The short version of sublimation fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2025-11-12. Anything still debated is marked as such rather than presented as settled.
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.
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.
Stability programs monitor lyophilized products under defined temperature and humidity conditions over time. Real-time studies at recommended storage conditions are the reference, while accelerated studies provide early signals of degradation pathways. Because a dry cake can still undergo oxidation, hydrolysis, or aggregation, stability depends on residual moisture, excipients, and container headspace. Open questions include how best to predict long-term stability from short accelerated runs and how vial-to-vial variability affects shelf life. Current guidance treats these predictions as product-specific rather than universally generalizable.
Freeze-dried materials are hygroscopic to varying degrees and can take up moisture after drying. Storage therefore often uses sealed glass vials, rubber stoppers, and crimp seals to limit contact with ambient humidity. A desiccant may be included for moisture-sensitive products, although it is not universal. Controlled room temperature is sufficient for many lyophilizates, while others require refrigeration or freezing. Moisture ingress remains a primary cause of cake collapse, chemical degradation, and loss of reconstitution performance.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilization is the American spelling; lyophilisation is British |
| Primary drying mechanism | Sublimation of ice | Occurs under vacuum below the triple point |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product and equipment |
| Typical shelf temperature during freezing | -40 to -20 °C | Lower temperatures may be used for labile products |
| Resulting product form | Porous cake or powder | Appearance depends on formulation and cycle |
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
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.
After drying, a lyophilized product is usually sealed under vacuum or an inert gas to limit moisture uptake. Residual water content is measured because small changes can alter chemical stability and cake appearance. Storage temperature depends on the material; many biological products are kept at 2–8 °C, while some require −20 °C or colder. Exposure to ambient humidity during handling can cause the porous solid to absorb water and collapse. Container closures and stoppers are therefore selected for low moisture transmission and compatibility.
Quality control for lyophilized materials includes visual inspection of the cake, measurement of residual moisture, and tests for reconstitution time. An acceptable cake is typically uniform and may be slightly porous; shrinkage, meltback, or cracks can indicate process deviations. Analytical methods such as Karl Fischer titration, thermogravimetric analysis, and near-infrared spectroscopy quantify water content. Reconstitution time is recorded because a very slow or incomplete dissolution can signal collapse or aggregation. Stability studies compare samples stored under defined temperature and humidity conditions over months or years.
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.
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.
Lyophilized products are typically stored as sealed solids in vials or syringes. Moisture ingress is a major concern because many dried cakes are hygroscopic and can lose stability when exposed to humid air. Storage temperature depends on the formulation; some products are kept refrigerated, while others are stable at room temperature. Container closure integrity and headspace moisture are often monitored. Light protection may also be required for some photosensitive materials.
Quality control for lyophilized materials includes visual inspection, residual moisture measurement, and reconstitution testing. Cake appearance can reveal process problems such as collapse, shrinkage, or meltback, although appearance alone does not prove potency. Residual moisture is commonly measured by Karl Fischer titration or by loss on drying. Reconstitution time is checked because a slow or incomplete dissolve can indicate a change in pore structure. Stability studies track these attributes over time under defined temperature and humidity conditions.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
== See also == List of University of California, Berkeley faculty List of University of California, Berkeley alumni in business and entrepreneurship List of University of California, Berkeley alumni in science and technology
For reasons of space, the periodic table is commonly presented with the f-block elements cut out and positioned as a distinct part below the main body. This reduces the number of element columns from 32 to 18. Both forms represent the same periodic table. The form with the f-block included in the main body is sometimes called the 32-column or long form; the form with the f-block cut out the 18-column or medium-long form. The 32-column form has the advantage of showing all elements in their correct sequence, but it has the disadvantage of requiring more space. The form chosen is an editorial choice, and does not imply any change of scientific claim or statement. For example, when discussing the composition of group 3, the options can be shown equally (unprejudiced) in both forms. Periodic tables usually at least show the elements' symbols; many also provide supplementary information about the elements, either via colour-coding or as data in the cells. Tables may include extra information such as the names and atomic numbers of the elements, their blocks, natural occurrences, standard atomic weight, states of matter, melting and boiling points, densities, as well as provide different classifications of the elements.
