If you have been reading about Primary drying and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2026-06-18. Numbers and descriptions here follow the published literature rather than marketing material.
Lyophilization, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
The process relies on the phase diagram of water, where the triple point marks the conditions at which ice, liquid water, and vapor coexist. By maintaining pressure below this point, typically around 0.01 to 0.1 millibar, sublimation becomes the dominant mechanism. Formulations often include excipients such as sugars or polymers that act as lyoprotectants and bulking agents. These additives help preserve the structure of the active ingredient and prevent collapse during drying. The choice of excipient and freezing rate influences the final cake morphology and stability.
Industries use lyophilization for pharmaceuticals, biological products, and food preservation. In the pharmaceutical sector, it extends the shelf life of injectable drugs, vaccines, and proteins that are unstable in aqueous solution. Food manufacturers apply freeze-drying to coffee, fruits, and ready meals to retain flavor and texture. The process is energy-intensive and requires specialized equipment, which limits its use to high-value products. Ongoing research examines how formulation and process parameters affect the quality of the final dried product.
A typical cycle begins with freezing, which fixes the material into a solid and determines ice crystal size. Primary drying then raises heat under vacuum so ice sublimes, often near or below the collapse temperature of the formulation. Secondary drying removes bound water that remains after ice is gone, usually by gently warming the product. Each stage balances heat input against pressure to avoid melting or structural damage. Temperature probes and pressure sensors guide the transition between stages.
In practice, lyophilization is slower and more energy intensive than simple drying. Cycle times can range from hours to several days depending on load, container, and formulation. Amorphous materials may require excipients that help preserve structure during freezing and drying. The method is widely used for biological materials, pharmaceuticals, and foods where heat drying would cause unacceptable change. Open questions remain about scaling cycles between laboratory and production equipment, and this gap affects technology transfer.
Lyophilization removes water by freezing a material and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intermediate liquid state. Because the material remains frozen during primary drying, the structure often stays porous. This porous matrix can rehydrate quickly when water is added back. The low pressure also allows vapor to leave the solid matrix without boiling.
| Property | Value | Notes |
|---|---|---|
| Common name | Freeze-drying | Lyophilization is the technical synonym. |
| Typical chamber pressure | 0.01–0.1 mbar | Below the triple point of water. |
| Primary drying temperature | −40 to −10 °C | Depends on formulation and equipment. |
| Residual moisture | 1–5% | Target for many pharmaceutical products. |
| Typical equipment | Vacuum freeze-dryer | Includes drying chamber and condenser. |
Freeze-drying is distinct from simple evaporation and from spray drying. Evaporation removes water at temperatures above freezing, while spray drying rapidly dries droplets in a heated gas stream. Lyophilization avoids high temperatures, which can be useful for heat-sensitive materials such as proteins, vaccines, and some foods. The porous cake produced by sublimation dissolves or rehydrates more quickly than a dense dried mass. Not all materials tolerate freezing or the pH shifts that can occur as solutes concentrate during ice formation.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and fixes the structure of the sample. After freezing, primary drying lowers pressure so ice changes directly to vapor without passing through a liquid phase. Secondary drying then removes bound water that remains after ice sublimation. The result is a dry, porous solid that often retains its original shape.
The low pressure used during drying allows water vapor to move from the ice surface to a cold condenser. Energy supplied as heat drives sublimation but must stay below the collapse temperature of the frozen matrix. If the product becomes too warm, the frozen structure may soften or melt, reducing pore formation and slowing drying. Formulations often include bulking agents, stabilizers, or buffers to support a rigid cake. The final moisture content depends on formulation, freezing rate, and the length of secondary drying.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback during drying.
A formulation often contains excipients that protect the active ingredient during freezing and drying. Bulking agents provide structure, while lyoprotectants stabilize sensitive molecules. The freezing step can produce ice crystals whose size and distribution affect the drying rate, and cycle design includes freezing, annealing, and drying phases. If the product temperature rises above a critical value, the cake may collapse or lose its porous structure. Successful lyophilization therefore depends on the interaction between formulation, equipment, and cycle design.
Comparative genomics approaches were used to predict the function-relevant variants under the assumption that the functional genetic locus should be conserved across different species at an extensive phylogenetic distance. On the other hand, some adaptive traits and the population differences are driven by positive selections of advantageous variants, and these genetic mutations are functionally relevant to population specific phenotypes. Functional prediction of variants' effect in different biological processes is pivotal to pinpoint the molecular mechanism of diseases/traits and direct the experimental validation.
Approximately 0.2 to 1% of people have a "weak D" phenotype, meaning that they are positive for the RhD antigen, but exhibit weak or negative reactions with some anti-RhD reagents due to decreased antigen expression or atypical variants of antigen structure. If routine serologic testing for RhD results in a score of 2+ or less, the antiglobulin test can be used to demonstrate the presence of RhD. Weak D testing is also performed on blood donors who initially type as RhD negative. Historically, blood donors with weak D were treated as Rh positive and patients with weak D were treated as Rh negative in order to avoid potential exposure to incompatible blood. Genotyping is increasingly used to determine the molecular basis of weak D phenotypes, as this determines whether or not individuals with weak D can produce antibodies against RhD or sensitize others to the RhD antigen.
