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 2026-04-19 and is reviewed periodically as new material appears.
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.
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.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and concentrates dissolved solids. Primary drying then lowers chamber pressure so ice changes directly into vapor without passing through a liquid phase. Secondary drying raises the shelf temperature to remove bound water that remains after ice sublimation. The result is a dry, porous structure that can be reconstituted later.
| 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 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 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.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen to convert liquid water into ice. Next, the pressure is reduced below the triple point of water so that ice changes directly into vapor without passing through a liquid phase. This step is called primary drying. The result is a porous solid or cake that retains the original shape of the frozen solution.
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.
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.
== Medical uses == Dielectric heating (diathermy) is used in medicine; the frequencies used typically lie in the ultrasonic, shortwave, and microwave ranges. Careless application, especially when the patient has implanted metal conductors (e.g. cardiostimulator leads), can cause burns of skin and deeper tissues and even death. Microwave damage to tissues can be intentionally exploited as a therapeutic technique, e.g. radiofrequency ablation and radiofrequency lesioning. Controlled destruction of tissue is performed for treatment of arrhythmia. Microwave coagulation can be used for some kinds of surgeries, e.g., stopping bleeding after a severe liver injury. Microwave heating seems to cause more damage to bacteria than equivalent thermal-only heating. However food reheated in a microwave oven typically reaches lower temperature than classically reheated, therefore pathogens are more likely to survive. Microwave heating of blood, e.g. for transfusion, is contraindicated, as it can cause hemolysis and hyperkalemia. Microwave heating is one of the methods for inducing hyperthermia for hyperthermia therapy. High-energy microwaves are used in neurobiology experiments to kill small laboratory animals (mice, rats) in order to fix brain metabolites without the loss of anatomical integrity of the tissue. The instruments used are designed to focus most of the power to the animal's head. The unconsciousness and death is nearly instant, occurring in less than one second, and the method is the most efficient one to fix brain tissue chemical activity.
=== 2018–present: Business and continued television success === In December 2018, Kardashian became the brand ambassador of Burst Oral Care & performed corn test on the electric toothbrush. On June 14, 2019, Kylie Cosmetics launched their collaboration with Kardashian called Kylie Cosmetics x Koko Kollection. This marked their third collaboration, after previously launched special collection of lip products called Koko Kollection in 2016 and the second part in 2017. In August 2019, Kardashian announced she will become an executive producer for the new season of Twisted Sisters, an Investigation Discovery show, consisting of ten hour-long episodes following stories of sisters who turned on each other. In November 2019, Kardashian partnered with her sisters Kourtney and Kim to create three new perfumes (one for each sister) for Kim's brand KKW Fragrance. The collection introduces Pink Diamond (Khloé's fragrance), Yellow Diamond (Kourtney's fragrance) and pure Diamond (Kim's fragrance). Each scent is individually inspired by and unique to her, Kim, and Kourtney. In October 2020, it was announced she became the brand ambassador and co-owner of Kiwi collagen supplement company Dose & Co. In 2021, Kardashian and her family announced that their reality show, Keeping Up with the Kardashians, would be ending after twenty seasons and almost 15 years on air. In September 2021, Khloe Kardashian hosted a tournament for Candy Crush Saga, marking the game's first tournament. The tournament was held in-app from September 23 until October 7.
== Research directions == The approach of screening the soil for useful compounds using genomics has been done by others, and is likely to continue to be pursued as a method to further explore primary metabolites and secondary metabolites made by microorganisms. As of February 2018, the malacidins had not been tested on humans. At the time of their discovery it was unknown whether the discovery would lead to any new antibiotic drugs; showing that a potential drug is safe and effective takes years of work and millions of dollars, and the scientists said at the time that they had no plans to try to develop a drug based on the work. In the 2018 paper, malacidins were shown to kill only Gram-positive bacteria and not Gram-negative bacteria. They were, however, able to kill multidrug-resistant pathogens, including bacteria resistant to vancomycin in the laboratory, and methicillin-resistant Staphylococcus aureus (MRSA) skin infections in an animal wound model. Brady, Hover, and two other authors disclosed in the 2018 paper that they had "competing financial interests, as they are employees or consultants of Lodo Therapeutics." Lodo was founded in 2016 out of Brady's laboratory, to discover new chemicals in nature as starting points for drug discovery.
