A practical reference on Sublimation: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2026-05-09 and is reviewed periodically as new material appears.
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
Secondary drying removes bound water that remains after ice sublimation. Shelf temperature is raised gradually while pressure remains low, reducing water content to a target range. Over-drying can cause brittleness or electrostatic issues, while under-drying affects stability. The endpoint is often judged by pressure rise tests, temperature measurements, or water content analysis. Scale-up depends on matching heat and mass transfer across equipment sizes. Small changes in shelf temperature or pressure can alter cycle length substantially.
Lyophilization, or freeze-drying, removes water from a material by freezing it and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intervening liquid state. It is used for heat-sensitive materials that would degrade in conventional drying. The three stages are freezing, primary drying, and secondary drying, each with distinct temperature and pressure requirements. In practice, cycle design balances these variables.
Reconstitution involves adding a suitable diluent, often sterile water or a buffer, to the dried cake. Gentle swirling or inversion helps dissolve the material without creating excessive foam. The time required for complete dissolution can range from seconds to several minutes and depends on the cake structure and the diluent. Improper reconstitution, such as vigorous shaking or using the wrong diluent, can cause protein aggregation or loss of activity. After reconstitution, the product may have a limited shelf life and should be used according to its labeling.
Lyophilized products are typically hygroscopic and require protection from moisture during storage. Manufacturers seal them in glass vials, often under vacuum or an inert gas such as nitrogen. The container closure system, including the stopper and crimp seal, must prevent water vapor ingress. Storage temperature varies from controlled room temperature to refrigerated or frozen conditions, depending on the formulation. Humidity-controlled environments are essential because even brief exposure to ambient air can degrade the product.
Stability of a lyophilized product depends on its glass transition temperature, the temperature at which the amorphous cake transitions from a glassy to a rubbery state. Storage below this temperature minimizes molecular mobility and slows chemical degradation. If the storage temperature exceeds the glass transition temperature, the cake may collapse, shrink, or become sticky. Accelerated stability studies at elevated temperatures and humidity help predict shelf life, but they do not always reflect real-time behavior. Residual moisture content also plays a critical role in long-term stability.
| Property | Value | Notes |
|---|---|---|
| Process name | Lyophilization or freeze-drying | Both terms appear in technical standards and literature. |
| Phase transition | Sublimation | Solid ice becomes vapor without a liquid step. |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product temperature and equipment. |
| Typical product temperature | -40 °C to -10 °C | Measured during primary drying; formulation sets limits. |
| Water content after drying | 0.5-3% w/w | Target varies by material and stability needs. |
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.
Regulatory expectations for lyophilized products focus on consistent manufacture and documented stability. Batches are often monitored for moisture, appearance, potency, and sterility where applicable. Process parameters such as shelf temperature, chamber pressure, and drying time are recorded and controlled within validated ranges. Open questions remain about how best to predict long-term stability from short accelerated studies, especially for complex biologics. Variations in freezing rate and ice crystal size can produce differences that are not always visible but may affect performance.
After drying, a lyophilized product is usually sealed under vacuum or an inert gas to limit moisture uptake. Residual water content is measured because small changes can alter chemical stability and cake appearance. Storage temperature depends on the material; many biological products are kept at 2–8 °C, while some require −20 °C or colder. Exposure to ambient humidity during handling can cause the porous solid to absorb water and collapse. Container closures and stoppers are therefore selected for low moisture transmission and compatibility.
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.
