This is a working overview of Sublimation, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-09. 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.
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 |
|---|---|---|
| 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. |
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.
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.
Lyophilization, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
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.
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.
By the possession of an intra-main-chain hydrogen bond between the CO of residue i and the NH of residue i+3; By having a distance of less than 7Å between the Cα atoms of residues i and i+3. The hydrogen bond criterion is the one most appropriate for everyday use, partly because it gives rise to four distinct categories; the distance criterion gives rise to the same four categories but yields additional turn types.
The Br–Br distance is 227 pm (close to the gaseous Br–Br distance of 228 pm) and the Br···Br distance between molecules is 331 pm within a layer and 399 pm between layers (compare the van der Waals radius of bromine, 195 pm). This structure means that bromine is a very poor conductor of electricity, with a conductivity of around 5 × 10−13 Ω−1 cm−1 just below the melting point, although this is higher than the essentially undetectable conductivity of chlorine. At a pressure of 55 GPa (roughly 540,000 times atmospheric pressure) bromine undergoes an insulator-to-metal transition. At 75 GPa it changes to a face-centered orthorhombic structure. At 100 GPa it changes to a body centered orthorhombic monatomic form.
=== Pharmacokinetics === Piperacillin is generally available in their stable form as crystallized potassium or sodium salt, quickly losing bactericidal activity upon dissolution due to their short half-lives. As the gastrointestinal tract does not absorb piperacillin and tazobactam, they are dissolved in a solution before being administered to a patient, through parenteral means. Excreted through renal mechanisms like glomerular or tubular filtration as a component of urine, uncontrolled dosages of the drug can cause renal dysfunction and competitive inhibition of excretion, delaying piperacillin-tazobactam excretion, and endangering patients to drug exposure.
The making and drinking of cider is traditional in several areas of northern Spain, mainly Galicia, the Principality of Asturias, Cantabria, and the Basque Country. The largest producer of cider in Spain is the Atlantic region of Asturias, where cider is considered not only a beverage but an intrinsic part of its culture and folklore. Asturias amounts more than 80% of the whole production of Spain. The consumption of cider in Asturias is of 54 litres per person/year, probably the highest in any European region. The first testimony about cider in Asturias was made by Greek geographer Strabo in 60 BC. The traditional Asturian sidra is a still cider of 4–8% strength, although there are other varieties. Traditionally, it is served in sidrerías and chigres, pubs specialising in cider where it is also possible to have other drinks as well as traditional food. One of the most outstanding characteristics is that it is poured in very small quantities from a height into a wide glass, with the arm holding the bottle extended upwards and the one holding the glass extended downward. This technique is called escanciar un culín (also echar un culín) and is done to get air bubbles into the drink (espalmar), thus giving it a sparkling taste like Champagne that lasts a very short time. Cider is also poured from barrels in the traditional Espichas. One of the most popular ciders in Spain is called "El Gaitero" (the bagpipe player) which can be found everywhere in Spain and which is produced in this region.
Sources: en.wikipedia.org
== Biosynthesis == Oxaloacetate forms in several ways in nature. A principal route is upon oxidation of L-malate, catalyzed by malate dehydrogenase, in the citric acid cycle. Malate is also oxidized by succinate dehydrogenase in a slow reaction with the initial product being enol-oxaloacetate. It also arises from the condensation of pyruvate with carbonic acid, driven by the hydrolysis of ATP:
1.3 L (1,323 cc) B3-ME, I4 16-valve SOHC, FI, 73–84 PS (54–62 kW; 72–83 hp) / 104–110 N⋅m (77–81 lb⋅ft) (1994–2000) 1.5 L (1,489 cc) Z5-DE, I4 16-valve DOHC, FI, 88–110 PS (65–81 kW; 87–108 hp) / 130–137 N⋅m (96–101 lb⋅ft) (1994–2000) 1.5 L (1,489 cc) Z5-DEL, I4 16-valve DOHC, FI, lean burn, 94 PS (69 kW; 93 hp) / 132 N⋅m (97 lb⋅ft) (1996–1998) 1.5 L (1,498 cc) B5-ZE, I4 16-valve DOHC, FI, 125 PS (92 kW; 123 hp) / 129 N⋅m (95 lb⋅ft) (1994–1996) 1.6 L (1,597 cc) B6D, I4 16-valve DOHC, FI, 115 PS (85 kW; 113 hp) / 140 N⋅m (103 lb⋅ft) (1996–1998) 1.8 L (1,839 cc) BP-ZE, I4 16-valve DOHC, FI, 114–140 PS (84–103 kW; 112–138 hp) / 157–163 N⋅m (116–120 lb⋅ft) (1995–2000) Diesel:
Hyperproinsulinemia is a disease where insulin is not sufficiently processed before secretion and immature forms of insulin make up the majority of circulating insulin immunoreactivity in both fasting and glucose-stimulated conditions (insulin immunoreactivity refers to all molecules detectable by an insulin antibody, i.e. insulin, proinsulin, and proinsulin-like material). The term is composed of hyper - high, proinsulin - immature insulin molecule, and -emia - blood condition. Hyperproinsulinemia is more frequent in type 2 diabetes. It has been attributed to either a direct β-cells defect or an indirect effect of cell dysregulation under sustained elevated blood glucose (hyperglycemia). Some alleles of insulin can cause hyperproinsulinemia (see table 2: monogenic forms of type 1 diabetes, INS (insulin). For a more detailed descriptions of the insulin gene variations leading to hyperproinsulinemia see NCBI's OMIM 176730
= Reaction volume The SI unit is the katal, 1 katal = 1 mol s−1 (mole per second), but this is an excessively large unit. A more practical and commonly used value is enzyme unit (U) = 1 μmol min−1 (micromole per minute). 1 U corresponds to 16.67 nanokatals. Enzyme activity as given in katal generally refers to that of the assumed natural target substrate of the enzyme. Enzyme activity can also be given as that of certain standardized substrates, such as gelatin, then measured in gelatin digesting units (GDU), or milk proteins, then measured in milk clotting units (MCU). The units GDU and MCU are based on how fast one gram of the enzyme will digest gelatin or milk proteins, respectively. 1 GDU approximately equals 1.5 MCU. An increased amount of substrate will increase the rate of reaction with enzymes, however once past a certain point, the rate of reaction will level out because the amount of active sites available has stayed constant.
