The moisture content within a freeze dried material has a direct effect on the glass transition (Tg) of the material.
Moisture content across a shelf or batch may vary, causing discrepencies or even stability issues.
Use Of Freeze Drying Microscopy To Determine Critical ParametersBTL
Freeze-drying microscopy (FDM) allows observation of materials during freeze-drying at the microscopic level. FDM can determine critical parameters like collapse temperature and eutectic temperature prior to lyophilization. It does this by observing changes in sample structure as the temperature is varied, such as when the sample collapses or melts. FDM provides visual information on various freeze-drying phenomena that can be useful for formulation and process development.
Alternatives To Lyophilization Visiongain Lyo SearlesJim Searles
1. The document discusses alternatives to lyophilization for drying pharmaceuticals and biologics, including spray drying, bubble drying, spray-freeze drying, stirred freeze drying, and foam drying.
2. It provides details on various drying processes and technologies such as Aktiv-Dry bubble drying and Niro spray drying systems. Case studies are presented on drying different materials like vaccines, antibodies, and insulin using these alternative methods.
3. Comparative results from studies drying live virus vaccines and monoclonal antibodies using lyophilization, spray drying, and foam drying are described, showing in some cases alternatives like foam drying produced more stable products.
Lyophilization, also known as freeze drying, is a process used to preserve thermolabile materials such as pharmaceuticals and food by removing water from the materials after they are frozen. The process involves freezing the material, reducing pressure to allow the frozen water to sublimate directly from the solid phase to gas phase, and then using low temperatures and pressure to remove remaining water. Freeze drying allows heat-sensitive materials to be dried without significant damage and results in a material that can be stored without refrigeration and reconstituted by adding water. Common applications of lyophilization include preserving vaccines, plasma, bacteria, and thermolabile pharmaceuticals to extend their shelf life.
This document discusses different types of solids found in environmental samples and their measurement. It defines total solids, total suspended solids, total dissolved solids, volatile solids, and fixed solids. Key points include: total solids are all solids in a sample, total suspended solids are filterable, total dissolved solids pass through a filter, and volatile solids are lost during ignition while fixed solids remain. The document provides methods for measuring total suspended solids, including filtration, drying, ignition, and calculations. It also discusses the environmental significance of different solids measurements.
Lyophilization, also known as freeze drying, is a process that removes water from a material through sublimation while preserving its structure and composition. It works by first freezing the material and then reducing the pressure and increasing the temperature to allow the frozen water to change directly from solid to gas without passing through the liquid phase. A simple lyophilizer freezes materials on heated shelves, lowers the chamber pressure to 0.06 atmospheres using a vacuum pump, causing the frozen water to sublimate into a gas and condense on a freezing coil outside the chamber. Lyophilization is used to preserve bacterial and viral cultures, dry numerous products, and store water-damaged materials like manuscripts.
Freeze drying, also known as lyophilization, is a process used to preserve thermolabile materials such as foods, biological products, and pharmaceuticals. It works by freezing the material and then reducing the pressure and adding heat to allow the frozen solvent, such as water, to sublimate from the solid phase to gas phase without passing through the liquid phase. The process involves three main stages - freezing, primary drying where sublimation occurs, and secondary drying where remaining bound water is removed. Freeze drying preserves materials by removing water while retaining the material's structure, allowing heat-sensitive substances to be dried and stored without refrigeration.
The moisture content within a freeze dried material has a direct effect on the glass transition (Tg) of the material.
Moisture content across a shelf or batch may vary, causing discrepencies or even stability issues.
Use Of Freeze Drying Microscopy To Determine Critical ParametersBTL
Freeze-drying microscopy (FDM) allows observation of materials during freeze-drying at the microscopic level. FDM can determine critical parameters like collapse temperature and eutectic temperature prior to lyophilization. It does this by observing changes in sample structure as the temperature is varied, such as when the sample collapses or melts. FDM provides visual information on various freeze-drying phenomena that can be useful for formulation and process development.
Alternatives To Lyophilization Visiongain Lyo SearlesJim Searles
1. The document discusses alternatives to lyophilization for drying pharmaceuticals and biologics, including spray drying, bubble drying, spray-freeze drying, stirred freeze drying, and foam drying.
2. It provides details on various drying processes and technologies such as Aktiv-Dry bubble drying and Niro spray drying systems. Case studies are presented on drying different materials like vaccines, antibodies, and insulin using these alternative methods.
3. Comparative results from studies drying live virus vaccines and monoclonal antibodies using lyophilization, spray drying, and foam drying are described, showing in some cases alternatives like foam drying produced more stable products.
Lyophilization, also known as freeze drying, is a process used to preserve thermolabile materials such as pharmaceuticals and food by removing water from the materials after they are frozen. The process involves freezing the material, reducing pressure to allow the frozen water to sublimate directly from the solid phase to gas phase, and then using low temperatures and pressure to remove remaining water. Freeze drying allows heat-sensitive materials to be dried without significant damage and results in a material that can be stored without refrigeration and reconstituted by adding water. Common applications of lyophilization include preserving vaccines, plasma, bacteria, and thermolabile pharmaceuticals to extend their shelf life.
This document discusses different types of solids found in environmental samples and their measurement. It defines total solids, total suspended solids, total dissolved solids, volatile solids, and fixed solids. Key points include: total solids are all solids in a sample, total suspended solids are filterable, total dissolved solids pass through a filter, and volatile solids are lost during ignition while fixed solids remain. The document provides methods for measuring total suspended solids, including filtration, drying, ignition, and calculations. It also discusses the environmental significance of different solids measurements.
