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 2026-04-06 and is reviewed periodically as new material appears.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
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 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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
Lyophilization, also called freeze-drying, removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts free water into ice and may also produce a glassy phase. Primary drying then lowers chamber pressure so ice sublimes directly to vapor without passing through a liquid stage. Secondary drying raises the temperature modestly to remove bound water. The result is a porous, dry solid that usually reconstitutes quickly. Each stage influences pore structure, residual moisture, and stability.
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
Equipment for lyophilization includes a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. A refrigeration system cools the shelves and condenser below the product's freezing point. Process monitoring often uses Pirani and capacitance manometers, thermocouples, and resistance sensors. Cycle development balances product quality with time and energy use. Some products are annealed during freezing to improve crystallization of bulking agents. Open questions remain about scaling cycles between laboratory, pilot, and production freeze-dryers.
Formulation composition influences whether freeze-drying produces an intact cake or a collapsed mass. Excipients such as sugars and polymers can raise the collapse temperature and provide bulk during drying. The critical temperature for primary drying is often the collapse temperature or the glass transition temperature of the maximally concentrated phase. If the product temperature exceeds this threshold, the frozen matrix may soften and lose structure. Established practice therefore links shelf temperature and chamber pressure to the formulation's thermal properties.
The physics of freeze-drying couples heat transfer, mass transfer, and phase change. Heat supplied through the shelf must reach the sublimation front without melting the ice or degrading the product. Water vapor then travels through the already dried layer and leaves the chamber, where low pressure and cold traps keep it from returning. The dried layer acts as a resistance to vapor flow, so drying rate changes as the front recedes. Open questions remain about how pore structure and formulation heterogeneity affect drying uniformity at larger scales.
Freeze-drying is used for materials whose activity or structure depends on low temperature and low water content. Examples include certain biologics, diagnostic reagents, starter cultures, coffee, and porous inorganic precursors. The dried product forms a cake whose porosity aids rapid wetting and dissolution. Main drawbacks are high energy use, long cycle times, and sensitivity to formulation and equipment variation. Questions remain about how freezing rates and ice morphology affect batch uniformity, especially when moving from laboratory to production scale.
Lyophilization, also called freeze-drying, is a dehydration process in which a solvent, usually water, is frozen and then removed by sublimation under reduced pressure. The method preserves heat-sensitive materials that would degrade in conventional drying. Large-scale use grew during the mid-twentieth century for blood plasma and antibiotics, and it later expanded to vaccines, enzymes, foods, and advanced materials. The process produces a dry, porous solid that usually reconstitutes rapidly. It is distinct from simple evaporation because the solvent bypasses the liquid phase during primary removal.
The process generally proceeds in three stages: freezing, primary drying, and secondary drying. During freezing, controlled cooling converts water into ice and may also crystallize or vitrify solutes. In primary drying, the pressure is lowered below the triple point, and heat is supplied so ice sublimes directly to vapor. Secondary drying removes water that remains bound to the solid matrix, yielding a low final water content. Product temperature must stay below the collapse or glass transition temperature to maintain structure. Cycle design therefore balances shelf temperature, chamber pressure, and time.
The aim is to come up with tools that can pre-screen patients with four tumour types for the MSI-H biomarker, namely endometrial, gastric, small intestinal, and biliary cancers. In January 2024, the company announced it would acquire Harpoon Therapeutics for $680 million. With this purchase, Merck expands its portfolio of oncological drugs. The main positions are HPN328, an activator of T-cells that is being researched to treat advanced cancer patients associated with DLL3 expression (delta-like ligand 3), an inherent small cell lung cancer (SCLC), neuroendocrine tumors, and several other species. Merck's portfolio will also be complemented by T-cell attractions using the patented Harpoon Tri-specific design for T cell activation (TriTAC). According to engineering protein technology, tumor cells are destroyed by the patient's own immune cells, and the ProTriTAC platform works with the TriTAC platform to develop a therapeutic agent that attracts T-cells, but is inactive until it reaches the tumor. In April 2024, Merck completed the acquisition of Abceutics for $208 million. In July 2024, Merck completed the acquisition of EyeBio for $3 billion. In October 2024, Merck announced the acquisition of Modifi Biosciences for $1.3 billion. In January 2026, the Wall Street Journal reported that Merck was in talks to acquire Revolution Medicines for ~$30 billion.
