1. Product Drying and Recovery Scott MacLean CHEE 450 April 2, 2004

2. Goals of Drying Stage Recover product Ensure it is intact/usable Minimize losses Minimize costs Maximize shelf life

3. Options Tray Drying Freeze Drying Spray Drying

4. Known Information Recover 190kg Insulin Crystal, 1.4 kg Insulin, 0.6 kg Water per batch Ultrafilter, centrifuge are previous process steps for removal of water

5. Assumptions Ultrafilter and Centrifuge reduce water to 30% by weight Process requires a continuous drying stage when in operation All other volatile components removed prior to drying stage

6. Drying Stage Flow Diagram

7. Freeze, Tray, or Spray – A Question of Stability Insulin is a Protein Zn-Insulin Crystals are stable below ~60 o C Above 60 o C, begins to denature Heat disrupts hydrogen bonds, causing vibrations  Think of egg frying

8. Tray Drying – Is it hot in here, or is it just me? http://info.chee.queensu.ca/chee440/chee440.htm

9. Tray Drying – Is it hot in here, or is it just me? Temperature - High Time - Long Cost – Low Capital, High operation Requires pre-drying steps currently employed to minimize moisture content

10. Freeze Drying – The Traditional Choice http://wine1.sb.fsu.edu/chm1045/notes/Forces/Phase/Forces06.htm

11. Freeze Drying – The Traditional Choice Freezing  This provides a necessary condition for low temperature drying. Vacuum  After freezing, the product is placed under vacuum. Heat  Heat is applied to the frozen product to accelerate sublimation. Condensation  Low-temperature condenser plates remove the vaporized solvent from the vacuum chamber by converting it back to a solid.

12. Freeze Drying – Equipment Selection Sizing based on SuperPro Insulin Simulation – Scale Up 15 kg of Insulin Crystal requires 40m 2 of drying area Allow 20% additional space 600 m 2 required for 190kg of product 15 o C, 24h typically used for protein drying

13. Freeze Drying – Product Concerns Stability  Long-term Moisture  Product is very hygroscopic Shelf life  Light, porous product Method of Delivery  Useful for re- suspension in sterile water for injection Cost  Expensive, long process

14. Spray Drying – The Next Challenge? Spray Drying – Basics  Fluid sprayed into air in droplets  Fluid evaporates, solid particle remains  Spherical, hollow (Like a gumball)

15. Spray Drying – The Next Challenge? http://info.chee.queensu.ca/chee440/chee440.htm

16. Spray Drying – The Next Challenge Stable, light product Inhalation? Temperature problems Cost  Expensive capital, low cost to operate

17. Which to choose? Freeze Drying – The Traditional Choice Spray Drying – The Next Challenge

18. References & Questions References CHEE 440 Website. http://info.chee.queensu.ca/chee440/chee440.htm (Amsden, 2004)http://info.chee.queensu.ca/chee440/chee440.htm Khachidze, D.G., Y.L Kalandadze, and J.R. Monaselidze. Microcalorimetric studies of insulin and Zn(II)-insulin over a wide range of pH and protein concentration. 2001. Phase Diagrams. http://wine1.sb.fsu.edu/chm1045/notes/Forces/Phase/Forces06.htm (Blaber, 1996.)http://wine1.sb.fsu.edu/chm1045/notes/Forces/Phase/Forces06.htm