The enthalpy of sublimation, measured through testing of fermium alloys, is calculated at 33.8±3 kcal/mol (141.4±12.6 kJ/mol) derived from Second Law values, and 34.8 kcal/mol (145.6 kJ/mol) derived from Third Law values, both at 298 K. Through this, fermium is considered a divalent metal.
As a result, the more interesting possibilities remain on the table and the mystery of the tension deepens." Research suggests that replacing half of the beef, chicken, dairy and pork products consumed globally with plant-based alternatives by 2050 could reduce the amount of land used by agriculture by almost a third, bring deforestation for agriculture nearly to a halt, help restore biodiversity through rewilding the land and reduce GHG emissions from agriculture by 31%, paving a clearer path to reaching climate and biodiversity targets. A separate study (6 Sep) using a global food system model suggests that net-negative greenhouse gas emissions could be possible in a sustainable food system achievable with full global deployment of diverse interventions, with the most promising options including hydrogen-powered fertilizer production, livestock feeds, organic and inorganic soil amendments, agroforestry, sustainable seafood harvesting practices, and adoption of flexitarian diets. 18 September A new palm oil substitute called PALM-ALT is presented by researchers. The plant-based ingredient is shown to be 70% better for the environment than conventional palm oil and is described as "the holy grail to replace it". The Linac Coherent Light Source at the SLAC National Accelerator Laboratory is upgraded to LCLS-II and successfully demonstrates its first X-rays, which are fired 8,000 times faster and are 10,000 times brighter than the previous version.
Sources: en.wikipedia.org
== Growth and morphology == The filamentous non-soil associated fungus does not require any specific growth condition in culture. E. floccosum does not grow on urease culture, has low osmotolerance, and is unable to form perforating organs. The colonies have khaki suede-like flat surfaces and grow moderately rapidly, reaching maturity within 10 days. The reverse is reddish-brown. Colonies are initially flat, but the centre of which later becomes raised and folded, with the periphery submerged. On rich media like Sabouraud agar, colonies usually degenerate into white pleomorphic tufts within several weeks, and sometimes exude a red-brown pigment into its agar. E. floccosum has septate, hyaline hyphae. Its key features are the smooth, thin-walled, club-shaped macroconidia and the absence of microconidia. The macroconidia are borne singly or in clusters of 2 or 3; they are 20–40 μm in length and 7–12 μm in width, consisting of 1 to 9 septa. The narrow base and broad, club-shaped apex of the macroconidium have been compared in shape to a beaver tail. The fungus reproduces asexually through chlamydoconidia, which are resting spores that are abundant in culture. Arthroconidia are also abundant in the culture, emerging as swollen cells alongside macroconidia formation; these thick-walled spores are resistant to heat and drying conditions.
Extended-release (or slow-release) formulations of morphine are those whose effect lasts substantially longer than bare morphine, availing for, e.g., one administration per day. Conversion between extended-release and immediate-release (or "regular") morphine is easier than conversion to or from an equianalgesic dose of another opioid with different half-life, with less risk of altered pharmacodynamics.
=== Removal rate === A drug's removal rate will be determined by the proportion of the drug that is removed from circulation by each organ once the drug has been delivered to the organ by the circulating blood supply. This new concept builds on earlier ideas and it depends on a number of distinct factors:
== Diagnosis == The initial clinical evaluation of a suspected TIA involves obtaining a history and physical exam (including a neurological exam). History taking includes defining the symptoms and looking for mimicking symptoms as described above. Bystanders can be very helpful in describing the symptoms and giving details about when they started and how long they lasted. The time course (onset, duration, and resolution), precipitating events, and risk factors are particularly important. The definition, and therefore the diagnosis, has changed over time. TIA was classically based on duration of neurological symptoms. The current widely accepted definition is called "tissue-based" because it is based on imaging, not time. The American Heart Association and the American Stroke Association (AHA/ASA) now define TIA as a brief episode of neurological dysfunction with a vascular cause, with clinical symptoms typically lasting less than one hour, and without evidence of significant infarction on imaging.
At pH > 8, silica itself may dissolve. When solutions at extreme pH are needed, the stationary phase can be made of silica polymerized with organic substances, or hydrophobic organic polymers. With such stationary phases, retention time is longer for nonpolar molecules, whereas polar molecules elute more readily (emerge early in the analysis). A chromatographer can increase retention times by adding more water to the mobile phase. Since water is highly polar, it makes the nonpolar analyte interact more strongly with nonpolar stationary phase. Similarly, an investigator can decrease retention time by adding more organic nonpolar solvent to the mobile phase. RP-HPLC operates on the principle of hydrophobic interactions, which originates from the high symmetry in the dipolar water structure and plays the most important role in all processes in life science. RP-HPLC allows the measurement of these interactive forces. The binding of the analyte to the stationary phase is proportional to the contact surface area around the non-polar segment of the analyte molecule upon association with the ligand on the stationary phase. This solvophobic effect is dominated by the force of water for "cavity-reduction" around the analyte and the C18-chain versus the complex of both. The energy released in this process is proportional to the surface tension of the eluent (water: 7.3×10−6 J/cm2, methanol: 2.2×10−6 J/cm2) and to the hydrophobic surface of the analyte and the ligand respectively.