=== Recreational use === As a μ-opioid agonist, tianeptine in large doses has high abuse potential. In 2001, Singapore's Ministry of Health restricted tianeptine prescribing to psychiatrists due to its recreational potential. Between 1989 and 2004, in France 141 cases of recreational use were identified, correlating to an incidence of 1 to 3 cases per 1000 persons treated with tianeptine and 45 between 2006 and 2011. According to Servier, stopping of treatment with tianeptine is difficult, due to the possibility of withdrawal symptoms. The severity of the withdrawal is dependent on the daily dose, with high doses being extremely difficult to quit. An official DEA statement states that the withdrawal symptoms in humans typically result in: agitation, nausea, vomiting, tachycardia, hypertension, diarrhea, tremor, and diaphoresis, similar to other opioid drugs. In 2007, according to French Health Products Safety Agency, tianeptine's manufacturer Servier agreed to modify the drug's label, following problems with dependency. Tianeptine has been intravenously injected by drug users in Russia. This method of administration reportedly causes an opioid-like effect and is sometimes used in an attempt to lessen opioid withdrawal symptoms. Tianeptine tablets contain silica and do not dissolve completely. Often the solution is not filtered well thus particles in the injected fluid block capillaries, leading to thrombosis and then severe necrosis.
At 19:10, Xi, wearing a Chinese tunic suit, and Peng, who wore a long-sleeved V-neck gown in red, returned to the White House for a state dinner, where Trump and his wife greeted them. As the state banquet was held close to the Mid-Autumn Festival, the White House arranged the song "The Moon Represents My Heart" as the entrance music. The dinner was planned by First Lady Melania Trump and consisted of American dishes with subtle Chinese influence. Schramsberg “Blanc De Noir” was chosen for the toast, honoring the "Toast of Peace" shared between President Richard Nixon and Premier Zhou Enlai in 1972. Tables were covered with bright red linens and were adorned with red candles and flower arrangements of red dahlias and ranunculus, while guests ate off red tablecloths; red is a symbol of luck and good fortune in Chinese culture. A three‑course meal of yellow squash velouté, sesame crusted sea bass, and vanilla crémeux & White House honey ice cream was served at the dinner. The dinner was accompanied by musical performances by Christopher Macchio, the United States Marine Band, the United States Marine Drum and Bugle Corps, the United States Army Chorus, and the United States Army Strings. Other members of the Chinese delegation, including Cai Qi and Wang Yi, wore Chinese tunic suits like Xi; while it is common for the Chinese leader to wear such a suit in state dinners, other members of the Chinese delegation usually wore Western suits in other occasions.
Sources: en.wikipedia.org
== Regulation == In Europe, regulation is currently split into three areas of regulation: medical devices, medicinal products, and biologics. Tissue engineering products are often of hybrid nature, as they are often composed of cells and a supporting structure. While some products can be approved as medicinal products, others need to gain approval as medical devices. Derksen explains in her thesis that tissue engineering researchers are sometimes confronted with regulation that does not fit the characteristics of tissue engineering. New regulatory regimes have been observed in Europe that tackle these issues. An explanation for the difficulties in finding regulatory consensus in this matter is given by a survey conducted in the UK. The authors attribute these problems to the close relatedness and overlap with other technologies such as xenotransplantation. It can therefore not be handled separately by regulatory bodies. Regulation is further complicated by the ethical controversies associated with this and related fields of research (e.g. stem cells controversy, ethics of organ transplantation). The same survey as mentioned above shows on the example of autologous cartilage transplantation that a specific technology can be regarded as 'pure' or 'polluted' by the same social actor. Two regulatory movements are most relevant to tissue engineering in the European Union.
the tenor of the time had generally turned against... outlandishness and people had mostly returned to looking more like people over the last millennium... (previously) as the fashions of the intervening times had ordained – people... had resembled birds, fish, dirigible balloons, snakes, small clouds of cohesive smoke and animated bushes. Some Culture citizens opt to leave the constraints of a human or even humanoid body altogether, opting to take on the appearance of one of the myriad other galactic sentients (perhaps in order to live with them) or even non-sentient objects as commented upon in Matter (though this process can be irreversible if the desired form is too removed from the structure of the human brain). Certain eccentrics have chosen to become drones or even Minds themselves, though this is considered rude and possibly even insulting by most humans and AIs alike. While the Culture is generally pan-humanoid (and tends to call itself "human"), various other species and individuals of other species have become part of the Culture. As all Culture citizens are of perfect genetic health, the very rare cases of a Culture citizen showing any physical deformity are almost certain to be a sort of fashion statement of somewhat dubious taste.
White sharks communicate with each other through a complex array of body language. Most behaviors have been observed at aggregations around seal rookeries shortly after peak hunting periods, where sharks engage in extensive socializing. At least 20 unique forms of body language are known, most of which consist of two sharks swimming in passing, parallel, or circular patterns to ritualistically examine one another. Occasionally, one shark will openly show off its body in a lateral display to the other. It is hypothesized that the main purpose of these interactions is to establish social rank by size to avoid competition. Observations by Sperone and colleagues in 2010 found display behaviors to be more common between individuals of similar size where differences are not immediately obvious. There is no evidence that sex is a significant factor in behavioral patterns. With dominance established, the smaller shark then acts submissively towards the larger shark by yielding during subsequent encounters or simply avoiding confrontation. Body language is less frequent in California and Australia compared to Dyer Island in South Africa. It is thought that this is because the former locations are less densely populated, and so sharks there are more familiar with each other's hierarchy. Direct violence is extremely rare, as individuals typically end conflicts through peaceful means. Splash fights appear to be the most common way of resolving ownership disputes over prey. Here, one shark slaps the surface with its tail to splash water at the competing shark.