Lyophilization, also known as freeze drying, is a process that removes water from a material through sublimation while preserving its structure and composition. It works by first freezing the material and then reducing the pressure and increasing the temperature to allow the frozen water to change directly from solid to gas without passing through the liquid phase. A simple lyophilizer freezes materials on heated shelves, lowers the chamber pressure to 0.06 atmospheres using a vacuum pump, causing the frozen water to sublimate into a gas and condense on a freezing coil outside the chamber. Lyophilization is used to preserve bacterial and viral cultures, dry numerous products, and store water-damaged materials like manuscripts.
Freeze drying, also known as lyophilization, is a process used to preserve thermolabile materials such as foods, biological products, and pharmaceuticals. It works by freezing the material and then reducing the pressure and adding heat to allow the frozen solvent, such as water, to sublimate from the solid phase to gas phase without passing through the liquid phase. The process involves three main stages - freezing, primary drying where sublimation occurs, and secondary drying where remaining bound water is removed. Freeze drying preserves materials by removing water while retaining the material's structure, allowing heat-sensitive substances to be dried and stored without refrigeration.
Lyophilization, or freeze drying, is a process used to preserve thermolabile pharmaceutical products and biological materials. It works by freezing the product and then reducing pressure to allow the frozen water in the product to sublime from a solid to gas without passing through the liquid phase. This allows heat-sensitive materials to be dried without excessive heat damage. The process involves freezing the product, primary drying where ice is removed by sublimation under vacuum, and secondary drying where remaining bound water is removed by desorption. Freeze drying is useful for preserving materials like vaccines, blood products, enzymes and other biologics as it prevents degradation and improves stability at low temperatures.
This document discusses film formation in coatings. The most important step in any coating process is the conversion of the coating from liquid to solid through film formation behavior and polymer glass transition temperature, which significantly impact the properties of a polymer. Thermoplastic coatings such as polyethylene and polypropylene melt on heating and re-solidify on cooling. The glass transition temperature is the temperature at which an amorphous polymer transitions between rubbery and glassy states, constituting an important mechanical property. Common coating techniques include dip coating, spraying, rolling, and spin coating.
A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions
1. Film formation is the process by which a liquid coating is converted into a solid film after application. There are two main mechanisms for this - solvent evaporation and chemical crosslinking reactions.
2. For thermoplastic coatings, film formation occurs as the solvent evaporates, causing an increase in the glass transition temperature (Tg) of the coating to match or exceed the ambient temperature. For crosslinking coatings, particles soften and coalesce during heating, then chemical reactions cause molecular weight and viscosity to increase until the surface sets.
3. Both types of coatings aim to overcome issues like solvent retention, shrinkage stresses, and environmental pollution, though crosslinking systems are more thermally and chemically
Every freeze-drying formulation has a critical temperature. During primary drying the formulation must be kept below this temperature in order to prevent processing defects or complete collapse. Improperly dried products will exhibit reduced levels of activity, decreased solubility, and poor stability - even if they do not look any different.
Freeze drying microscopy enables critical temperatures such as collapse, melting and freezing point to be quickly and easily identified with as little 2ml of the formulation. With this information freeze drying cycles can be designed that are efficient, robust and safe for your product.
Definition of drying
Importance of drying
Difference between drying and evaporation
Equipments
References
Definition
A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions.
History
Freeze drying was first actively developed during WORLD WAR II transport of serum.
The main aim was to store the products without refrigeration and to remove moisture from thermolabile compounds.
Atlas in 1961 built 6 production freeze drying cabinet for Nestle group in Germany, Holland.
Principle
Lyophilization is carried out using a simple principle of physics sublimation. Sublimation is the transition of a substance from the solid to the vapour state, without first passing through an intermediate liquid phase.
Lyophilization is performed at temperature and pressure conditions below the triple point, to enable sublimation of ice.
The entire process is performed at low temperature and pressure by applying vacuum, hence is suited for drying of thermolabile compounds.
The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during lyophilization.
This document discusses different types of solids found in water samples:
- Total Suspended Solids (TSS) are solids that can be filtered from water. Samples are filtered and weighed to determine TSS concentration.
- Total Dissolved Solids (TDS) pass through filters and remain dissolved in water. Samples are filtered, dried, and weighed to measure TDS.
- Volatile Suspended Solids (VSS) are organic solids that are lost upon ignition. Heating samples provides a rough estimate of organic matter.
- Total Solids (TS) is the total of all solids, including TSS, TDS, and VSS. Proced
General consideration for process design of lyophilized productRajeev Sharma
Lyophilization is commonly used to improve stability and shelf life of injectable drugs like proteins, peptides, and liposomes. It involves three steps: freezing, primary drying where ice sublimates under vacuum, and secondary drying to remove bound water. Key considerations for lyophilization process design include excipient selection, filling container and closure system selection, pre-formulation studies, and ensuring the reconstituted product is suitable for injection. Process parameters like freezing rate and temperature, drying temperature and vacuum level must be optimized. Quality attributes of the lyophilized cake and reconstituted drug product are monitored through analytical testing and stability studies.