== Lifestyle protective factors == Exercise and caffeine consumption are known to help decrease the risks of PD. Diet can also affect the level of risk: eating patterns rich in fruits, vegetables, whole grains, and fish, are associated with reduced risk of Parkinson's disease, while diets high in red meats and processed foods are associated with increased risk.
Cocaine is a highly-trafficked prohibited drug. The value of the global market for illicit cocaine was estimated at between $94 and $143 billion in 2017. In 2022, illicit sales in Europe were estimated at $11.1 billion. In 2020, almost 2,000 tons of cocaine were produced for distribution through illicit markets.
=== Uses of derivatives === In the laboratory, it is used to detect the presence of alkaline phosphatase activity by hydrolysis of pNPP. In basic conditions, presence of hydrolytic enzymes will turn reaction vessel yellow. 4-Nitrophenol is a product of the enzymatic cleavage of several synthetic substrates such as 4-nitrophenyl phosphate (used as a substrate for alkaline phosphatase), 4-nitrophenyl acetate (for carbonic anhydrase), 4-nitrophenyl-β-D-glucopyranoside and other sugar derivatives which are used to assay various glycosidase enzymes. Amounts of 4-nitrophenol produced by a particular enzyme in the presence of its corresponding substrate can be measured with a spectrophotometer at or around 405 nm and used as a proxy measurement for the amount of the enzyme activity in the sample. Accurate measurement of enzyme activity requires that the 4-nitrophenol product is fully deprotonated, existing as 4-nitrophenolate, given the weak absorbance of 4-nitrophenol at 405 nm. Complete ionization of the alcohol functional group affects the conjugation of the pi bonds on the compound. A lone pair from the oxygen can be delocalized via conjugation to the benzene ring and nitro group. Since the length of conjugated systems affects the color of organic compounds, this ionization change causes the 4-nitrophenol to turn yellow when fully deprotonated and existing as 4-nitrophenolate. A common mistake in measuring enzyme activity using these substrates is to perform the assays at neutral or acidic pH without considering that only part of the chromophoric product is ionized.
Sources: en.wikipedia.org
=== Overdose === Overdosage may result in vomiting, sedation, disturbances in heart rhythm, dizziness, sweating, nausea, tremors, and rarely amnesia, confusion, coma, or convulsions. Overdose deaths have occurred, sometimes involving other drugs, but also with citalopram as the sole agent. Citalopram and N-desmethylcitalopram may be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Blood or plasma citalopram concentrations are usually in a range of 50-400 μg/L in persons receiving the drug therapeutically, 1000–3000 μg/L in patients who survive acute overdosage, and 3–30 mg/L in those who do not survive. It is the most dangerous of SSRIs in overdose.
In 2005, 51 million Brazilian nationals made ten times more trips than foreign tourists and spent five times more money than their international counterparts. The main destination states in 2023 were São Paulo, Rio de Janeiro, and Rio Grande do Sul. The main source of tourists for the entire country is São Paulo state. In terms of tourism revenues, the top earners by state were São Paulo and Bahia. For 2005, the three main trip purposes were visiting friends and family (53.1%), sun and beach (40.8%), and cultural tourism (12.5%).
=== Physical activity === Physical inactivity of children has also shown to be a serious cause, and children who fail to engage in regular physical activity are at greater risk of obesity. Researchers studied the physical activity of 133 children over a three-week period using an accelerometer to measure each child's level of physical activity. They discovered the obese children were 35% less active on school days and 65% less active on weekends compared to non-obese children. Physical inactivity as a child could result in physical inactivity as an adult. In a fitness survey of 6,000 adults, researchers discovered that 25% of those who were considered active at ages 14 to 19 were also active adults, compared to 2% of those who were inactive at ages 14 to 19, who were now said to be active adults. Staying physically inactive leaves unused energy in the body, most of which is stored as fat. Researchers studied 16 men over a 14-day period and fed them 50% more of their energy required every day through fats and carbohydrates. They discovered that carbohydrate overfeeding produced 75–85% excess energy being stored as body fat and fat overfeeding produced 90–95% storage of excess energy as body fat. Many children fail to exercise because they spend long periods of time engaging in sedentary activities such as computer usage, playing video games or watching television. Technology usage may lead to reduced physical activity and is a risk factor for obesity; recreational screen time of 2 hours or more per day is associated with an increased risk of obesity.
