This is a working overview of Sublimation, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-10-06. Anything still debated is marked as such rather than presented as settled.
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.
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.
Quality control for freeze-dried lots combines visual inspection with instrumental tests. Cake appearance, color, and shrinkage are recorded against a reference, while residual moisture is measured by Karl Fischer titration or loss on drying. Thermal analysis can reveal phase transitions and crystallization events, and X-ray diffraction distinguishes amorphous from crystalline solids. Microbiological tests and container closure integrity checks are also routine for sterile products. Analytical methods must be validated for the matrix, because excipients and low moisture can affect accuracy. Open questions include how best to predict long-term stability from short-term data.
Lyophilized solids are often hygroscopic, so handling occurs in controlled low-humidity areas or glove boxes when the material is exposed. Vials remain sealed with elastomeric stoppers and aluminum crimps until use, because airborne moisture can raise residual water and shorten shelf life. The porous cake is fragile and may crack, shrink, or powder during transport. Personnel typically avoid repeated warming and cooling of sealed units, which can draw moisture through closures. These practices aim to preserve the low water content achieved during 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. |
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.
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.
In 1954, Mogens Schou of Denmark confirmed lithium's efficacy in a randomzied double-blind placebo-controlled study with his colleagues. Schou and Paul Baastrup organized other studies over the following years and decades and published a variety of research papers about lithium. At the time, lithium was a major advance. Before the advent of lithium, barbiturates were the standard treatment for mania. However, lithium was met with great resistance by British psychiatry. To Aubrey Lewis and Michael Shepherd, from the Institute of Psychiatry at Maudsley Hospital, lithium was ‘dangerous nonsense’. Michael Shepherd and Barry Blackwell called lithium a 'therapeutic myth.' The Maudsley psychiatrists had a history of debunking ineffective medical treatments. They claimed that Schou was biased because his brother, who experienced recurrent depressions since childhood, had a dramatic response to lithium. Schou felt that it had cured him. Largely through the research and other efforts of Mogens Schou and Paul Baastrup in Europe, and Samuel Gershon and Baron Shopsin in the U.S., resistance to lithium was slowly overcome. The American Psychiatric Association (APA) established a lithium task force chaired by Irvin M. Cohen, with members William Bunney, Jonathan Cole, Ronald R. Fieve, Samuel Gershon, Robert Prien, and Joseph Tupin. The recommendation of the lithium task force was to approve lithium. The application of lithium in manic illness was approved by the Food and Drug Administration in 1970, becoming the 50th nation to do so.
== Kinase activity == A kinase is a type of enzyme that transfers phosphate groups (see below) from high-energy donor molecules, such as ATP (see below) to specific target molecules (substrates); the process is termed phosphorylation. The opposite, an enzyme that removes phosphate groups from targets, is known as a phosphatase. Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases.
=== Names === Ritanserin is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name. It is also known by its developmental code name R-55667.
With the merger of the laboratories into a single entity, the history offices at each site ceased to maintain independent histories and all history functions were transferred to a central History Office located at AFRL HQ at Wright-Patterson AFB. In homage to the predecessor laboratories, the new organization named four of the research sites after the laboratories and assured that each laboratory's history would be preserved as inactivated units. In 2023, the National Advanced Air Mobility Center of Excellence was completed to help the Laboratory, private companies, and local academics collaborate on the research of eVTOL and UAS aircraft.
On March 28, 2013, a team of bioengineers from Stanford University led by Drew Endy announced that they had created the biological equivalent of a transistor, which they named a "transcriptor". That is, they created a three-terminal device with a logic system that can control other components. The transcriptor regulates the flow of RNA polymerase across a strand of DNA using special combinations of enzymes to control movement. According to project member Jerome Bonnet, "The choice of enzymes is important. We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms." Transcriptors can replicate traditional AND, OR, NOR, NAND, XOR, and XNOR gates with equivalents, which Endy dubbed "Boolean Integrase Logic (BIL) gates", in a single-layer process (i.e., without requiring multiple instances of the simpler gates to build up more complex ones). Like a traditional transistor, a transcriptor can amplify an input signal. A group of transcriptors can do almost any type of computing, including counting and comparison.