This experiment determined various solids concentrations in water samples to assess water quality. Three water samples - tap water, surface water, and mixed water - were tested. Parameters like total solids (TS), total volatile solids (TVS), total fixed solids (TFS), total suspended solids (TSS), fixed suspended solids (FSS), total dissolved solids (TDS), and total volatile dissolved solids (TVDS) were measured using techniques like weighing, filtration, evaporation at 105°C, and combustion at 550°C. The results showed that surface water had the highest solids concentrations, while tap water had the lowest as it was
The document discusses extrusion technology, which is a process used to embed drugs in polymeric carriers or convert raw materials into products of uniform shape and density by forcing them through a die. Extrusion has several advantages, including enhancing bioavailability of poorly soluble drugs and allowing for sustained, modified, and targeted drug release. The process involves using active ingredients, polymers, plasticizers and other processing aids which are fed into an extruder containing a screw-barrel assembly, die assembly, and vacuum assembly. The extrudates are then evaluated using techniques like DSC, TGA, XRD, and microscopy to characterize properties like thermal behavior and crystallinity. Finally, extrusion has applications in masking bitter drug tastes, increasing drug solub
This document provides an overview of the freeze drying (lyophilization) process. It discusses the three main steps: freezing, primary drying, and secondary drying. Freezing involves cooling the material below its freezing point. Primary drying occurs under vacuum where water sublimates from the frozen material. Secondary drying removes unfrozen water under higher temperature and lower pressure. The document also describes the components and working of freeze drying equipment, including the refrigeration system, vacuum system, product chamber, and condenser. Common excipients used in lyophilized formulations are discussed, such as bulking agents, stabilizers, and buffers.
Preservation of Probiotic Bacteria by Freeze-Drying, and Achieving Stomach an...BTL
Preservation of Probiotic Bacteria by Freeze-Drying, and Achieving Stomach and Bile Acid Resistance: A TSB-funded research project by BTL, Microbial Development Ltd and the University of Cambridge.
Industrial pharmacy is a discipline which includes manufacturing, development, marketing and distribution of drug products including quality assurance of these activities
The reasons for the increasing of large scale manufacturing
Economic – As the scale of manufacturing batches increases so, proportionally, does the cost of production decreases
Accuracy – The larger the quantities of materials involved so, proportionally, is the accuracy of measurements increased
Greater scope – The increasing complexity of modern therapy has made it virtually impossible to prepare many medicaments on a small scale
Determination of Total Solids in Biomass and Total Dissolved Solids in Liquid...BiorefineryEPC™
Determination of Total Solids in Biomass and Total Dissolved Solids in Liquid Process Samples
YOU AGREE TO INDEMNIFY BiorefineryEPCTM , AND ITS AFFILIATES, OFFICERS, AGENTS, AND EMPLOYEES AGAINST ANY CLAIM OR DEMAND, INCLUDING REASONABLE ATTORNEYS' FEES, RELATED TO YOUR USE, RELIANCE, OR ADOPTION OF THE DATA FOR ANY PURPOSE WHATSOEVER. THE DATA ARE PROVIDED BY BiorefineryEPCTM "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY DISCLAIMED. IN NO EVENT SHALL BiorefineryEPCTM BE LIABLE FOR ANY SPECIAL, INDIRECT OR CONSEQUENTIAL DAMAGES OR ANY DAMAGES WHATSOEVER, INCLUDING BUT NOT LIMITED TO CLAIMS ASSOCIATED WITH THE LOSS OF DATA OR PROFITS, WHICH MAY RESULT FROM ANY ACTION IN CONTRACT, NEGLIGENCE OR OTHER TORTIOUS CLAIM THAT ARISES OUT OF OR IN CONNECTION WITH THE USE OR PERFORMANCE OF THE DATA.
This document provides an overview of freezing technology and the current status of frozen products in India. It discusses the history and development of freezing, defines key freezing terms, and describes the freezing process and factors that affect it. It also outlines different freezing methods like air freezing, contact freezing, and cryogenic freezing. The document concludes with advantages and disadvantages of freezing and statistics on India's frozen product industry which shows increasing production volumes and values from 2015-2018.
This document describes methods for determining the moisture content of crude drugs, including loss on drying and azeotropic distillation. Loss on drying is the common gravimetric method, which involves weighing a sample before and after drying in an oven at 100°C until the weight is constant. Azeotropic distillation is a volumetric method that uses toluene to distill any water in a sample into a graduated tube, allowing the volume of water to be measured and moisture content calculated based on the sample weight. Other instrumental methods like gas chromatography and NMR are also mentioned. The key steps of each technique are outlined.
Sublimation is a purification process where a solid transitions directly to its gas phase without passing through a liquid phase. It involves precise control of individual purification steps under vacuum or gas flow conditions. Sublimation is commonly used to purify pharmaceuticals and can also be used to create freeze-dried substances or porous drug tablets using a sublimating material like camphor. Another application is sublimating dye onto fabrics to create designs without affecting the fabric's feel or performance.
Lyotherm2: Thermal Analyses for Freeze Drying CharacterisationBTL
Lyotherm is a novel analytical instrument that combines DTA and Impedance Analysis to provide a thorough understanding of a product's freeze drying characteristics.
The document discusses a study that evaluated the impact of controlled nucleation on primary drying time during freeze drying. Two solutions of 5% sucrose were prepared, one with controlled nucleation at -3°C using ControLyo technology, and one without control that nucleated randomly down to -17°C. Primary drying times were determined using a Pirani/capacitance manometer differential. Controlled nucleation led to uniform nucleation of all vials at once and resulted in a primary drying time of 30.5 hours, compared to 40.4 hours for uncontrolled nucleation, a savings of 10 hours or 24%.
EXPERIMENT 8 PRECIPITATION HARDENING IN 2024 ALUMINUM .docxSANSKAR20
EXPERIMENT 8
PRECIPITATION HARDENING IN 2024 ALUMINUM
Objective
To study the time and temperature variations in the hardness of Al-4% Cu alloy on
isothermal aging.
Introduction
Materials can be hardened by inhibiting the motion of crystal defects called dislocations. In
pure metals, the presence of defects (such as vacancies, interstitials, dislocations and grain
boundaries) can enhance the strength. In single phase alloys, additional resistance to
deformation may arise from the presence of foreign atoms. In two-phase alloys, additional
stress is needed to enable the dislocation to intersect the second-phase particles. A finely
dispersed precipitate may, therefore, strengthen the material. This phenomenon is termed
precipitation hardening.