== History == Protein rich in phosphate was discovered early on. In 1906, Levene and Alsberg studied cleavage products of yolk vitellin, and showed that a phosphorus-rich proteinaceous fraction could be obtained from it. In 1933, Fritz Lipmann detected phosphoserine in casein. In 1948, a particularly phosphate-rich protein was isolated from yolk, and it was named phosvitin. Phosphorylase enzymes were discovered later. The first phosphorylase enzyme was discovered by Carl and Gerty Cori in the late 1930s. Carl and Gerty Cori found two forms of glycogen phosphorylase which they named A and B but did not correctly understand the mechanism of the B form to A form conversion. In 1954, another enzyme was discovered, which transfers phosphate from ATP onto a protein. Its physiological function was still not known. Glycogen phosphorylation was better understood later. The interconversion of phosphorylase b to phosphorylase a was described by Edmond Fischer and Edwin Krebs involving a phosphorylation/dephosphorylation mechanism. It was found that an enzyme named phosphorylase kinase and Mg-ATP were required to phosphorylate glycogen phosphorylase by assisting in the transfer of the γ-phosphoryl group of ATP to a serine residue on phosphorylase b. Protein phosphatase 1 is able to catalyze the dephosphorylation of phosphorylated enzymes by removing the phosphate group. Sutherland and Coris discovered epinephrine acts by activating phosphorylase, which leads to the formation of glucose from glycogen.
Sources: en.wikipedia.org
The Honeywell 316 was a popular 16-bit minicomputer built by Honeywell starting in 1969. It is part of the Series 16, which includes the Models 116 (1965, discrete), 316 (1969), 416 (1966), 516 (1966) and DDP-716 (1969). They were commonly used for data acquisition and control, remote message concentration, clinical laboratory systems, Remote Job Entry and time-sharing. The Series-16 computers are all based on the DDP-116 designed by Gardner Hendrie at Computer Control Company, Inc. (3C) in 1964. The 516 and later the 316 were used as Interface Message Processors (IMP) for the American ARPANET and the British NPL Network.
Saeed Balalaie (Persian: سعید بلالایی; born 26 September 1965) is an Iranian organic chemist and professor at K. N. Toosi University of Technology. His research focuses on multicomponent reactions, peptide synthesis, and the synthesis of active pharmaceutical ingredients. Balalaie was a recipient of the 33rd Khwarizmi International Award in 2019 (announced in February 2020) for applied research and was named Iran's National Outstanding Researcher in the same year (2019). He has received multiple research fellowships from the Alexander von Humboldt Foundation and served as the foundation's Scientific Ambassador in Iran from 2015 to 2020.
=== Modifiable === Western pattern diet Abdominal obesity Diabetes Dyslipidemia High blood cholesterol High blood pressure Elevated concentrations of apolipoprotein B (ApoB)-containing lipoproteins (such as LDL particles), for which LDL-cholesterol (LDL-C) is the most commonly used surrogate marker High saturated fat diet Trans fat Tobacco smoking Bacterial infections HIV/AIDS Psychological stress Sedentary lifestyle
== Examples == ornithine translocase (SLC25A15), associated with ornithine translocase deficiency. carnitine-acylcarnitine translocase (SLC25A20), associated with carnitine-acylcarnitine translocase deficiency. Translocase of outer mitochondrial membrane 40 (TOMM40), a protein encoded by the TOMM40 gene, whose alleles differentially impact the risk for Alzheimer's disease
serious infections reactivation of hepatitis B reactivation of tuberculosis lethal hepatosplenic T-cell lymphoma (generally only when combined with 6-mercaptopurine) drug-induced lupus demyelinating central nervous system disorders psoriasis and psoriasiform skin lesions new-onset vitiligo Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported with infliximab. The FDA issued a warning to doctors appearing in the respective product labeling of infliximab instructing them to screen and monitor potential patients more carefully. The FDA issued a warning to doctors that there is an increased risk of lymphoma and other cancers associated with the use of infliximab and other tumor necrosis factor blockers in children and adolescents. Maintenance therapy with the drug (versus intermittent or sporadic therapy) lessens the likelihood of developing antibodies to infliximab which are known to reduce the efficacy of the drug. Combination treatment with methotrexate (an antifolate drug which suppresses the immune system) has been shown to reduce the formation of these antibodies in patients with rheumatoid arthritis and combination therapy with other immunosuppressants has been shown to reduce the likelihood of these antibodies being formed in Crohn's disease. The use of immunosuppressants may not be necessary in all diseases for which infliximab is indicated, and indiscriminant uses of these other immunosuppressants carry their own risks.
