Sublimation comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2025-10-27. Where a claim depends on a specific study, the study is described rather than over-claimed.
Lyophilization is a dehydration technique in which a product is frozen and the solvent is removed under reduced pressure. The low pressure allows ice to sublimate directly into vapor without passing through a bulk liquid phase. This differs from conventional drying, where heat drives evaporation and can damage heat-sensitive structures. The process is used for biological materials, pharmaceutical formulations, and some foods. Its main advantage is preservation of porous structure and rapid reconstitution.
Freezing is the first stage and sets the ice structure that later becomes the pore network. The formulation is cooled below its freezing point, often with a controlled ramp, and solutes concentrate as ice forms. Primary drying then lowers chamber pressure and supplies heat to sublime the ice. The product temperature must stay below its collapse or eutectic temperature to prevent structural loss. Secondary drying raises the temperature modestly to remove bound water and achieve a low residual moisture.
A freeze-dryer consists of a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. Vials, ampoules, or bulk trays hold the product during the cycle. The condenser traps water vapor as ice at a temperature lower than the product. Cycle development balances shelf temperature, chamber pressure, and time. Scale-up can be difficult because heat and mass transfer change with equipment size, so process analytical tools and conservative validation are often used.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | freeze-drying, lyophilisation, cryodesiccation | Lyophilization is common in pharmaceutical literature. |
| Typical chamber pressure during primary drying | 0.05–0.5 mbar (5–50 Pa) | Must remain below the triple point of water. |
| Typical shelf temperature during freezing | −40 to −20 °C | Lower temperatures may be used for eutectic systems. |
| Typical residual moisture after secondary drying | 0.5–3% w/w | Product-dependent; low moisture improves stability but can cause over-drying. |
| Typical analytical method for residual moisture | Karl Fischer titration or loss on drying | Thermogravimetric methods are also used. |
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.
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.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
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.
As the poisoning progresses, the muscular twitching becomes more pronounced and convulsions suddenly appear in all the skeletal muscles. The limbs are extended and the neck is curved to opisthotonus. The pupils are widely dilated. As death approaches, the convulsions follow one another with increased rapidity, severity, and duration. Death results from asphyxia due to prolonged paralysis of the respiratory muscles. Following the ingestion of strychnine, symptoms of poisoning usually appear within 15 to 60 minutes.
Due to its broad availability, speed, and relatively low cost, it continues to be a common first-line tool in radiologic evaluation. Despite advances in CT, MRI, and other imaging techniques, there are many conditions in which traditional radiographs remain helpful in diagnosis. These include arthritis, pneumonia, bone tumors, fractures, congenital skeletal anomalies, and certain types of kidney stones. Mammography and DXA are two applications of low-energy projectional radiography, used for the evaluation of breast cancer and osteoporosis, respectively.
== History == BioMarin was founded in 1997 by Christopher Starr Ph.D. and Grant W. Denison Jr. with an investment of a $1.5 million from Glyko Biomedical and went public in 1999. Seed investors were amongst others MPM Bioventures, Grosvenor Fund and Florian Schönharting.
Whether that ever means we'll ever play live again, I don't know, especially after Robert's recent [heart attack]." He confirmed that the new album would feature the studio versions of new songs performed by the band between 2014 and 2021, and that "some other bits and pieces will emerge from putting it together. I think so." This news suggests that despite Fripp's 2021 announcement, King Crimson may still be active (albeit as a studio project). In a DGM homepage and Facebook post on 11 July 2025, while suggesting the possibility of "an album the very sound of which no-one has ever heard before. A sound driven by the three drummers," David Singleton both clarified and cautioned speculation about the album. He commented that "it is true that [the three] drummers have now recorded studio versions of their parts – separately, so that there is perfect separation. So there is indeed the seed of a new recording. Whether it is an album, whether it sees the light of day, whether it is something else is unknown. As is the outcome of any creative process. So yes, recordings have taken place. We are building a new studio, and when it is complete I am looking forward to seeing what may, or may not, exist. Getting excited about the possibility of a new album, as has been happening in some quarters, is however somewhat premature. Carts before horses." In a May 2026 interview, Fripp stated that the rumoured new album never came to fruition, that he would not play live again, and that King Crimson's career was over for good.
Sources: en.wikipedia.org
== Medical contributions == Eastlack's home, Philadelphia, has become a center for FOP research with much of it concentrated at the University of Pennsylvania. With his skeleton on display, doctors and professors alike lead students to the Mütter Museum to observe the result of the rare disorder in person. Since surgeries and examinations of FOP patients exacerbate the condition, the ability to study Eastlack's skeleton has been significant for research. For example, in 2006, University of Pennsylvania's team of researchers and scientists led by Frederick Kaplan was able to distinguish the particular gene responsible for the disease, the ACVR1 gene. It is said that Eastlack's skeleton was a useful reference for this medical discovery. The International FOP Association is also granted Eastlack's skeleton for displaying and informational purposes in medical meetings and international FOP symposia, which physicians, researchers, and patients attend. For example, over 43 families were recorded to have attended a two-day symposium hosted in Philadelphia in October 1995 to listen to orthopedic surgeons and physicians discuss the details of FOP. During this symposium, Eastlack's skeleton was used as a reference. After seeing his skeleton at this event, fellow FOP patient Carol Orzel decided to also donate her body to the museum. She died in February 2018, and in February 2019, her skeleton was put on display next to his.
