Freeze-Drying

Many modern medicines, for example blood derivatives, vaccines, cytostatic drugs, and antibiotics, but also soluble coffee, have one thing in common: freeze-drying is the best method of transforming the perishable substances into a form that keeps well and allows the substances to be stored before being returned almost to their natural state. This book describes the rules of freeze-drying. The critical process data is not just presented theoretically but explained with regard to practical examples. Application of freeze-drying processes is the main emphasis of this book. Many years of experience in the freeze-drying business allow the author to present valuable criteria for the selection of laboratory or industrial plants. Evaluation of the latest publications guarantees state-of-the-art coverage of information. Even modern topics, e.g., validation of processes or estimation of acceptable variances from preset values, are taken into account. These valuable tips make the book indispensable for everybody working in the freeze-drying business. Content: Chapter 1 Foundations and Process Engineering (pages 1–126): Chapter 2 Installation and Equipment Technique (pages 127–199): Chapter 3 Pharmaceutical, Biological and Medical Products (pages 201–238): Chapter 4 Food and Luxury Food (pages 239–248): Chapter 5 Metal Oxides, Ceramic?powders (pages 249–252): Chapter 6 Trouble Shooting and Regulatory Issues (pages 253–266): Freeze-Drying......Page 2 Contents......Page 10 1 Foundations and Process Engineering......Page 13 1.1.1 Amount of Heat, Heat Conductivity, Heat Transfer and Cooling Velocity......Page 14 1.1.2 Structure of Ice, Solutions and Dispersions......Page 24 1.1.3 Influence of Exipients: Growers of Structures and Cryoprotectant Agents (CPAs)......Page 32 1.1.4 Freezing of Cells and Bacteria......Page 39 1.1.5 Methods of Structure Analysis......Page 41 1.1.6 Changes of Structure in Freezing or Frozen Products......Page 69 1.2 Drying......Page 70 1.2.1 Main Drying (Sublimation Drying)......Page 72 1.2.2 Secondary Drying (Desorption Drying)......Page 89 1.2.3 Temperature and Pressure Measurement......Page 94 1.2.4 Water Vapor Transport during Drying......Page 110 1.2.5 Collapse and Recrystallization......Page 115 1.2.6 Drying Processes without Vacuum......Page 120 1.3 Storage......Page 121 I .3.1.1 Gravimetric Method......Page 122 1.3.1.2 Karl Fischer method......Page 123 1.3.1.4 Infra-red Spectroscopy......Page 124 1.3.2 Influence of Vial Stoppers on the Residual Moisture Content......Page 127 1.3.3 Qualities of the Dry Substances and their Changes......Page 128 2.1.1 Cooling by Liquids: Shell-Freezing and Spin-Freezing......Page 139 2.1.2 Cooled Surfaces......Page 140 2. I .3 Product in the Flow of Cold Air, Foaming and Freezing of Extracts and Pulps......Page 141 2.1.4 Droplet Freezing in Cold Liquids......Page 144 2.2.1 Installations for Flasks and Manifolds......Page 145 2.2.2 Drying Chambers and Forms of Trays......Page 147 2.2.3 Shelves and their Cooling and Heating......Page 153 2.2.4 Water Vapor Condensers......Page 154 2.2.5 Refrigerating Systems and Refrigerants......Page 160 2.2.6 Vacuum Pumps......Page 166 2.2.8 Measuring and Control Systems......Page 170 2.3.1 Universal Laboratory Plants......Page 185 2.3.2 Pilot Plants......Page 187 2.3.3 Manipulators and Stoppering Systems for Vials......Page 189 2.3.4 Cleaning Installations, Sterilization by Steam and VHP......Page 191 2.4 Chamber Production Plants......Page 196 2.4.1 Loading and Unloading Systems......Page 200 2.5.1 Discontinuous Plants......Page 203 2.5.2 Continuos Plants with Tray Transport......Page 204 2.5.3 Continuous Plants with Product Transport by Wipers or by Vibration......Page 207 3.1 Proteins and Hormones......Page 213 3.2 Viruses, Vaccines, Bacteria, and Yeasts......Page 224 3.3 Antibiotics, Cytostatics and Ibuprofen......Page 230 3.4 Liposomes and Nanoparticles......Page 231 3.5 Transplants......Page 239 4 Food and Luxury Food......Page 251 4.1 Vegetables, Potatoes, Fruits and Juices......Page 254 4.2 Coffee......Page 256 4.3 Eggs, Rice......Page 259 5 Metal Oxides, Ceramic-powders......Page 261 6.1.1 Prolonged Evacuation Time......Page 265 6.1.4 Slow Pressure Increase in the Chamber During Main Drying......Page 266 6.1.6 Traces of Highly Volatile Solvents (Acetone, Ethanol)......Page 267 6.1.7 Different Structure of the Dried Product in the Center and Border of a Shelf......Page 268 6.2 Qualification and Validation of Processes and Installations......Page 269 6.2.1 Quality of the Product......Page 270 6.2.2 Description of the Process Developed for Manufacture of the Product......Page 271 6.2.3 Description of Production Installations and their Handling......Page 273 6.2.4 Equipment Performance Tests......Page 274 6.2.5 Quality of Installation to Document the Ability of Equipment to Operate Processes (described in Section 6.2.2)......Page 276 6.2.6 Documentation of the Quality of the Products Manufactured (in comparison with 6.2.1)......Page 278 Appendix......Page 279 Index......Page 283 Many modern medicines, such as blood derivatives, vaccines, cytostatic drugs, and antibiotics and also soluble coffee, have one thing in common: freeze-drying. This text describes the rules of freeze-drying and focuses on the application of freeze-drying. Many modern medicines such as blood derivatives, vaccines and antibiotics are freeze-dried. This is considered the best method of transforming the perishable substances into a form that keeps well. This book describes the rules of freeze-drying Freeze-drying or lyophilization is a drying process in which the solvent and/or the suspension medium is crystallized at low temperatures and thereafter sublimed from the solid state directly into the vapor phase.