isolation of a peroxy-substitued compound

Crude: 87% Purity

Issue: Bromo-impurity

Goals: >95% purity

39

Isolation of a peroxy-substitued compound

Crude: 87% Purity

Issue: Bromo-impurity

Goals: >95% purity AND

no bromo-analogue

40

Isolation of a peroxy-substitued compound

Refined: 95.2% purity

59% recovered

41

• Introduction—Christine

• Application case studies

• What comes next?—Jeremy

42What comes next?

• Challenges

• Future goals

43

Challenges

• Solid phase preparative chromatography

44

Challenges

• Solid phase preparative chromatography• Currently the technique of choice• Well established

45

Challenges

• Solid phase preparative chromatography• Currently the technique of choice• Well established

• Understanding the considerations

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

Challenges

• Solid phase preparative chromatography• Currently the technique of choice• Well established

• Understanding the considerations

• Manufacturing scale• Chromatographic processes to isolate?!• Effective control

• Regulations

48What comes next?

• Challenges

• Future goals

49

Future goals

• One year down, two to go!

50

Future goals

• One year down, two to go!

• Rapid method development

51

Future goals

• One year down, two to go!

• Rapid method development

• Automation

52

Future goals

• One year down, two to go!

• Rapid method development

• Automation

• Continuous processing

53

Future goals

• One year down, two to go!

• Rapid method development

• Automation

• Continuous processing

• Reliability and robustness

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)

• Images

Ted: http://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.html

stopwatch: 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/

J type: http://ars.els-cdn.com/content/image/1-s2.0-S0021967304023374-gr1.gif

55

Questions?