A practical reference on Sublimation: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-07-01. 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.
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.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback 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.
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.
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 couples heat transfer, mass transfer, and phase behavior. Sublimation requires a vapor pressure difference between the ice front and the chamber, and the dried layer adds resistance to vapor flow. Amorphous formulations are characterized by a glass transition temperature of the maximally freeze-concentrated solute, often denoted Tg'. Crystalline bulking agents can provide structure, while amorphous excipients stabilize labile components. Open questions remain about spatial heterogeneity, edge effects, and how laboratory cycles scale to production.
Lyophilization is a drying process in which a solvent, usually water, is removed from a frozen material by sublimation under reduced pressure. The material is first solidified, then placed under vacuum so that ice transitions directly to vapor without a bulk liquid phase. This approach suits heat-sensitive substances that would degrade during conventional evaporation. Primary drying removes unbound ice, while secondary drying reduces water that remains adsorbed to the solid matrix. The result is a porous, lightweight solid that can be reconstituted later.
duplication The production of a second copy of part or all of a nucleotide sequence or amino acid sequence, either naturally or artificially, and the retention of both copies; especially when both the copy and the original sequence are retained in situ within the same molecule, often but not necessarily adjacent to each other. See also gene duplication, chromosomal duplication, and repeat.
=== Early years === Sidney Fox was the son of Jacob Fox, a wig-maker, and Louise Berman, a Ukrainian immigrant. Fox married Raia Joffe Fox and they had three sons: Lawrence, Ronald, and Thomas. All three of his sons became scientists. His family was Jewish. Fox obtained a Bachelor of Arts degree from University of California, Los Angeles in Chemistry. He went on to earn a Ph.D. from California Institute of Technology in 1940 and did his postdoctoral work at the Linus Pauling Laboratory where he grew close with Linus Pauling.
Unlike atomic absorption spectroscopy, which can only measure a single element at a time, ICP-MS has the capability to scan for all elements simultaneously. This allows rapid sample processing. A simultaneous ICP-MS that can record the entire analytical spectrum from lithium to uranium in every analysis won the Silver Award at the 2010 Pittcon Editors' Awards. An ICP-MS may use multiple scan modes, each one striking a different balance between speed and precision. Using the magnet alone to scan is slow due to hysteresis but is precise. Electrostatic plates can be used in addition to the magnet to increase the speed, and with multiple collectors can allow a scan of every element from Lithium 6 to Uranium Oxide 256 in less than a quarter of a second. For low detection limits, interfering species and high precision, the counting time can increase substantially. The rapid scanning, large dynamic range and large mass range of ICP-MS is ideally suited to measuring multiple unknown concentrations and isotope ratios in samples that have had minimal preparation (an advantage over TIMS). The analysis of seawater, urine, and digested whole rock samples are examples of industry applications. These properties also lend well to laser-ablated rock samples, where the scanning rate is fast enough to enable a real-time plot of any number of isotopes. This also allows easy spatial mapping of mineral grains.
=== Washed red blood cells === Red blood cell concentrates still contain a small amount of plasma after standard processing (usually 10-15 mL). In order to reduce the risk of allergic reactions to plasma proteins, or to modify the red blood cell concentrates for patients who are sensitive to IgA or potassium ions (K+), the red blood cell concentrates can be washed. Washing typically consists of diluting the red blood cells in saline-based washing solution or red blood cell additive solutions and then washing away any remaining plasma and debris during one or several centrifugation cycles. The process can be performed manually, or with an automated cell washer or processor.
==== Insulin resistance ==== Obesity has been contributing to increased insulin resistance in the global population. Insulin resistance increases hyperglycemia because the body becomes oversaturated by glucose. Insulin resistance desensitizes insulin receptors, preventing insulin from lowering blood sugar levels. The leading cause of hyperglycemia in type 2 diabetes is the failure of insulin to suppress glucose production by glycogenolysis and gluconeogenesis due to insulin resistance. Insulin normally inhibits glycogenolysis, but fails to do so in a condition of insulin resistance, resulting in increased glucose production. In the liver, FOXO6 normally promotes gluconeogenesis in the fasted state, but insulin blocks FOXO6 upon feeding. In a condition of insulin resistance, insulin fails to block FOXO6, resulting in continued gluconeogenesis even upon feeding.