=== Inappropriate secretion, associated with hypoglycemia === Hyperinsulinism may also refer to forms of hypoglycemia caused by excessive insulin secretion. In normal children and adults, insulin secretion should be minimal when blood glucose levels fall below 70 mg/dL (3.9 mM). There are many forms of hyperinsulinemic hypoglycemia caused by various types of insulin excess. Some of those that occur in infants and young children are termed congenital hyperinsulinism. In adults, severe hyperinsulinemic hypoglycemia is often due to an insulinoma, an insulin-secreting tumor of the pancreas. Insulin levels above 3 μU/mL are inappropriate when the glucose level is below 50 mg/dL (2.8 mM), and may indicate hyperinsulinism as the cause of the hypoglycemia. The treatment of this form of hyperinsulinism depends on the cause and the severity of the hyperinsulinism, and may include surgical removal of the source of insulin, or a drug such as diazoxide or octreotide that reduces insulin secretion. That spontaneous hyperinsulinism might be a cause of symptomatic hypoglycemia was first proposed by Seale Harris, MD, 1924, in Journal of the American Medical Association. Dr. Seale Harris first diagnosed hyperinsulinism in 1924 and also is credited with the recognition of spontaneous hypoglycemia.
Hydrometallurgy is a technique within the field of extractive metallurgy, the obtaining of metals from their ores. Hydrometallurgy uses solutions to recover metals from ores, concentrates, and recycled or residual materials. Usually the extracting solution is aqueous (water-based), often containing additives such as acids. In select cases, the extracting solvent is nonaqueous. Processing techniques that complement hydrometallurgy are pyrometallurgy, vapour metallurgy, and molten salt electrometallurgy. Hydrometallurgy is typically divided into three general areas:
=== Expansion === The company opened locations in Arizona in 2000 and added new restaurants in Reno, Sparks, and Carson City, Nevada, in late 2004. In-N-Out became a huge success in these new locations. In late December 2005, In-N-Out's 200th location was opened in Temecula, California. In 2007, it opened its first restaurant in Tucson, Arizona. The store opening broke company records for the most burgers sold in one day and the most sold in one week. In 2008, In-N-Out expanded into a fourth state by opening a location in Washington, Utah, a suburb of St. George. By late 2009, the chain expanded into northern Utah with three new locations situated in Draper, American Fork, and Orem. More locations opened in the spring of 2010 in West Valley City, West Jordan, Centerville, and Riverton. In 2013, In-N-Out opened a distribution center in Las Vegas to serve mountain area restaurants.
Genetic screens conducted in Drosophila led to the identification of several proteins that play a central role in Notch signaling, including Enhancer of split, Master mind, Delta, Suppressor of Hairless (CSL), and Serrate. At the same time, the Notch gene was successfully sequenced and cloned, providing insights into the molecular architecture of Notch proteins and led to identification of Notch homologs in Caenorhabditis elegans (C. elegans) and eventually in mammals. In the early 1990s Notch was increasingly implicated as the receptor of a previously unknown intercellular signal pathway in which the Notch intercellular domain (NICD) is transported to the nucleus where it acts as a transcription factor to directly regulate target genes. The release of the NICD was found to be as a result of proteolytic cleavage of the transmembrane protein through the actions of the γ-secretase complex catalytic subunit Presenilin. This was a significant interaction as Presenilin is implicated in the development of Alzheimer's disease. This and further research into the mechanism of Notch signaling led to research that would further connect Notch to a wide range of human diseases.
ideal gas law Also general gas equation. The equation of state of a hypothetical ideal gas, which states that the volume of such a gas is proportional to the amount of gas and its Kelvin temperature, and inversely proportional to its pressure. The ideal gas law combines Boyle's law, Charles's law, Gay-Lussac's law, and Avogadro's law into a single equation, conventionally formulated as
Sources: en.wikipedia.org
1 April – Artemis program: NASA launches the Artemis II lunar flyby mission from Launch Complex 39B at the Kennedy Space Center in Florida, the first crewed flight beyond low Earth orbit since Apollo 17 in 1972. With a crew of four astronauts – Reid Wiseman (Commander) Victor Glover (Pilot), Christina Koch (Mission specialist), and Canadian astronaut Jeremy Hansen (Mission specialist) – it also becomes the first time a person of color, a woman, and a non-United States citizen have left low Earth orbit. It passed around the Moon's far side on April 6. 2 April Scientists describe a transitional fauna of the late Ediacaran from Yunnan in China, which fills a gap between ancestors of modern phyla and larger multicellular life. Astronomers using preliminary data from the Vera C. Rubin Observatory announce the discovery of over 11,000 new asteroids, including hundreds of trans-Neptunian objects and 33 previously unknown near-Earth objects. The detections are confirmed by the Minor Planet Center. 6 April – In a landmark achievement for India's nuclear energy programme, the 500 MWe Prototype Fast Breeder Reactor successfully attains first criticality (start of controlled fission chain reaction). 6 April – The crew of Artemis II breaks the record for the furthest humans have ever been from Earth, reaching a maximum distance of 252,757 miles (406,773 km) as they travel around the far side of the Moon.
