Freeze Drying / Lyophilization of Pharmaceutical and Biological Products

Overview

Freeze drying, or lyophilization, is a well established technology used in the preservation of numerous pharmaceutical and biological products. This highly effective dehydration method involves the removal of water from frozen materials via the direct sublimation of ice. In recent years, this process has met with many changes, as have the regulations that impact lyophilization practices. This new edition of Freeze Drying/ Lyophilization of Pharmaceutical and Biological Products addresses these changes with updated and new chapters on emerging developments in lyophilization technology, research and industry procedures. Providing both a scientific and industrial perspective, this comprehensive text is a valuable resource for all those who use freeze drying technology.

Written by leading experts in the field, the third edition:

• Includes fundamental background on water and ice properties, phase transition of frozen liquids and the basics of freeze-drying techniques
• Analyzes the importance of product properties – looks at the challenges stemming from the increasing sensitivity of treated products
• Extensively covers formulation issues – looks at stabilizing additives and overall formulation characterization
• Emphasizes the growing significance of product container and closure interactions
• Describes some new up-front developments such as the coupling of lyophilization with irradiation
• Reviews new regulations and biological standards
• Introduces issues regarding manufacturing automation processes – specifically looks at Process Analytical Technology (PAT) and Quality by Design (QbD)

Contents

• FOREWORD
  Didier COULOMB - Director General of the International Institute of Refrigeration
• PREFACE

1. Fundamental issues and New Trends in Lyophilization - Louis REY
2. Structural and Dynamic Properties of Bulk and Confined Water - Jose TEIXEIRA and Marie-Claire Bellissent-Funel
3. Freezing and Annealing Phenomena in Lyophilization - Theodore RANDOLPH and James A. SEARLES
4. Phase Separation of Freeze-Dried Amorphous Solids : the Occurrence and Detection of Multiple Amorphous Phases in Pharmaceutical Systems - Adora M. PADILLA and Michael J. PIKAL
5. The use of microscopy, thermal analysis and impedance measurements to establish critical formulation parameters for freeze-drying cycle development - Kevin R. WARD and Paul MATEJTSCHUK
6. The relevance of the thermal properties for improving formulation and development : Application on freeze-drying of proteins and bacteria - Stéphanie PASSOT, Ion Cristian TRELEA, Michèle MARIN and Fernanda FONSECA
7. Freezing- and Drying- induced Perturbations of Protein Structure and Mechanisms of Protein Protection by Stabilizing Additives - John CARPENTER , Ken-ichi IZUTZU and Theodore W RANDOLPH
8. Mechanisms of Protein Stabilization During Freeze-Drying and Storage : the Relative Importance of Thermodynamic Stabilization and Glassy State Relaxation Dynamics - Michael J. PIKAL
9. Formulation Characterization - D.Q. WANG
10. Freeze-Drying with Non-Aqueous Co-Solvent systems - Dirk L. TEAGARDEN and David S. BAKER
11. Regulatory Control of Freeze-Dried Products : Importance of Residual Moisture - Joan C. MAY
12. Freeze-Drying of Biological Standards - Paul MATEJTSCHUK, Michelle ANDERSEN and Peter PHILIPS
13. Molecular Mobility of Freeze-Dried Formulations as Determined by NMR Relaxation and its effect on Storage Stability - Sumie YOSHIOKA and Yukio ASO
14. Electron Microscopy of Freeze-Dried Products - Tauno JALANTI
15. SCHOTT TopLyoTM - Optimized Vials For Lyophilization - Claudia DIETRICH, Matthias BICKER and Holger ROEHL
16. Closure and Container Consideration in Lyophilization - Frances L. DeGRAZIO
17. Extractables and Leachables as Container Considerations in Lyophilization - Frances L. DeGRAZIO and Diane PASKIET
18. Engineering Aspects of Freeze-Drying - James A. SEARLES
19. Monitoring and Control of Industrial Freeze-Drying Operations : The Challenge of implementing QbD (Quality-by-Design) - Miquel GALAN
20. Process Analytical Technology ( PAT ) in Industrial Freeze-Drying - Antonello BARRESI
21. Practical Considerations in Freeze-Drying in Syringes or Cartridges - Dirk L. TEAGARDEN, Stanley M. SPEAKER, Thomas OSTERBERG and Susan MARTIN
22. Lyophilization and Irradiation as an integrated Process – Florent KUNTZ

• INDEX