Sources: en.wikipedia.org
=== Chronic exposures === The long-term toxicity of copper has not been well studied in humans, but it is infrequent in normal populations that do not have a hereditary defect in copper homeostasis. There is little evidence to indicate that chronic human exposure to copper results in systemic effects other than liver injury. Chronic copper poisoning leading to liver failure was reported in a young adult male with no known genetic susceptibility who consumed 30–60 mg/d of copper as a mineral supplement for 3 years. Individuals residing in U.S. households supplied with tap water containing >3 mg/L of copper exhibited no adverse health effects. No effects of copper supplementation on serum liver enzymes, biomarkers of oxidative stress, and other biochemical endpoints have been observed in healthy young human volunteers given daily doses of 6 to 10 mg/d of copper for up to 12 weeks. Infants aged 3–12 months who consumed water containing 2 mg Cu/L for 9 months did not differ from a concurrent control group in gastrointestinal tract (GIT) symptoms, growth rate, morbidity, serum liver enzyme and bilirubin levels, and other biochemical endpoints.) Serum ceruloplasmin was transiently elevated in the exposed infant group at 9 months and similar to controls at 12 months, suggesting homeostatic adaptation and/or maturation of the homeostatic response. Dermal exposure has not been associated with systemic toxicity but anecdotal reports of allergic responses may be a sensitization to nickel and cross-reaction with copper or a skin irritation from copper.
Popular protests broke out in early 2011, led by both secular and Islamist opposition groups. Longtime rebel groups like the Houthis and the Southern Movement also participated in the protests. Saleh responded with a violent crackdown, and the country nearly disintegrated into an all-out civil war as several army elements broke with the government and joined the protesters, beginning in March. Saleh was almost killed when a bomb went off in a mosque where he and other top government officials were praying on 3 June, apparently in an assassination attempt. While his condition initially appeared grave, Saleh recovered and returned to work on 23 September after several months of medical treatment in Saudi Arabia. He left Vice President Hadi in charge during his absence. As acting president, Hadi met with the opposition and reportedly expressed openness to political reforms. However, he rejected the idea of forcing Saleh from power without the president's consent.
In both males and females, FSH stimulates the maturation of primordial germ cells. In males, FSH induces Sertoli cells to secrete androgen-binding proteins (ABPs), regulated by inhibin's negative feedback mechanism on the anterior pituitary. Specifically, activation of Sertoli cells by FSH sustains spermatogenesis and stimulates inhibin B secretion. In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the concomitant rise in inhibin B, FSH levels then decline in the late follicular phase. This seems to be critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal phase, there is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle. Control of FSH release from the pituitary gland is unknown. Low frequency gonadotropin-releasing hormone (GnRH) pulses increase FSH mRNA levels in the rat, but is not directly correlated with an increase in circulating FSH. GnRH has been shown to play an important role in the secretion of FSH, with hypothalamic–pituitary disconnection leading to a cessation of FSH. GnRH administration leads to a return of FSH secretion. FSH is subject to oestrogen feed-back from the gonads via the hypothalamic pituitary gonadal axis.
In November 2024, the US Food and Drug Administration approved PropofolVet Multidose, the first generic propofol injectable emulsion for dogs. PropofolVet Multidose is approved for use as an injectable anesthetic in dogs. PropofolVet Multidose contains the same active ingredient (propofol injectable emulsion) as the approved brand-name drug product, PropoFlo 28, which was first approved on 4 February 2011. In addition, the FDA determined that PropofolVet Multidose contains no inactive ingredients that may significantly affect the bioavailability of the active ingredient.