Sources: en.wikipedia.org
==== Re-sentencing of death row inmates ==== The amendments of the law also offered a chance for all current death row inmates to have their cases to be reviewed for re-sentencing. Some death row inmates declined to be re-sentenced, including Tang Hai Liang and Foong Chee Peng. The below cases are known cases where death row inmates applied for re-sentencing.
In multiple electrode aggregometry, anticoagulated whole blood is mixed with saline and a platelet agonist in a single-use cuvette with two pairs of electrodes. The increase in impedance between the electrodes as platelets aggregate onto them, is measured and visualized as a curve.
Kenney, Padraic. 1989: Democratic Revolutions at the Cold War's End: A Brief History with Documents (2009) covers Poland, the Philippines, Chile, South Africa, Ukraine, and China Leffler, Melvyn P. For the Soul of Mankind: The United States, the Soviet Union, and the Cold War (2007) pp 338–450. Mann, James. The Rebellion of Ronald Reagan: A History of the End of the Cold War (2010). popular Matlock, Jack F. Autopsy on an Empire (1995) online by US ambassador to Moscow Matlock, Jack F. Reagan and Gorbachev : how the Cold War ended (2004) online Powaski, Ronald E. The Cold War: The United States and the Soviet Union, 1917–1991 (1998) Romero, Federico. "Cold War historiography at the crossroads." Cold War History 14.4 (2014): 685–703. online Shultz, George P. Turmoil and Triumph: My Years as Secretary of State (1993), a primary source Wilson, James Graham. The Triumph of Improvisation: Gorbachev's Adaptability, Reagan's Engagement, and the End of the Cold War (2014) Wohlforth, William C. "Realism and the End of the Cold War." International Security 19.3 (1994): 91–129. online Zubok, Vladislav M. "Gorbachev and the End of the Cold War: Perspectives on History and Personality," Cold War History (2002) 2:2, 61–100, DOI: 10.1080/713999954 Zubok, Vladislav M. A failed empire: the Soviet Union in the Cold War from Stalin to Gorbachev (2009). online Archived 2020-09-19 at the Wayback Machine
On July 9, Trump reversed a previously suspended military aid package to Ukraine following Russia's largest aerial assault on the country, involving hundreds of drones and missiles. The suspension, reportedly authorized by senior defense officials without Trump's prior knowledge. Trump expressed growing frustration with Russian president Vladimir Putin, accusing him of insincerity and relentless aggression, saying, "He wants to go all the way, just keep killing people, it's no good." The U.S. are discussing sending 10 Patriot missiles to Ukraine, and Trump said he is reviewing a proposed sanctions bill by Senator Lindsey Graham that would impose 500% tariffs on countries trading with Russia. Although Trump has previously mentioned secondary sanctions, none have been implemented so far, with the president citing their cost and waiting to see if a peace deal would emerge. On July 14, 2025, Trump threatened to impose 100% tariffs and secondary sanctions on countries purchasing Russian oil if Russia did not agree to a ceasefire within 50 days. Trump confirmed a summit meeting between him and Putin to be held on August 15, 2025, in Alaska The high-level summit at Joint Base Elmendorf–Richardson in Anchorage concluded without progress toward a ceasefire. Following the talks, Trump suggested the United States could assist Ukraine with surveillance flights or air defense support, while ruling out the deployment of ground troops.
Early blood culture methods were labour-intensive. One of the first known procedures, published in 1869, recommended that leeches be used to collect blood from the patient. A microbiology textbook from 1911 noted that decontamination of the draw site and equipment could take over an hour, and that due to a lack of effective methods for preserving blood, the cultures would sometimes have to be prepared at the patient's bedside. In addition to subculturing the broth, some protocols specified that the blood be mixed with melted agar and the mixture poured into a petri dish. In 1915, a blood culture collection system consisting of glass vacuum tubes containing glucose broth and an anticoagulant was described. Robert James Valentine Pulvertaft published a seminal work on blood cultures in 1930, specifying—among other insights—an optimal blood-to-broth ratio of 1:5, which is still accepted today. The use of SPS as an anticoagulant and preservative was introduced in the 1930s and 40s and resolved some of the logistical issues with earlier methods. From the 1940s through the 1980s, a great deal of research was carried out on broth formulations and additives, with the goal of creating a growth medium that could accommodate all common bloodstream pathogens. In 1947, M.R. Castañeda invented a "biphasic" culture bottle for the identification of Brucella species, which contained both broth and an agar slant, allowing the agar to be easily subcultured from the broth; this was a precursor of some contemporary systems for manual blood cultures. E.G.
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.
Primary drying removes ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, often under the same vacuum. The two stages differ in the water state being removed.