The thermodynamics of precipitation in 2024 Al can best be understood by referring to the
binary phase diagram of Aluminum-Copper in the aluminum-rich region in Figure 8-1.
When the aluminum-copper alloy of less than 5 wt% copper is heated to a temperature just
above the solvus line, only one phase (kappa, ) is thermodynamically stable. Other solid
phases dissolve (disappear). This process is called solution treatment. The only requirement
is that the specimen must be kept at this temperature for a long enough time. To solution
treat a sample of 2024 Al (4 wt% Cu), the sample should be heated to 930°F (500°C) and held
for 30 minutes.
When a solution treated sample is rapidly cooled (quenched) to below the solvus line (Figure
8-1), two phases are thermodynamically stable (kappa and theta). These phases are two
different solids, physically distinct, and separated by a phase boundary. The process is
similar to precipitation of salt in supersaturated brine.
The process of precipitation is not instantaneous, as is often the case in liquid-solid
precipitation. The process involves the formation of embryos of theta through thermal
fluctuations and their subsequent growth, once they achieve stability. With time, more and
more precipitates form. This process is called aging. Once the solution achieves an
equilibrium composition given by the solvus line for the aging temperature, precipitation
stops. For example, the precipitation of the copper-rich theta phase depletes the kappa phase
of copper to approximately 1-1/2 wt% Cu at 715°F (380°C).
The distribution of precipitates affects the hardness and yield strength. The hardness and
yield strength are greater when the precipitates are small and finely dispersed in the kappa
matrix than when the precipitates are large and not finely scattered. Therefore, to gain
hardness in 2024 Al, the specimen should be heat treated to produce a fine dispersion of
small precipitates.
Unfortunately, there is a tendency when thermodynamic equilibrium is reached for large
precipitates to grow and small precipitates to shrink. This will lower the surface to volume
ratio of the precip ...
Borosilicate glass has unique chemical and physical properties that make it well-suited for use in the chemical, food, pharmaceutical, and other industries. It has outstanding corrosion resistance, is transparent and inert. Borosilicate glass can withstand high temperatures up to 250°C and pressures depending on the component size. It also has low thermal expansion, is electrically insulating, and can be combined with other materials like PTFE. Borosilicate glass 3.3 is commonly used for its balance of properties.
Lyophilization, or freeze drying, is a process used to preserve thermolabile pharmaceutical products and biological materials. It works by freezing the product and then reducing pressure to allow the frozen water in the product to sublime from a solid to gas without passing through the liquid phase. This allows heat-sensitive materials to be dried without excessive heat damage. The process involves freezing the product, primary drying where ice is removed by sublimation under vacuum, and secondary drying where remaining bound water is removed by desorption. Freeze drying is useful for preserving materials like vaccines, blood products, enzymes and other biologics as it prevents degradation and improves stability at low temperatures.
This document discusses film formation in coatings. The most important step in any coating process is the conversion of the coating from liquid to solid through film formation behavior and polymer glass transition temperature, which significantly impact the properties of a polymer. Thermoplastic coatings such as polyethylene and polypropylene melt on heating and re-solidify on cooling. The glass transition temperature is the temperature at which an amorphous polymer transitions between rubbery and glassy states, constituting an important mechanical property. Common coating techniques include dip coating, spraying, rolling, and spin coating.
A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions
1. Film formation is the process by which a liquid coating is converted into a solid film after application. There are two main mechanisms for this - solvent evaporation and chemical crosslinking reactions.
2. For thermoplastic coatings, film formation occurs as the solvent evaporates, causing an increase in the glass transition temperature (Tg) of the coating to match or exceed the ambient temperature. For crosslinking coatings, particles soften and coalesce during heating, then chemical reactions cause molecular weight and viscosity to increase until the surface sets.
3. Both types of coatings aim to overcome issues like solvent retention, shrinkage stresses, and environmental pollution, though crosslinking systems are more thermally and chemically
Every freeze-drying formulation has a critical temperature. During primary drying the formulation must be kept below this temperature in order to prevent processing defects or complete collapse. Improperly dried products will exhibit reduced levels of activity, decreased solubility, and poor stability - even if they do not look any different.
Freeze drying microscopy enables critical temperatures such as collapse, melting and freezing point to be quickly and easily identified with as little 2ml of the formulation. With this information freeze drying cycles can be designed that are efficient, robust and safe for your product.
Definition of drying
Importance of drying
Difference between drying and evaporation
Equipments
References
Definition
A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions.
History
Freeze drying was first actively developed during WORLD WAR II transport of serum.
The main aim was to store the products without refrigeration and to remove moisture from thermolabile compounds.
Atlas in 1961 built 6 production freeze drying cabinet for Nestle group in Germany, Holland.
Principle
Lyophilization is carried out using a simple principle of physics sublimation. Sublimation is the transition of a substance from the solid to the vapour state, without first passing through an intermediate liquid phase.
Lyophilization is performed at temperature and pressure conditions below the triple point, to enable sublimation of ice.
The entire process is performed at low temperature and pressure by applying vacuum, hence is suited for drying of thermolabile compounds.
The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during lyophilization.
This document discusses different types of solids found in water samples:
- Total Suspended Solids (TSS) are solids that can be filtered from water. Samples are filtered and weighed to determine TSS concentration.
- Total Dissolved Solids (TDS) pass through filters and remain dissolved in water. Samples are filtered, dried, and weighed to measure TDS.
- Volatile Suspended Solids (VSS) are organic solids that are lost upon ignition. Heating samples provides a rough estimate of organic matter.