Sources: en.wikipedia.org
=== Pharmacodynamics === Nemonapride has been described both as a typical antipsychotic and as an atypical antipsychotic. It is a potent and selective dopamine D2, D3, and D4 receptor antagonist. Its affinities (Ki) for these receptors are 0.16 nM for the dopamine D2 receptor, 0.26 nM for the dopamine D3 receptor, and 0.31 nM for the dopamine D4 receptor. Antagonism of the dopamine D2 receptor is thought to be responsible for the antipsychotic effects of nemonapride. In addition to the dopamine D2-like receptors, nemonapride has weaker affinity for the serotonin 5-HT1A and 5-HT2A receptors. Its affinities (Ki) for these receptors are 1.8 nM for the serotonin 5-HT1A receptor (11-fold lower than for the D2 receptor) and 9.4 nM for the serotonin 5-HT2A receptor (59-fold lower than for the D2 receptor). It is a partial agonist of the serotonin 5-HT1A receptor. It has very weak affinity for sigma receptors (Ki = 80–3,000 nM) as well. Besides these specific receptors, nemonapride is described as having very weak affinity for the dopamine D1, serotonin 5-HT2, adrenergic, and cholinergic receptors. In animals, nemonapride suppresses conditioned avoidance responses, inhibits methamphetamine- and apomorphine-induced hyperactivity and stereotypy, produces catalepsy, and has slight central depressant effects.
Strontium-90 is a radioactive fission product produced by nuclear reactors used in nuclear power. It is a major component of high-level radioactivity of nuclear waste and spent nuclear fuel. Its 29-year half-life is short enough that its decay heat has been used to power arctic lighthouses, but long enough that it can take hundreds of years to decay to safe levels. Exposure from contaminated water and food may increase the risk of leukemia, bone cancer and primary hyperparathyroidism.
This can be done to slides processed by the chemical fixation or frozen section slides. To see the tissue under a microscope, the sections are stained with one or more pigments. The aim of staining is to reveal cellular components; counterstains are used to provide contrast. The most commonly used stain in histology is a combination of hematoxylin and eosin (often abbreviated H&E). Hematoxylin is used to stain nuclei blue, while eosin stains the cytoplasm and the extracellular connective tissue matrix of most cells pink. There are hundreds of various other techniques which have been used to selectively stain cells. Other compounds used to color tissue sections include safranin, Oil Red O, congo red, silver salts and artificial dyes. Histochemistry refers to the science of using chemical reactions between laboratory chemicals and components within tissue. A commonly performed histochemical technique is the Perls' Prussian blue reaction, used to demonstrate iron deposits in diseases like Hemochromatosis. Recently, antibodies have been used to stain particular proteins, lipids and carbohydrates. Called immunohistochemistry, this technique has greatly increased the ability to specifically identify categories of cells under a microscope. Other advanced techniques include in situ hybridization to identify specific DNA or RNA molecules. These antibody staining methods often require the use of frozen section histology. These procedures above are also carried out in the laboratory under scrutiny and precision by a trained specialist medical laboratory scientist (a histoscientist).
=== Bulb blackening === In a conventional lamp, the evaporated tungsten condenses on the inner surface of the glass envelope, darkening it. For bulbs that contain a vacuum, the darkening is uniform across the entire surface of the envelope. When a filling of inert gas is used, the evaporated tungsten is carried in the thermal convection currents of the gas, and is deposited preferentially on the uppermost part of the envelope, blackening just that portion of the envelope. Study of the problem of bulb blackening led to the discovery of thermionic emission, the invention of the vacuum tube, and evaporation deposition used to make mirrors and other optical coatings. A very small amount of water vapor inside a light bulb can significantly increase lamp darkening. Water vapor dissociates into hydrogen and oxygen at the hot filament. The oxygen attacks the tungsten metal, and the resulting tungsten oxide particles travel to cooler parts of the lamp. Hydrogen from water vapor reduces the oxide, reforming water vapor and continuing this water cycle. The equivalent of a drop of water distributed over 500,000 lamps will significantly increase darkening. Small amounts of substances such as zirconium are placed within the lamp as a getter to react with any oxygen that may bake out of the lamp components during operation. Some old, high-powered lamps used in theater, projection, searchlight, and lighthouse service with heavy, sturdy filaments contained loose tungsten powder within the envelope.
== Related or interdisciplinary fields == Condensed matter physics, solid-state physics and solid-state chemistry Nanotechnology Mineralogy Supramolecular chemistry Biomaterials science Materials informatics
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 removes water by sublimation from a frozen material, while evaporation changes liquid water into vapor. The low-pressure freezing step avoids the liquid phase and can preserve heat-sensitive structures.