Sources: en.wikipedia.org
=== Education === Yonath was accepted to Tichon Hadash high school since her mother could not pay the tuition, she traded her time teaching math lessons to students, which helped pay for her schooling. At a young age, she said, she was inspired by the scientist Marie Curie. However, she stressed that Curie, whom she as a child was fascinated by after reading her biography, was not her "role model". She returned to Jerusalem for college, graduating from the Hebrew University of Jerusalem with a bachelor's degree in chemistry in 1962, and a master's degree in biochemistry in 1964. In 1968, she obtained her PhD from the Weizmann Institute of Science for X-ray crystallographic studies on the structure of collagen, with Wolfie Traub as her PhD advisor.
Each size exclusion column has a range of molecular weights that can be separated. The exclusion limit defines the molecular weight at the upper end of the column 'working' range and is where molecules are too large to get trapped in the stationary phase. The lower end of the range is defined by the permeation limit, which defines the molecular weight of a molecule that is small enough to penetrate all pores of the stationary phase. All molecules below this molecular mass are so small that they elute as a single band. The filtered solution that is collected at the end is known as the eluate. The void volume includes any particles too large to enter the medium, and the solvent volume is known as the column volume. Following are the materials which are commonly used for porous gel beads in size exclusion chromatography
=== DNA barcoding and genomics === DNA sequences derived from fungarium specimens can link preserved material to molecular characters used in identification and phylogenetic studies, extending the scientific value of collections beyond traditional morphological characters. Sequencing named fungarium specimens can also expand public reference-sequence databases, improving the interpretation of environmental fungal DNA that would otherwise remain unidentified or only insufficiently identified. DNA in historical specimens is often degraded into short fragments of 40–400 base pairs. Genetic quality is influenced by the specimen's age as well as past exposure to heat, chemicals, or moisture. Consequently, older specimens are less likely to yield uncontaminated internal transcribed spacer (ITS) sequences than more recent collections, often producing DNA from contaminant organisms instead. DNA degradation depends not only on age but also on how specimens were collected, dried, stored, and treated against pests, because historical methods often prioritized preservation of morphology rather than nucleic-acid integrity. Conventional PCR amplification and Sanger sequencing can be difficult or impossible for some specimens, including some type material, owing to fragmentation and contamination by exogenous fungal DNA.
Iron, zinc, calcium, copper, magnesium, selenium and molybdenum are among the essential minerals having stable isotopes to which isotope tracer methods have been applied. Iron, zinc and calcium in particular have been extensively studied. Aspects of mineral nutrition/metabolism that are studied include absorption (from the gastrointestinal tract into the body), distribution, storage, excretion and the kinetics of these processes. Isotope tracers are administered to subjects orally (with or without food, or with a mineral supplement) and/or intravenously. Isotope enrichment is then measured in blood plasma, erythrocytes, urine and/or feces. Enrichment has also been measured in breast milk and intestinal contents. Tracer experiment design sometimes differs between minerals due to differences in their metabolism. For example, iron absorption is usually determined from incorporation of tracer in erythrocytes whereas zinc or calcium absorption is measured from tracer appearance in plasma, urine or feces. The administration of multiple isotope tracers in a single study is common, permitting the use of more reliable measurement methods and simultaneous investigations of multiple aspects of metabolism. The measurement of mineral absorption from the diet, often conceived of as bioavailability, is the most common application of isotope tracer methods to nutrition research. Among the purposes of such studies are the investigations of how absorption is influenced by type of food (e.g., plant vs. animal source, breast milk vs. formula), other components of the diet (e.g.
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate water from a material, while lyophilization freezes the material and removes water by sublimation under vacuum. This avoids the liquid phase and reduces thermal damage to sensitive substances. The result is a porous cake that reconstitutes quickly.
A vacuum lowers the pressure below the triple point of water, allowing ice to sublimate directly into vapor without melting. It also removes water vapor from the product chamber and speeds up the drying process. Without vacuum, the ice would melt rather than sublimate.
Not all substances are suitable for lyophilization. Materials must form a stable frozen matrix and tolerate freezing and low pressure. Some small molecules, oils, or volatile compounds may not form a proper cake or may be lost during processing.
Primary drying removes ice by sublimation under vacuum. Secondary drying removes water that is bound to the material, often by warming the product after most ice has left. Both stages occur below temperatures that would cause unwanted melting.