Lyophilization of Biopharmaceuticals

Henry R. Costantino, Ph.D. (Nastech Pharmaceutical) Michael J. Pikal, Ph.D. (University of Connecticut)

Preface Outlines

xi xv 1 3 43 75

Part 1
Freeze Dryers and the Fundamentals of Heatand Mass Transfer 1. Lyophilization Equipment Ed Trappler 2. Validation of Lyophilization: Equipment and Process Ed Trappler 3. Heat and Mass Transfer Issues in Freeze-drying Process Development Shailaja Rambhatla and Michael J. Pikal

Part 2
Process and Formulation Development and Product Characterization 4. Freeze-drying Process Development for Protein Pharmaceuticals Byeong S. Chang and Sugunakar Y. Patro 5. Excipients for Use in Lyophilized Pharmaceutical Peptide, Protein, and other Bioproducts Henry R. Costantino 6. The Role of Water in Physical Transformations in Freeze-dried Products Sheri L. Shamblin 7. Thermal Analysis of Lyophilized Pharmaceutical Peptide and Protein Formulations David Lechuga-Ballesteros, Danforth P. Miller, and Sarma P. Duddu 8. Microscopy of Lyophilized Proteins David E. Overcashier 111 113

139 229

271 337

Part 3
Physical Properties and Product Stability 9. Thermodynamics and Dynamics of Glassforming Systems C. A. Angell and J. L. Green 10. Physical Damage to Proteins During Freezing, Drying, and Rehydration John F. Carpenter, Byeong S. Chang, and Theodore W. Randolph 365 367 423

11. Degradation Pathways for Lyophilized Peptides and Proteins C. E. Stotz, S. L. Winslow, M. L. Houchin A. J. M. DSouza, J. Ji and E. M. Topp

443

Part 4
Non-traditional Freeze-drying Applications 481 12. Stabilization of Lyophilized Proteins Encapsulated in Controlled-release Polymers: Overview and Case Studies Including Formaldehyde-treated Vaccine Antigens 483 Wenlei Jiang, Henry R. Costantino, and Steven P. Schwendeman 13. Spray Freeze-drying of Biopharmaceuticals: Applications and Stability Considerations Yuh-Fun Maa and Henry R. Costantino 14. Freeze-drying of Liposomes: A Critical Review of Mechanisms Involved in Lyoprotection and Solid-state Stability Ewoud C.A. van Winden 15. Physical Stabilization of Plasmid DNA-based Therapeutics During Freezing and Drying Thomas J. Anchordoquy, Taylor K. Armstrong, Marion d.C. Molina, S. Dean Allison , Ye Zhang, Mayank M. Patel, Yvonne K. Lentz, and Gary S. Koe 16. Dehydrated Protein Powders as Biocatalysts in Nonaqueous Solvents Kai Griebenow and Gabriel Barletta Index 519

563

605

643 669