- Total Solids (TS) is the total of all solids, including TSS, TDS, and VSS. Proced
General consideration for process design of lyophilized productRajeev Sharma
Lyophilization is commonly used to improve stability and shelf life of injectable drugs like proteins, peptides, and liposomes. It involves three steps: freezing, primary drying where ice sublimates under vacuum, and secondary drying to remove bound water. Key considerations for lyophilization process design include excipient selection, filling container and closure system selection, pre-formulation studies, and ensuring the reconstituted product is suitable for injection. Process parameters like freezing rate and temperature, drying temperature and vacuum level must be optimized. Quality attributes of the lyophilized cake and reconstituted drug product are monitored through analytical testing and stability studies.
This experiment determined various solids concentrations in water samples to assess water quality. Three water samples - tap water, surface water, and mixed water - were tested. Parameters like total solids (TS), total volatile solids (TVS), total fixed solids (TFS), total suspended solids (TSS), fixed suspended solids (FSS), total dissolved solids (TDS), and total volatile dissolved solids (TVDS) were measured using techniques like weighing, filtration, evaporation at 105°C, and combustion at 550°C. The results showed that surface water had the highest solids concentrations, while tap water had the lowest as it was
The document discusses extrusion technology, which is a process used to embed drugs in polymeric carriers or convert raw materials into products of uniform shape and density by forcing them through a die. Extrusion has several advantages, including enhancing bioavailability of poorly soluble drugs and allowing for sustained, modified, and targeted drug release. The process involves using active ingredients, polymers, plasticizers and other processing aids which are fed into an extruder containing a screw-barrel assembly, die assembly, and vacuum assembly. The extrudates are then evaluated using techniques like DSC, TGA, XRD, and microscopy to characterize properties like thermal behavior and crystallinity. Finally, extrusion has applications in masking bitter drug tastes, increasing drug solub
This document provides an overview of the freeze drying (lyophilization) process. It discusses the three main steps: freezing, primary drying, and secondary drying. Freezing involves cooling the material below its freezing point. Primary drying occurs under vacuum where water sublimates from the frozen material. Secondary drying removes unfrozen water under higher temperature and lower pressure. The document also describes the components and working of freeze drying equipment, including the refrigeration system, vacuum system, product chamber, and condenser. Common excipients used in lyophilized formulations are discussed, such as bulking agents, stabilizers, and buffers.
Preservation of Probiotic Bacteria by Freeze-Drying, and Achieving Stomach an...BTL
Preservation of Probiotic Bacteria by Freeze-Drying, and Achieving Stomach and Bile Acid Resistance: A TSB-funded research project by BTL, Microbial Development Ltd and the University of Cambridge.
Industrial pharmacy is a discipline which includes manufacturing, development, marketing and distribution of drug products including quality assurance of these activities
The reasons for the increasing of large scale manufacturing
Economic – As the scale of manufacturing batches increases so, proportionally, does the cost of production decreases
Accuracy – The larger the quantities of materials involved so, proportionally, is the accuracy of measurements increased
Greater scope – The increasing complexity of modern therapy has made it virtually impossible to prepare many medicaments on a small scale
Determination of Total Solids in Biomass and Total Dissolved Solids in Liquid...BiorefineryEPC™
Determination of Total Solids in Biomass and Total Dissolved Solids in Liquid Process Samples
YOU AGREE TO INDEMNIFY BiorefineryEPCTM , AND ITS AFFILIATES, OFFICERS, AGENTS, AND EMPLOYEES AGAINST ANY CLAIM OR DEMAND, INCLUDING REASONABLE ATTORNEYS' FEES, RELATED TO YOUR USE, RELIANCE, OR ADOPTION OF THE DATA FOR ANY PURPOSE WHATSOEVER. THE DATA ARE PROVIDED BY BiorefineryEPCTM "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY DISCLAIMED. IN NO EVENT SHALL BiorefineryEPCTM BE LIABLE FOR ANY SPECIAL, INDIRECT OR CONSEQUENTIAL DAMAGES OR ANY DAMAGES WHATSOEVER, INCLUDING BUT NOT LIMITED TO CLAIMS ASSOCIATED WITH THE LOSS OF DATA OR PROFITS, WHICH MAY RESULT FROM ANY ACTION IN CONTRACT, NEGLIGENCE OR OTHER TORTIOUS CLAIM THAT ARISES OUT OF OR IN CONNECTION WITH THE USE OR PERFORMANCE OF THE DATA.
This document provides an overview of freezing technology and the current status of frozen products in India. It discusses the history and development of freezing, defines key freezing terms, and describes the freezing process and factors that affect it. It also outlines different freezing methods like air freezing, contact freezing, and cryogenic freezing. The document concludes with advantages and disadvantages of freezing and statistics on India's frozen product industry which shows increasing production volumes and values from 2015-2018.
This document describes methods for determining the moisture content of crude drugs, including loss on drying and azeotropic distillation. Loss on drying is the common gravimetric method, which involves weighing a sample before and after drying in an oven at 100°C until the weight is constant. Azeotropic distillation is a volumetric method that uses toluene to distill any water in a sample into a graduated tube, allowing the volume of water to be measured and moisture content calculated based on the sample weight. Other instrumental methods like gas chromatography and NMR are also mentioned. The key steps of each technique are outlined.
Sublimation is a purification process where a solid transitions directly to its gas phase without passing through a liquid phase. It involves precise control of individual purification steps under vacuum or gas flow conditions. Sublimation is commonly used to purify pharmaceuticals and can also be used to create freeze-dried substances or porous drug tablets using a sublimating material like camphor. Another application is sublimating dye onto fabrics to create designs without affecting the fabric's feel or performance.
Lyotherm2: Thermal Analyses for Freeze Drying CharacterisationBTL
Lyotherm is a novel analytical instrument that combines DTA and Impedance Analysis to provide a thorough understanding of a product's freeze drying characteristics.