=== Cancer === PAHs have been linked to skin, lung, bladder, liver, and stomach cancers in well-established animal model studies. Specific compounds classified by various agencies as possible or probable human carcinogens are identified in the section "Regulation and Oversight" below.
==== September ==== On 1 September, the National Guard attacked the Walgha, Al-Majdal and Al-Mazraa fronts with a drone, then the Internal Security Forces clashed with the National Guard, leaving 10 members of the Internal Security Forces injured, conversely, the National Guard claimed that the Internal Security Forces launched mortar rounds and fired machine guns. On 4 September, groups considered as "outlaws" forced the expulsion of Atef Hneidi, known as "al-Basha", from the Suwayda governorate, this comes after Atef Hneidi issued a statement criticizing Hikmat al-Hijri. On 6 September, clashes broke out between the National Guard and the Syrian government forces, in the villages of Rima Hazem and Al-Mansoura, involving the use of heavy machine guns. On 10 September, Syrian state television reported that "criminal groups" blocked the al-Matouna checkpoint, meanwhile, a source in Suwayda claimed that Syrian internal security forces stationed in al-Matouna blocked the passage of tourists to Damascus without any explanation. On 24 September, Syrian government forces opened fire with machine guns on the city of Suwayda, and the National Guard responded to the attacks.
==== Increasing mandatory tests in California ==== Many rare diseases have not historically been tested for or testing that has been available has not been mandatory. One such disease is glutaric acidemia type I, a neurometabolic disease present in approximately 1 out of every 100,000 live births. A short-term California testing pilot project in 2003 and 2004 demonstrated the cost of forgoing rare disease testing on newborns. While both Zachary Wyvill and Zachary Black were both born with the same disease during the pilot program, Wyvill's birth hospital tested only for four state-mandated diseases while Black was born at a hospital participating in the pilot program. Wyvill's disease went undetected for over six months during which irreversible damage occurred but Black's disease was treated with diet and vitamin supplements. Both sets of parents became advocates for expanded neonatal testing and testified in favor of expanding tandem mass spectrometry (MS/MS) testing of newborns for rare diseases. By August, 2004, the California state budget law had passed requiring the use of tandem mass spectroscopy to test for more than 30 genetic illnesses and provided funding. California now mandates newborn screening for all infants and tests for 80 congenital and genetic disorders.
== Medical uses == Fixed dose combination of flupentixol and melitracen is indicated for the treatment of anxiety, depression, asthenia, neurasthenia, masked depression, psychosomatic affections accompanied by anxiety and apathy, menopausal depressions, and dysphoria or depression in alcoholics and drug addicts. and is primarily indicated for the following medical uses:
Sources: en.wikipedia.org
=== April === 3 April – Ted Hipkiss, cricketer (Northern Districts) (born 1947). 5 April Raymond Hawthorne, actor (Mortimer's Patch, Bread and Roses, Shortland Street) and theatre director (Mercury Theatre, National Opera of New Zealand) (born 1936). Di McCarthy, behavioural neuroscientist (University of Auckland), chief executive of the Royal Society of New Zealand Te Apārangi (2007–2014). 6 April Sue Berry, physiotherapist and businesswoman, co-founder of Whitestone Cheese (1987) (born 1944). Avis Fletcher, Olympic hurdler and sprinter (1964), British Empire and Commonwealth Games double bronze medallist (1962) (born 1938). 9 April Nancy Carr, home economist (University of Otago) (born 1936). John Mayhew, sports physician (All Blacks, North Harbour, New Zealand Warriors) (born 1954). 11 April – Robyn Kahukiwa, artist, children's writer and illustrator, Te Tohu mō Te Arikinui Dame Te Atairangikaahu (2020) (born 1938). 13 April John Bradshaw, geologist (University of Canterbury), Fellow of the Royal Society of New Zealand (since 1999) (born 1939). David Kernohan, architect and academic (Victoria University of Wellington) (born 1947). 14 April – Peter Matheson, theologian (University of Otago) (born 1938). 16 April – Roger McLachlan, rock bassist (Little River Band) (born 1954). 18 April – Bill Woods, local politician and community leader, Mayor of Selwyn (1992–1995) (born 1942). 19 April – Peter Hilt, politician, MP for Glenfield (1990–1996) (born 1942).
