Freeze-drying of pharmaceuticals and biopharmaceuticals : [principles and practice] / Felix Franks ; in association with Tony Auffret.

Format:

Book

Author/Creator:

Franks, Felix.

Contributor:

Auffret, Tony.

Language:

English

Subjects (All):

Frozen drugs.

Freeze-drying.

Biopharmaceutics.

Physical Description:

1 online resource (xii, 206 pages) : illustrations

Edition:

1st ed.

Place of Publication:

Cambridge : RSC Publishing, c2007.

Language Note:

English

Summary:

Freeze-drying, in the past popular in the food industry, has more recently been adopted by the pharmaceutical industry as a standard method for the production of stable solid preparations. Freeze-drying of Pharmaceuticals and Biopharmaceuticals is the first book to specifically describe this process, as related to the pharmaceutical industry. The emphasis of this book is on the properties of the materials processed, how effective formulations are arrived at, and how they are stored and marketed. Beginning with a historical overview of the process, Freeze-drying of Pharmaceuticals and Biopharmaceuticals briefly describes the processes and equipment involved, including: the physics, chemistry and biochemistry associated with freezing, aspects of formulation development, primary and secondary drying; the economics and engineering of scaling up; and, most importantly, attributes of the dried product. It also discusses in detail the science behind freeze-drying, such as the properties of crystalline and amorphous solids. The book concludes with selected case studies and discusses the future of freeze-drying, advances in alternative drying methods, and concludes with an extensive bibliography. This book, written by a leading expert in the field, is aimed primarily at product and process developers in the biopharmaceutical industry and academia.

Contents:

Freeze-Drying of Pharmaceuticals and Biopharmaceuticals

Contents

Chapter 1 Historical Background

1.1 History of Drying as a Preservation Method

1.2 Advent of Industrial Freeze-Drying

1.3 Elements of Stability

1.4 Why Freeze-Dry?

1.5 Stability: The Downside

Chapter 2 The Process Sequence in Summary

2.1 Equipment

2.2 Drying Process: Coupled Heat and Mass Transfer

2.3 How Dry Is "Dry"?

2.4 Why Not Freeze-Dry?

Chapter 3 Essential Product and Process Parameters in Summary

3.1 General Considerations

3.2 Formulation Parameters

3.3 Process Parameters

3.4 Multidisciplinary Nature of Freeze-Drying

3.5 Conclusions

Chapter 4 Essential Physics of Low Temperature and Freezing

4.1 Chill Versus Freezing: Undercooling

4.2 Deep Chill: Undercooled Water

4.3 Physical Properties of Undercooled Water

4.4 Ice: Its Nucleation in Undercooled Water

4.5 Ice: Crystallisation and Crystal Habits

4.6 Nucleation and Crystallisation of Ice and Solutes in Aqueous Solutions

4.7 Polymorphic Transitions, Hydrates and Transient Hydrates

4.8 Vitrification as Avoidance of Crystallisation

4.9 Freeze-Drying of Complex Biological Materials

Chapter 5 Essential Chemistry and Biochemistry Associated with Low Temperature and Freezing

5.1 Physicochemical Properties of Water-Based Systems under Conditions of Deep Chill

5.2 Cold Inactivation of Proteins

5.3 Changing Phase Relationships during Freezing

5.4 Eutectic Crystallisation of pH Buffer Components

5.5 Effects of Freeze-Concentration on Reaction Kinetics

5.6 Complex Ternary and Multicomponent Phase Behaviour

5.7 Supersaturation and Vitrification: The Importance of the State Diagram

5.8 Aqueous Glasses as Solid Solutions

Chapter 6 Physical Properties of Crystalline and Amorphous Solids.

6.1 Crystalline and Amorphous Solids: A Comparison

6.2 Non-Equilibrium Processes in Amorphous Solids

6.3 Slow Relaxation during Cooling and Heating

6.4 Glass Transition: A Summary

6.5 Amorphous States and Freezing Behaviour

6.6 Materials Science of the Glass Transition: Its Relevance to Freeze-Drying

Chapter 7 Excipients: Their Role in Rational Formulation Design

7.1 Definitions and Classifications

7.2 Attributes and Requirements

7.3 Estimation of Tg of Complex Mixtures

7.4 Effects of Excipients on Product Attributes

7.5 Implications for Freeze-Drying

7.6 Devitrification of Excipients in Dried Amorphous Preparations

7.7 Pharmaceutical Glasses: Formulation Aspects

7.8 Constraints

7.9 Operational Degrees of Freedom

Chapter 8 Primary Drying: The Sublimation of Ice

8.1 Principles of Coupled Heat and Mass Transfer

8.2 Model

8.3 Heat Transfer Mechanisms

8.4 Influences of Formulation and Freezing Procedure on Ice Sublimation

8.5 Interplay of Pressure, Temperature and Time

8.6 Adjustable Parameters: Formulation, Concentration and Fill Depth

8.7 Ideal Conditions

8.8 Accelerated Freeze-Drying

8.9 Monitoring Ice Sublimation

8.10 Summary

Chapter 9 Secondary Drying: The Removal of Unfrozen Water

9.1 Unfrozen (Residual) Water

9.2 Removal of Unfrozen Water by Diffusion

9.3 Effects of Pressure

9.4 Effect of Water Content

9.5 Effects of Fill Depth and Cake Morphology

9.6 Effect of Temperature

9.7 Softening and Collapse

9.8 Operational Drying Protocols: Temperature Ramping and Stepwise Heating

Chapter 10 Some Practical Aspects

10.1 Scale-Up and ICH Manufacture

10.2 Economics

10.3 Vial Closure and Packaging

10.4 Process Monitoring and Control

10.5 Stability Issues

Chapter 11 The Dried Product

11.1 Physical State: Crystalline or Amorphous?.

11.2 Essential Materials Science of Crystalline and Amorphous Products

11.3 Essentials of Thermoanalytical Techniques

11.4 Fragility and Its Estimation

11.5 Monitoring Physical and Chemical Stability

11.6 Estimation of Useful Shelf Life

11.7 Dynamics in Supersaturated Solutions

11.8 Residual Water and Its Estimation

11.9 Residual Water: Its Influence on Stability

11.10 Unresolved Issues

11.11 Reconstitution at Point of Administration

Chapter 12 Case Histories

12.1 Introduction

12.2 Choice of Formulation

12.3 Process Cycle Optimisation

12.4 Concurrent Product and Process Refinement

12.5 Inadvertent Failures: "Unexpected Problems"

12.6 Unfamiliarity with Freeze-Drying Parameters

12.7 In situ Water Release during Storage

12.8 Summary and Conclusions

Chapter 13 Beyond Freeze-Drying

13.1 Alternative Water Removal Technologies

13.2 Evaporative Drying: Principles and Practice

13.3 Evaporative Drying: The Current State

13.4 Comparisons with Freeze-Drying

Acknowledgements

Bibliography

Subject Index.

Notes:

Description based upon print version of record.

Includes bibliographical references (p. 190-200) and index.

ISBN:

9781847557704

1847557708

OCLC:

232639136