The document discusses a study that evaluated the impact of controlled nucleation on primary drying time during freeze drying. Two solutions of 5% sucrose were prepared, one with controlled nucleation at -3°C using ControLyo technology, and one without control that nucleated randomly down to -17°C. Primary drying times were determined using a Pirani/capacitance manometer differential. Controlled nucleation led to uniform nucleation of all vials at once and resulted in a primary drying time of 30.5 hours, compared to 40.4 hours for uncontrolled nucleation, a savings of 10 hours or 24%.
EXPERIMENT 8 PRECIPITATION HARDENING IN 2024 ALUMINUM .docxSANSKAR20
EXPERIMENT 8
PRECIPITATION HARDENING IN 2024 ALUMINUM
Objective
To study the time and temperature variations in the hardness of Al-4% Cu alloy on
isothermal aging.
Introduction
Materials can be hardened by inhibiting the motion of crystal defects called dislocations. In
pure metals, the presence of defects (such as vacancies, interstitials, dislocations and grain
boundaries) can enhance the strength. In single phase alloys, additional resistance to
deformation may arise from the presence of foreign atoms. In two-phase alloys, additional
stress is needed to enable the dislocation to intersect the second-phase particles. A finely
dispersed precipitate may, therefore, strengthen the material. This phenomenon is termed
precipitation hardening.
The thermodynamics of precipitation in 2024 Al can best be understood by referring to the
binary phase diagram of Aluminum-Copper in the aluminum-rich region in Figure 8-1.
When the aluminum-copper alloy of less than 5 wt% copper is heated to a temperature just
above the solvus line, only one phase (kappa, ) is thermodynamically stable. Other solid
phases dissolve (disappear). This process is called solution treatment. The only requirement
is that the specimen must be kept at this temperature for a long enough time. To solution
treat a sample of 2024 Al (4 wt% Cu), the sample should be heated to 930°F (500°C) and held
for 30 minutes.
When a solution treated sample is rapidly cooled (quenched) to below the solvus line (Figure
8-1), two phases are thermodynamically stable (kappa and theta). These phases are two
different solids, physically distinct, and separated by a phase boundary. The process is
similar to precipitation of salt in supersaturated brine.
The process of precipitation is not instantaneous, as is often the case in liquid-solid
precipitation. The process involves the formation of embryos of theta through thermal
fluctuations and their subsequent growth, once they achieve stability. With time, more and
more precipitates form. This process is called aging. Once the solution achieves an
equilibrium composition given by the solvus line for the aging temperature, precipitation
stops. For example, the precipitation of the copper-rich theta phase depletes the kappa phase
of copper to approximately 1-1/2 wt% Cu at 715°F (380°C).
The distribution of precipitates affects the hardness and yield strength. The hardness and
yield strength are greater when the precipitates are small and finely dispersed in the kappa
matrix than when the precipitates are large and not finely scattered. Therefore, to gain
hardness in 2024 Al, the specimen should be heat treated to produce a fine dispersion of
small precipitates.
Unfortunately, there is a tendency when thermodynamic equilibrium is reached for large
precipitates to grow and small precipitates to shrink. This will lower the surface to volume
ratio of the precip ...
Borosilicate glass has unique chemical and physical properties that make it well-suited for use in the chemical, food, pharmaceutical, and other industries. It has outstanding corrosion resistance, is transparent and inert. Borosilicate glass can withstand high temperatures up to 250°C and pressures depending on the component size. It also has low thermal expansion, is electrically insulating, and can be combined with other materials like PTFE. Borosilicate glass 3.3 is commonly used for its balance of properties.
This experiment studied the precipitation hardening behavior of an Al-4%Cu alloy by measuring changes in hardness over time during artificial and natural aging. Artificial aging at 190°C produced maximum hardness after 10 minutes that decreased after 1 week as precipitates coarsened. Natural aging reached maximum hardness more slowly over 1 week. Maintaining the alloy at 190°C could lead to precipitate coarsening and hardness loss over time.
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Investment materials developed in the first half of the twentieth century, to give clinically acceptable dental castings. But
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Silica exists in 22 different condensed phases. Five of these are amorphous, and 17 are crystalline; the latter are the polymorphs of silica.
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When this material is heated to the temperatures required for complete dehydration and sufficiently high to ensure complete castings, it shrinks
considerably and occasionally fractures.
The thermal expansion curves of the three common forms of gypsum products are shown in Figure. All forms shrink considerably after dehydration between 200" C and 400" C . A slight expansion takes place between 400" C and approximately 700, and a large contraction then occurs This shrinkage is most likely caused by decomposition and the release of sulfur gases, such as sulfur dioxide. This decomposition not only causes shrinkage but also contaminates the castings with the sulfides of the non-noble alloying elements, such as silver and copper.
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we are one of the leading manufacturers and exporters of a wide array of aluminum cooling towers, industrial aluminum cooling towers, copper heat exchangers, industrial copper heat exchangers, dry cooling towers, weather proof chillers, heat exchanger, cooling towers spares and wooden & RCC cooling tower. These are widely used in the oil refineries, distilleries and breweries plants, and fertilizer plant, cement plant, and engineering industry. Our Cooling Towers ranges from 10TR to 1000TR including FRP, Wooden, Dry, Fan less and Fill less Cooling Towers.
The document describes FIC's High Vapour Pressure (HVP) Forehearth, which represents an improvement in glass conditioning technology. The HVP Forehearth uses a unique design of thin, highly conductive "muffle tiles" that eliminate volatilization losses in glasses and provide more uniform heat transfer. This improves thermal homogeneity during glass conditioning and reduces defects compared to previous industry designs. Field testing shows benefits like decreased devitrification in borosilicate glass and improved response to job changes in opal glass.