Sources: en.wikipedia.org
The second head of the institute was Alexander Bogomolets (see further). 1930s Beginning of attempts of rejuvenation by methods of cell injections. A special role belongs here to the Swiss physician Paul Niehans – he was not the first but he was the one who developed this approach the most. Among his patients there were many famous people (including Winston Churchill, Charles de Gaulle, Pope Pius XII). So, in 1952, about 3000 injections of about 10 cm3 of cell suspension were reported. As a consequence, cell therapy and regenerative medicine were formed. Since the 1960s, attempts have been made to inject not only whole cells but also their constituent parts (such as isolated DNA and RNA). But usage of embryonic drugs sometimes caused serious complications, so the American association of physicians recognized the method of cell therapy as dangerous. 1930 The first world's journal about aging and longevity. It was established in Japan and has the name Acta Gerontologica Japonica (Yokufuen Chosa Kenkyu Kiyo). 1933 The first institute in the world dedicated to study of aging. It was created in Kishinev (at that time inside the Kingdom of Romania) by Dimu Kotsovsky. Initially the institute was maintained by his own means, and was subsequently recognized by the Romanian government. The name is Romanian: Institutul Pentru Studierea si Combaterea Batranetii = German: Institut für Altersforschung und Altersbekämpfung = Institute for The Study and Combat of Aging.
== Personal life == He married Margaret (Jennie) Jenkins and had two sons, Paul and Simon. Following the death in 1976 of his son Paul, guitarist with the band Free and later with Back Street Crawler, Kossoff established the Paul Kossoff Foundation which aimed to present the realities of drug addiction to children. Kossoff spent the remainder of his life campaigning against drugs. In the late 1970s and early 1980s, he toured with a one-man stage performance about the death of his son and its effect on the family. He died in 2005 of liver cancer at age 85. In its obituary, The Scotsman wrote that David Kossoff was "a man of deep convictions and proud of his Jewish origins".
Phthalates have been banned from use in feeding bottles in the EU. In the US, there have been repeated calls for the removal of phthalates by the U.S. Consumer Product Safety Commission (CPSC) and others. Their use in children's toys and products was somewhat restricted by the Consumer Product Safety Improvement Act of 2008. Plastics labeled #3 may leach phthalates. Latex rubber nipples may contain phthalates, so silicone nipples may be recommended instead. Packaging may indicate whether a product is "BPA-free" or "phthalate-free". Plastics may degrade over time in other ways, There are concerns that small beads of plastic may be released into fluids from some types of plastic bottles. In 2020 researchers reported that infant feeding bottles made out of polypropylene caused microplastics exposure to infants ranging from 14,600 to 4,550,000 particles per capita per day in 48 regions with contemporary preparation procedures. Microplastics release is higher with warmer liquids and similar with other polypropylene products such as lunchboxes. In 2022, the first study to examine the presence of plastic polymers in human blood found plastics of multiple types in the blood samples of 17 out of 22 healthy adults tested (nearly 80%). Medical experts have suggested reducing exposure to microplastics by not shaking plastic bottles or exposing them to high temperatures. Some recommend using alternative materials such as glass, silicone, or stainless steel.
== Awards and affiliations == Smith a principal investigator at NIH Biomedical Technology Resource Center for Integrative Biology and the U.S. Department of Energy High Throughput Proteomics Facility at PNNL. He is an adjunct faculty member in the chemistry departments at Washington State University and the University of Utah and an affiliate faculty member Department of Chemistry at the University of Idaho and the Department of Molecular Microbiology & Immunology, Oregon Health & Science University. Smith serves on the Board of Scientific Counselors, Office of Public Health Preparedness and Response of the Centers for Disease Control and Prevention. He is also a Fellow of the American Association for the Advancement of Science, and has been elected to the Washington State Academy of Sciences. In 2011, Discover Magazine selected a peer-reviewed paper on Lyme disease that he coauthored with immunologist Steven Schutzer of the University of Medicine and Dentistry of New Jersey as one of the top 100 articles of the year, placing it at number 90. He was the recipient of the 2003 ACS award in Analytical Chemistry, the 2009 Human Proteome Organization (HUPO) Discovery Award in Proteomics Sciences, and was selected by R&D Magazine as the 2010 R&D Scientist of the Year.
Sources: en.wikipedia.org
The main change is sublimation, in which ice becomes water vapor without melting into liquid water. This occurs when the chamber pressure is held below the vapor pressure of ice while mild heat is supplied. The result is a dry, porous solid that retains much of its original shape.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
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.