==== Yeast Two-hybrid Screens ==== Yeast two-hybrid analyses have been adapted for protease-substrate discovery. As protease exosites play roles in protein-protein recognition and interaction, biologists have used exosites as tools to screen for protease interactors and potential substrates. These protease exosite scanning assays use protease exosites as bait to scan a cDNA library for possible interacting partners. Another early adaptation of yeast two-hybrid screening in protease-substrate discovery is Inactive-catalytic-domain capture (ICDC). This approach attempts to avoid the limitation of protease exosite scanning, which fails to account for any substrates that do not require exosites to for recognition before cleavage. The bait for these assays are immobilized catalytically inactive mutant protease domains that cannot cleave and release their substrates once bound. While useful in early degradomic studies, the limitations of adapted yeast two-hybrid screens have forced the field to move on to higher-throughput approaches for protease-substrate discovery. Their high rate of false positives and negatives, inability to recognize complex interactions, lack of biologically compartmentalization, and failure to account for post-translational modifications necessary for protein-protein interactions hamper their usefulness. Thus they have been largely replaced by proteomic methods as technology has improved.
=== COVID-19 === At the start of the COVID-19 pandemic, some doctors observed that anecdotally some hospitalized patients in China may have had better outcomes on famotidine than other patients who were not taking famotidine. This led to hypotheses about use of famotidine in treatment of COVID-19. Famotidine was considered a possible treatment for COVID-19 due to its potential anti-inflammatory effects. It was thought that famotidine could modify lung inflammation caused by coronaviruses. However, studies have shown that famotidine is not effective in reducing mortality or improving recovery in COVID-19 patients. Famotidine primarily works by blocking the effects of histamine and has some potential mechanisms of action that may contribute to its anti-inflammatory properties, including the inhibition of the production of certain pro-inflammatory cytokines such as TNF-alpha and IL-6. Another hypothesis was that famotidine might activate the vagus nerve inflammatory reflex to attenuate cytokine storm. Yet another hypothesis was that famotidine can reduce the activation of mast cells and the subsequent release of inflammatory mediators, therefore acting as a mast cell stabilizer. However, while famotidine may have some anti-inflammatory effects, there is currently insufficient evidence to support its use for treating inflammation associated with COVID-19. Therefore, it is not recommended for this purpose.
=== 2009: Norovirus outbreak === On 27 February 2009, Blumenthal closed the Fat Duck temporarily after a number of customers reported feeling unwell at different times. On 6 March, it was reported that 400 people had stated they had felt unwell after eating at the restaurant. The cause was later given by the Health Protection Agency as norovirus, thought to have originated from oysters harvested from beds contaminated with sewage. The virus spread further after being contracted by staff members. The Fat Duck was criticised for its cleaning methods and its slow response, and received 529 complaints of illness. It was the largest norovirus outbreak ever documented at a restaurant. The Fat Duck reopened on 12 March 2009.
Sources: en.wikipedia.org
Finally, a rather rare and exotic side reaction is known as cine substitution. Here, after initial oxidative addition of an aryl halide, this Pd-Ar species can insert across a vinyl tin double bond. After β-hydride elimination, migratory insertion, and protodestannylation, a 1,2-disubstituted olefin can be synthesized.