Fouling, in technical language, it is the general term of unwanted material which is accumulating on surfaces, such as inside pipes, machines or heat exchanger.
This document provides information on the water treatment and electrical systems for the balance of plant for a 2x500MW thermal power project. It discusses the water requirements and sources, various water treatment processes, desalination processes, and electrical and control systems. The key points are: fresh water is a critical input for thermal power plants but availability is limited, so water conservation and reuse methods are discussed. Membrane and thermal desalination processes are described to supplement fresh water sources. Electrical systems including transformers, switchgear, cables, and control and instrumentation are outlined.
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BTL provides freeze-drying services including product characterization, formulation development, cycle development, and process optimization. Their team has extensive experience developing over 1000 products. They utilize two proprietary instruments, the Lyostat freeze-drying microscope and Lyotherm frozen state analyzer, to empirically determine critical product temperatures to inform development. BTL aims to establish a quantitative and science-led approach to streamline clients' freeze-drying processes.
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This presentation gives an overview into how advanced techniques such as manometric temperature measurement (MTM) and ice nucleation control can be used to enhance understanding of the freeze drying of your product, and provide additional control of its behaviour throughout the freeze drying cycle. This presentation was originally presented at Emerging Technologies in Freeze Drying, Stirling, 3rd April 2012.
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This document provides instructions for cryopreserving mouse embryos using a slow freeze/thaw method. It describes preparing the embryos and straws, loading the embryos into straws, seeding the straws to initiate crystallization, and freezing the straws at a controlled rate of 0.5°C per minute to reach -30°C, before plunging them into liquid nitrogen for storage. Attention to details like equipment, labeling, timing and data management are emphasized to ensure high survival rates for the cryopreserved embryos.
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The document summarizes an agenda for a conference on emerging technologies in freeze drying. The agenda includes presentations on using freeze drying microscopy to identify critical formulation parameters, using freeze drying in tissue engineering scaffold production, moisture mapping of a freeze dryer, and enabling process control in freeze drying through measurement of temperature, mass, and controlled nucleation technology. The document also provides information about freeze drying equipment manufacturers and service departments represented at the conference for food and pharmaceutical freeze drying applications.
1. A study of vial headspace moisture in
an entire freeze dried batch and the
factors affecting moisture content
variability
Isobel Cook
Principal Scientist
BTL– specialists in freeze drying research and development
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www.btl-solutions.net
2. Contents
• Freeze drying basics
• Moisture in the freeze dried product
• Frequency Modulated Spectroscopy (FMS)
• FMS and Karl Fischer moisture correlations
• Heat transfer within a freeze dryer
• Factors affecting moisture variation
• Frozen structure of mannitol
• Moisture mapping variations for 2% mannitol
• Further investigations
• FMS ratio variations over time
• Summary
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3. The freeze drying basics
Why? - Freeze drying can increase product shelf life from a few days to months/years.
Freeze drying involves removing the water from the material which involves three stages:
• Freezing - freeze the product to below its critical temperature
• Primary drying - remove the free ice by sublimation under vacuum
• Secondary drying - remove any remaining unfrozen water, the temperature
is typically raised above 0°C and the vacuum increased
For successful freeze drying:
• Choose suitable components
Freeze
for the formulation dried
• Establish the critical temperatures
for the product
Liquid fill Good cake Collapsed cake
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4. Moisture in the freeze dried product
The moisture content within a freeze dried material has a direct effect on the glass
transition (Tg) of the material. The Tg is the point at which a material can be observed
to undergo structural change, this has a direct effect on the
• Long term stability
• Storage temperature
Establishing moisture content uniformity is an important quality control tool
Moisture is commonly measured by Karl Fischer (KF) analysis and is often
considered the industry standard
• Measures the total water but
• Labour intensive
• Destroys the sample
• Uses toxic reagents
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5. Frequency Modulated Spectroscopy (FMS)
FMS enables the measurement of water and pressure within the headspace of the vial.
• The laser light is tuned to match the internal water absorption frequency at 1400nm
• The amount of laser light absorbed is proportional to the water vapour concentration
Analysis time ~ 5 seconds per vial
• Non-destructive (monitoring same vial over time)
• 100% inspection
Stopper
Sensor
Near infrared laser measures light
absorption
Vial headspace
Freeze dried material FMS-1400 (Lighthouse Instruments)
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6. FMS and Karl Fischer moisture correlations
Water may be present in a variety of “forms”/locations – free, adsorbed, chemically
bound, hydration shells (e.g. of proteins), water of crystallisation
Water can have different association/affinity within the freeze dried material which
varies with the formulation
Sucrose KF vs FMS Mannitol KF vs FMS
3.50 7.00
y = 1.0274x + 0.796 y = 0.4242x - 0.3634
3.00 R2 = 0.9894 6.00 R2 = 0.939
2.50 5.00
KF % water
2.00 4.00
% KF
1.50 3.00
1.00 2.00
0.50 1.00
0.00 0.00
0.00 0.50 1.00 1.50 2.00 2.50 0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00
FMS Torr FMS Torr
Intercept and gradient vary with the formulation based on intrinsic properties of
excipients and active
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7. Vial heat transfer in a freeze dryer
Heat transfer occurs by various means but is not uniform throughout the
batch.