=== Testing === The American Heart Association recommends testing cholesterol every four to six years for people aged 20 years or older. A separate set of American Heart Association guidelines issued in 2013 indicates that people taking statin medications should have their cholesterol tested 4–12 weeks after their first dose and then every 3–12 months thereafter. For men ages 45 to 65 and women ages 55 to 65, a cholesterol test should be performed every one to two years, and an annual test should be performed for seniors over the age of 65. After 12 hours of fasting, a blood sample is taken by a healthcare professional from an arm vein to measure a lipid profile for a) total cholesterol, b) HDL cholesterol, c) LDL cholesterol, and d) triglycerides. Results may be expressed as "calculated", indicating a calculation of total cholesterol, HDL, and triglycerides. Cholesterol is tested to determine for "normal" or "desirable" levels if a person has a total cholesterol of 5.2 mmol/L or less (200 mg/dL), an HDL value of more than 1 mmol/L (40 mg/dL, "the higher, the better"), an LDL value of less than 2.6 mmol/L (100 mg/dL), and a triglycerides level of less than 1.7 mmol/L (150 mg/dL). Blood cholesterol in people with lifestyle, aging, or cardiovascular risk factors, such as diabetes mellitus, hypertension, family history of coronary artery disease, or angina, are evaluated at different levels.
Sources: en.wikipedia.org
The intent was to identify donors potentially infected with hepatitis C because no specific test for that disease was available at the time. Prior to July 1992, widespread blood donation testing in the US for hepatitis C was not carried out by major blood banks. With the introduction of second-generation ELISA antibody tests for hepatitis C, the Red Cross changed the ALT policy. As of July 2003, donors previously disqualified for elevated ALT levels and no other reason may be reinstated as donors when they contact the donor-counseling department of their regional Red Cross organization. In 2000, the American Association for Clinical Chemistry determined that the appropriate terminology for AST and ALT are aspartate aminotransferase and alanine aminotransferase. The term transaminase is outdated and no longer used in liver disease.
== Poiseuille flow in a pipe with an oscillating pressure gradient == Flow through pipes with an oscillating pressure gradient finds applications in blood flow through large arteries. The imposed pressure gradient is given by
Bennie and colleagues proposed a method for chemical euthanasia of insects and other terrestrial arthropods. As of 2024, the Insect Welfare Research Society guidelines for protecting and promoting insect welfare in research recommend chemical agents, rapid freezing, immersion in alcohol following anesthesia, or crushing/grinding as methods that may humanely euthanize insects. Insect welfare is currently not regulated in research settings, resulting in the frequent reporting of some low-welfare practices such as vivisection (live dissection of an animal without anesthetics) in the discipline. Recent research suggests that the Canadian public believes insect welfare in research should be regulated to 2/3rds the level of oversight given to vertebrates. Some authors, including animal ethicists and academics that research insect farming, have begun extending discussions of insect welfare beyond the laboratory to the domain of raising insects for food, feed, or pet food. The Dutch Animal Act, which went into effect on 1 January 2013, created a regulatory framework for farm-animal welfare based on the Five Freedoms, and the law specifically lists a number of insect species as "production animals" whose wellbeing needs to be respected. Dutch politician Marianne Thieme asked a series of questions suggesting concern that insect farming would multiply the number of animals farmed and killed for human consumption.
== Gene == The IGFBP3 gene (or IBP3), on human chromosome 7, is organized into four protein-coding exons with a 5th exon in the 3' untranslated region. It is located adjacent to the IGFBP1 gene in tail-to-tail orientation, separated by 20 kb.
== Background == Found in several fungal species such as Fusarium graminearum NRRL 2903 (formerly misidentified as Dactylium dendroides), and other species of Fusarium and Aspergillus genera, galactose oxidase was first isolated in 1959. This enzyme is secreted by fungi to function in extracellular space. Although the oxidation reaction of D-galactose gives galactose oxidase its name, the coupled reduction of dioxygen to hydrogen peroxide is believed to have greater physiological significance in yeasts. Hydrogen peroxide which can be produced by yeasts in this way is possibly a bacteriostatic agent.
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.
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.