Sources: en.wikipedia.org
Some groups of people have specialized transfusion requirements. Fetuses, very low-birth-weight infants, and immunocompromised people are at risk for developing severe infection with cytomegalovirus (CMV)―an opportunistic pathogen for which approximately 50% of blood donors test positive―and may be transfused with CMV-negative blood to prevent infection. Those who are at risk of developing graft-versus-host disease, such as bone marrow transplant recipients, receive blood that has been irradiated to inactivate the T lymphocytes that are responsible for this reaction. People who have had serious allergic reactions to blood transfusions in the past may be transfused with blood that has been "washed" to remove plasma. The history of the patient is also examined to see if they have previously identified antibodies and any other serological anomalies. A direct antiglobulin test (Coombs test) is also performed as part of the antibody investigation. Donor blood is generally screened for transfusion-transmitted infections such as HIV. As of 2018, the World Health Organization reported that nearly 100% of blood donations in high- and upper-middle-income countries underwent infectious disease screening, but the figures for lower-middle-income and low-income countries were 82% and 80.3% respectively.
One more very convincing experiment from Dubna was published in 1966 (though it was submitted in 1965), again using the same two reactions, which concluded that 254No indeed had a half-life much longer than the 3 seconds claimed by Berkeley. Later work in 1967 at Berkeley and 1971 at the Oak Ridge National Laboratory fully confirmed the discovery of element 102 and clarified earlier observations. In December 1966, the Berkeley group repeated the Dubna experiments and fully confirmed them, and used this data to finally assign correctly the isotopes they had previously synthesized but could not yet identify at the time. Thus they claimed to have discovered nobelium in 1958 to 1961.
29 November Astronomers report the discovery of a star, HD 110067, that contains six sub-Neptune exoplanets with radii ranging from 1.94R⊕ to 2.85R⊕. The first example of a planet-forming disk beyond the Milky Way galaxy is reported by astronomers using the ALMA in Chile. The system, designated as HH 1177, is located in the Large Magellanic Cloud, about 160,000 light years away. 30 November Researchers demonstrate multicellular microbots grown from a human cell, "anthrobots", that can move around in tissues in vitro. A trial comparing a healthy vegan and a healthy omnivorous diet in identical twins finds the former to be substantially better according to cardiometabolic measures like LDL-C after 8 weeks. Promising innovations relating to global challenges are reported: an efficient electrocaloric heat pump for sustainable cooling (16 Nov), taste-tested bioreactor-grown cultured coffee (17 Nov), an autonomous laboratory for synthesis of inorganic powders, the A-Lab (29 Nov), a solar tower design using downdraft technology for hot and dry weather areas that could generate twice the electricity of solar updraft systems and operate at night, the Twin-Technology Solar System (TTSS) (30 Nov). Promising results of health and medical research are reported: phase 2-trialed Mazdutide against type-2 diabetes (9 Nov), phase 1-trialed lepodisiran against cardiovascular risk factor lipoprotein (12 Nov), rat-tested depot technology for sustained delivery of GLP-1 receptor agonists against the need for frequent injections (21 Nov).
=== Biochemistry === In solution, detergents help solubilize a variety of chemical species by dissociating aggregates and unfolding proteins. Popular surfactants in the biochemistry laboratory are sodium lauryl sulfate (SDS) and cetyl trimethylammonium bromide (CTAB). Detergents are key reagents to extract protein by lysis of the cells and tissues: they disorganize the membrane's lipid bilayer (SDS, Triton X-100, X-114, CHAPS, DOC, and NP-40), and solubilize proteins. Milder detergents such as octyl thioglucoside, octyl glucoside or dodecyl maltoside are used to solubilize membrane proteins such as enzymes and receptors without denaturing them. Non-solubilized material is harvested by centrifugation or other means. For electrophoresis, for example, proteins are classically treated with SDS to denature the native tertiary and quaternary structures, allowing the separation of proteins according to their molecular weight. Detergents have also been used to decellularise organs. This process maintains a matrix of proteins that preserves the structure of the organ and often the microvascular network. The process has been successfully used to prepare organs such as the liver and heart for transplant in rats. Pulmonary surfactants are also naturally secreted by type II cells of the lung alveoli in mammals.
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.
Karl Fischer titration is widely used because it is specific for water and works at low levels. Loss on drying is simpler but less specific, since volatile solvents or decomposition products can also be lost.