Vapour escapes through
gap in stopper
Heat transfer by
radiation from side
walls of the freeze Top layer dries first
dryer
Heat transfer by Central vials have greater
direct conduction shielding from side wall
from the shelf to radiation
the vial and
product
Heat transfer by gaseous
Freeze dryer shelf convection
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8. Factors affecting moisture variation
Moisture content of samples in a tray
Heat transfer by
• Conduction
• Gaseous convection
Degree of shelf contact
• Tray
• Direct shelf contact
• Sample container Moisture content of samples with direct shelf contact
Radiative heating from freeze dryer
• Freeze dryer door
• Freeze dryer walls
• Extent of shielding
Cycle/processing conditions responsible for observed differences
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9. Frozen structure of Mannitol
Annealing involves cooling and re-warming of the frozen structure
• Encourages crystallisation
• Encourages the growth of larger ice crystals (slower cooling larger ice crystals)
It is easier for vapour to
Annealing escape
Energy input required
More ordered
reduced
open structure
Structure reduces the impact of heat transfer variation due to shelf contact
Gaseous convection not observed as open structure allows for efficient drying
Material structure and treatment can have large impact on the observed moisture
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10. Moisture mapping variations for 2% Mannitol
• Freeze drying cycle involved an annealing step to encourage crystallisation
• Primary drying conducted at -5°C, Vacuum set at 1000 mtorr
Mannitol-Headspace Moisture (Direct) Mannitol-Headspace Moisture (Tray)
20 20
18 18
16 16
14 14
Moisture (Torr)
Moisture (Torr)
12 12
10 10
8 8
6 6
4 4
2 2
0 0
1
11
21
31
41
51
61
71
81
91
101
111
121
131
141
151
161
171
181
191
201
211
221
231
1
12
23
34
45
56
67
78
89
100
111
122
133
144
155
166
177
188
199
210
221
232
243
Vial number Vial number
• Direct shelf contact • No direct shelf contact (Tray)
• Average torr 5.24 / ~ 2 % KF • Average torr 4.72 / ~ 2 % KF
• Standard deviation 2.31 • Std deviation 1.30
Sample sets have a similar moisture content – gaseous convection plays a role!
Significant variation within each sample set
Tray samples have a lower standard deviation – Related to slower cooling rate
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11. Moisture mapping variations for 2% Mannitol
• Freeze drying cycle involved an annealing step to encourage crystallisation
• Primary drying at -40°C, Vacuum set at 50 mtorr, shortened secondary drying
Mannitol-Headspace Moisture (Direct) Mannitol-Headspace Moisture (Tray)
20 20
18 18
16 16
14 14
Moisture (Torr)
Moisture (Torr)
12 12
10 10
8 8
6 6
4 4
2 2
0 0
1
12
23
34
45
56
67
78
89
100
111
122
133
144
155
166
177
188
199
210
221
232
243
1
12
23
34
45
56
67
78
89
100
111
122
133
144
155
166
177
188
199
210
221
232
243
Vial number Vial number
• Direct shelf contact • No direct shelf contact (Tray)
• Average torr 10.31 • Average torr 9.69
• Standard deviation 2.79 • Standard deviation 2.12
Sample sets have a similar moisture content – gaseous convection not a factor!
Higher moisture results for both sets due to shortened secondary drying step
Significant variation within each tray
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12. Further investigations
Freeze dried mannitol can exist in several forms:
• Amorphous mannitol
• Crystalline hydrate(s) of mannitol
• Anhydrous crystalline mannitol - Alpha (α), beta (β) and delta (δ)
Mannitol KF vs FMS
7.00
y = 0.3191x - 0.0673
Further analysis and closer 6.00 R2 = 0.6003
inspection of the KF/FMS 5.00
KF % water
4.00
correlation revealed a
3.00
deviation and lack of 2.00
correlation for some samples 1.00
0.00
0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00
FMS (torr)
This variation appeared to be related to a change in the mannitol form (observed
by comparing FMS data over several days)
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13. FMS ratio variations over time
Direct shelf contact batch
• Higher ratio change
• Random spread
(highest ratio change
towards front half of
tray) Ratio change= Day 3 / Day 1 Green = no / small change
Mannitol-Headspace Moisture (Direct)
20
High level of variation observed for 18
16
headspace moisture Moisture (Torr)
14
12
Standard deviation 2.31 10
8
6
4
Indicate headspace moisture variation 2
within a shelf related to the different 0
1
11
21
31
41
51
61
71
81
91
101
111
121
131
141
151
161
171
181
191
201
211
221
231
proportion of mannitol crystalline forms Vial number
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14. FMS ratio variations over time
No direct contact (tray)
batch
• Lower ratio change
• Random spread
(Higher ratio changes
towards tray edge) Ratio change= Day 3 / Day 1 Green = no / small change
Mannitol-Headspace Moisture (Tray)
20
18
Lower level of variation observed for 16
headspace moisture 14
Moisture (Torr)
12
Standard deviation 1.30 10
8
6
4
2
Indicate slower heat transfer results in 0
1
12
23
34
45
56
67
78
89
100
111
122
133
144
155
166
177
188
199
210
221
232
243
more controlled crystallisation and a Vial number
smaller variation in mannitol form
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15. Summary
Headspace moisture analysis can be used as a non-destructive method to further our
understanding of the factors involved in obtaining a uniform moisture content
Processing factors
• Efficiency of heat transfer – conduction and convection, container material
• Degree of shelf contact e.g. tray/no tray, container shape
• Radiative heating – larger shelves = fewer vials exposed to side wall radiation
• Annealed or non-annealed - ice crystal size, pathways for vapour to escape
• Cooling and re-warming rates
Excipients/active material
• Material type/structure e.g. amorphous or crystalline, material complexity
It is important to fully understand reasons for moisture variation due to
processing and material choices.
This understanding can assist in validation and in assessing any changes
made.
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16. For more on FMS, vial headspace
analysis, or freeze drying product and
process analysis, visit
www.btl-solutions.net
Isobel Cook
Principal Scientist
BTL- specialists in freeze drying research and development
www.btl-
www.btl-solutions.net