Sucrose gradient centrifugation—a linear concentration gradient of sugar (typically sucrose, glycerol, or a silica-based density gradient media, like Percoll)—is generated in a tube such that the highest concentration is on the bottom and lowest on top. A protein sample is then layered on top of the gradient and spun at high speeds in an ultracentrifuge. This causes heavy macromolecules to migrate towards the bottom of the tube faster than lighter material. During centrifugation in the absence of sucrose, as particles move farther and farther from the center of rotation, they experience more and more centrifugal force (the further they move, the faster they move). The problem with this is that the useful separation range within the vessel is restricted to a small observable window. Spinning a sample twice as long does not mean the particle of interest will go twice as far; in fact, it will go significantly further. However, when the proteins are moving through a sucrose gradient, they encounter liquid of increasing density and viscosity. A properly designed sucrose gradient will counteract the increasing centrifugal force so the particles move in close proportion to the time they have been in the centrifugal field. Samples separated by these gradients are referred to as "rate zonal" centrifugations. After separating the protein/particles, the gradient is then fractionated and collected. In biochemistry, ultracentrifugation is valuable for separating biomolecules and analyzing their physical properties.
== Recent developments == Improvements in structural alignment methods constitute an active area of research, and new or modified methods are often proposed that are claimed to offer advantages over the older and more widely distributed techniques. A recent example, TM-align, uses a novel method for weighting its distance matrix, to which standard dynamic programming is then applied. The weighting is proposed to accelerate the convergence of dynamic programming and correct for effects arising from alignment lengths. In a benchmarking study, TM-align has been reported to improve in both speed and accuracy over DALI and CE. Other promising methods of structural alignment are local structural alignment methods. These provide comparison of pre-selected parts of proteins (e.g. binding sites, user-defined structural motifs) against binding sites or whole-protein structural databases. The MultiBind and MAPPIS servers allow the identification of common spatial arrangements of physicochemical properties such as H-bond donor, acceptor, aliphatic, aromatic or hydrophobic in a set of user provided protein binding sites defined by interactions with small molecules (MultiBind) or in a set of user-provided protein–protein interfaces (MAPPIS). Others provide comparison of entire protein structures against a number of user submitted structures or against a large database of protein structures in reasonable time (ProBiS).
An evaporative light scattering detector (ELSD) is a destructive chromatography detector, used in conjunction with high-performance liquid chromatography (HPLC), ultra high-performance liquid chromatography (UHPLC), purification liquid chromatography such as flash or preparative chromatography (using a splitter), countercurrent or centrifugal partition chromatography and supercritical fluid chromatography (SFC). It is commonly used for analysis of compounds that do not absorb UV-VIS radiation significantly, such as sugars, antiviral drugs, antibiotics, fatty acids, lipids, oils, phospholipids, polymers, surfactants, terpenoids and triglycerides. ELSDs works by nebulizing the column's effluents into a fine aerosol mist, which then passes through a heated drift tube, where the solvent evaporates. Thus, it can be easily used in gradient method of LC and SFC. The remaining non-volatile analyte particles are carried further by a carrier gas to a light scattering cell, where a beam of light illuminates them and they scatter it. The scattered light proceeds to a photodiode which converts it to a signal, which is proportional to the mass of the analyte particles. This is why it is considered as a sort of "universal detector" as it is able to detect all compound which are less volatile than the mobile phase, i.e. non volatile and semi-volatile compounds. ELSD is related to the charged aerosol detector (CAD), in which the aerosol is charged. Like the CAD, it falls under the category of destructive detectors.
=== Genoa === In September 2021, 777 Partners bought 99.99% of Italian Serie A club Genoa CFC, the country's oldest club, founded in 1893. It became the sixth club in the league to have an American owner, and the transaction to buy the club from long-term owner Enrico Preziosi was estimated at €150 million. The club hired former AC Milan and Ukraine striker Andriy Shevchenko as the club manager in November, firing him in January 2022; Genoa ended the season relegated (as did another US-owned team, Venezia FC), but were immediately promoted back into the top division in May 2023. James Horncastle wrote in May 2024 that Genoa fans were not antagonistic toward 777, partly due to a history of mismanagement by Preziosi. Horncastle mentioned that Genoa had a one-point deduction for a late tax payment in their 2022–23 Serie B promotion season. On 18 December 2024, Genoa CFC announced that new majority stakeholder Dan Șucu, a Romanian businessman and owner of FC Rapid București and Mobexpert had taken over the club by paying €45m for 77% of the club. The following day, A-CAP released a statement advising that they still own the club, however, the board of Genoa CFC maintains that the sale is final.
Sources: en.wikipedia.org
Yes, the terms are generally interchangeable. Lyophilization is more common in pharmaceutical and laboratory contexts, while freeze-drying appears widely in food science and general writing. Both describe removal of solvent by sublimation under vacuum after freezing.
Reduced pressure keeps the process below the triple point of water, so ice can sublimate directly to vapor. It also lowers the temperature needed for drying, which helps preserve heat-sensitive materials. Without vacuum, melting or boiling could occur instead of controlled sublimation.
The rate depends on heat transfer to the product and mass transfer of vapor through the dried layer. A cold condenser, adequate vacuum, and suitable shelf temperature all influence speed. Formulation properties such as solid content and collapse temperature also set practical limits.
Lyophilization relies on sublimation, so water moves from solid ice to vapor without becoming liquid. The material is frozen, pressure is reduced, and controlled heat is supplied. Vapor is captured on a cold condenser, leaving a dry porous solid.