Aminoacyl-tRNA synthetase enzymes consume ATP in the attachment tRNA to amino acids, forming aminoacyl-tRNA complexes. Aminoacyl transferase binds AMP-amino acid to tRNA. The coupling reaction proceeds in two steps: aa + ATP ⟶ aa-AMP + PPi aa-AMP + tRNA ⟶ aa-tRNA + AMP The amino acid is coupled to the penultimate nucleotide at the 3′-end of the tRNA (the A in the sequence CCA) via an ester bond (roll over in illustration). Transporting chemicals out of a cell against a gradient is often associated with ATP hydrolysis. Transport is mediated by ATP binding cassette transporters. The human genome encodes 48 ABC transporters, that are used for exporting drugs, lipids, and other compounds.
Collisional excitation in mass spectrometry is the process where an ion collides with an atom or molecule and leads to an increase in the internal energy of the ion. Molecular ions are accelerated to high kinetic energy and then collide with neutral gas molecules (e.g. helium, nitrogen or argon). In the collision some of the kinetic energy is converted into internal energy which results in fragmentation in a process known as collision-induced dissociation. Collision-induced absorption and emission
As part of the Synthetic Yeast 2.0 project, various research groups around the world have participated in a project to synthesise synthetic yeast genomes, and through this process, optimise the genome of the model organism Saccharomyces cerevisiae. The Yeast 2.0 project applied various DNA assembly methods that have been discussed above, and in March 2014, Jef Boeke of the Langone Medical Centre at New York University, revealed that his team had synthesized chromosome III of S. cerevisiae. The procedure involved replacing the genes in the original chromosome with synthetic versions and the finished synthetic chromosome was then integrated into a yeast cell. It required designing and creating 273,871 base pairs of DNA – fewer than the 316,667 pairs in the original chromosome. In March 2017, the synthesis of 6 of the 16 chromosomes had been completed, with synthesis of the others still ongoing.
== Preparation and purification == The isotopes of nobelium are mostly produced by bombarding actinide targets (uranium, plutonium, curium, californium, or einsteinium), with the exception of nobelium-262, which is produced as the daughter of lawrencium-262. The most commonly used isotope, 255No, can be produced from bombarding curium-248 or californium-249 with carbon-12: the latter method is more common. Irradiating a 350 μg cm−2 target of californium-249 with three trillion 73 MeV carbon-12 ions per second for ten minutes can produce around 1200 nobelium-255 atoms. Once the nobelium-255 is produced, it can be separated out similarly as used to purify the neighboring actinide mendelevium. The recoil momentum of the produced nobelium-255 atoms is used to bring them physically far away from the target from which they are produced, bringing them onto a thin foil of metal (usually beryllium, aluminium, platinum, or gold) just behind the target in a vacuum: this is usually combined by trapping the nobelium atoms in a gas atmosphere (frequently helium), and carrying them along with a gas jet from a small opening in the reaction chamber. Using a long capillary tube, and including potassium chloride aerosols in the helium gas, the nobelium atoms can be transported over tens of meters. The thin layer of nobelium collected on the foil can then be removed with dilute acid without completely dissolving the foil.
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.
Lowering pressure reduces the boiling point of water and allows ice to sublimate at temperatures below freezing. Vacuum also limits convective heat transfer, so heat is usually supplied by shelves or radiation. The pressure must stay below the vapor pressure of ice at the product temperature.
The cycle typically includes freezing, primary drying, and secondary drying. Freezing solidifies water and sets the pore structure; primary drying removes bulk ice; secondary drying removes bound water. Some cycles add annealing or pre-freezing steps.
Lyophilized products should be stored in airtight containers, protected from moisture and light, at the temperature specified by the manufacturer. Many require refrigeration at 2–8 °C, while some need frozen storage. Always check the product label for specific conditions.