08014nam 2200625Ia 450 991081340010332120200520144314.01-84755-770-8(CKB)2670000000276250(EBL)1185544(SSID)ssj0000755768(PQKBManifestationID)11440209(PQKBTitleCode)TC0000755768(PQKBWorkID)10732643(PQKB)11735080(MiAaPQ)EBC1185544(Au-PeEL)EBL1185544(CaPaEBR)ebr10618749(CaONFJC)MIL871916(OCoLC)232639136(PPN)19846777X(EXLCZ)99267000000027625020080204d2007 uy 0engur|n|---|||||txtrdacontentcrdamediacrrdacarrierFreeze-drying of pharmaceuticals and biopharmaceuticals [principles and practice] /Felix Franks ; in association with Tony Auffret1st ed.Cambridge RSC Publishingc20071 online resource (xii, 206 pages) illustrationsDescription based upon print version of record.0-85404-151-6 Includes bibliographical references (p. 190-200) and index.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.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.Frozen drugsFreeze-dryingBiopharmaceuticsFrozen drugs.Freeze-drying.Biopharmaceutics.615.18Franks Felix18323Auffret Tony1604877MiAaPQMiAaPQMiAaPQBOOK9910813400103321Freeze-drying of pharmaceuticals and biopharmaceuticals3929861UNINA