A trivalent element, pure erbium metal is malleable (or easily shaped), soft yet stable in air, and does not oxidize as quickly as some other rare-earth metals. Its salts are rose-colored, and the element has characteristic sharp absorption spectra bands in visible light, ultraviolet, and near infrared. Otherwise it looks much like the other rare earths. Its sesquioxide is called erbia. Erbium's properties are to a degree dictated by the kind and amount of impurities present. Erbium does not play any known biological role, but is thought to be able to stimulate metabolism. Erbium is ferromagnetic below 19 K, antiferromagnetic between 19 and 80 K and paramagnetic above 80 K. Erbium can form propeller-shaped atomic clusters Er3N, where the distance between the erbium atoms is 0.35 nm. Those clusters can be isolated by encapsulating them into fullerene molecules, as confirmed by transmission electron microscopy. Like most rare-earth elements, erbium is usually found in the +3 oxidation state. However, it is possible for erbium to also be found in the 0, +1 and +2 oxidation states.
Sources: en.wikipedia.org
Transmitter uptake and release: Astrocytes express plasma membrane transporters for several neurotransmitters, including glutamate, ATP, and GABA. More recently, astrocytes were shown to release glutamate or ATP in a vesicular, Ca2+-dependent manner. (This has been disputed for hippocampal astrocytes.) Regulation of ion concentration in the extracellular space: Astrocytes express potassium channels at a high density. When neurons are active, they release potassium, increasing the local extracellular concentration. Because astrocytes are highly permeable to potassium, they rapidly clear the excess accumulation in the extracellular space. If this function is interfered with, the extracellular concentration of potassium will rise, leading to neuronal depolarization by the Goldman equation. Abnormal accumulation of extracellular potassium is well known to result in epileptic neuronal activity. Trace metal homeostasis: Astrocytes are the principal regulators of trace metal homeostasis in the central nervous system. They serve as the main storage and distribution sites for copper, manganese, zinc and iron, protecting neurons from metal-induced toxicity while supplying these essential cofactors. Astrocytes accumulate copper efficiently via the high-affinity transporter CTR1 and store it bound to glutathione and metallothioneins. They export copper via the copper-transporting ATPase ATP7A, thereby supplying copper to neighbouring neurons. Astrocytes are the main storage site for manganese in the brain, accumulating roughly 50 times more Mn²⁺ than neurons.
In 1928 he obtained a Rockefeller Travelling Fellowship to visit Europe, where he worked for a while in the Anatomical School at Cambridge University, England, then headed by Professor Wilson, and in the Anatomical School at Utrecht University, the Netherlands, then headed by Professor Boecke. Also in 1928, Oscar Tiegs was awarded the David Syme Research Prize. As a histologist Oscar Tiegs developed an interest in Boecke's suggestion of a double innervation of vertebrate skeletal muscle. From this interest he undertook a physiological investigation of the sympathetic system in the muscle, finding no such action except in blood vessels, all muscular action seemingly being caused by an adrenaline-like substance. Oscar Tiegs in this work corrected errors and ambiguities in the work of others, and showed the validity of some traditional interpretations.
Noriega married Felicidad Sieiro in the late 1960s, and the couple had three daughters: Lorena; Sandra; and Thays. Sieiro had been a school teacher, and Noriega a member of the National Guard. Her family, of Basque heritage, was reported to have been unhappy with the marriage. Noriega was repeatedly unfaithful to his wife, who at one point expressed a desire for a divorce, though she changed her mind later.
Sources: en.wikipedia.org
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.
Vacuum lowers the pressure below the triple point of water, allowing ice to sublimate directly into vapor. It also helps remove water vapor from the product chamber and shortens primary drying.
Many aqueous solutions and suspensions can be freeze-dried, but some formulations collapse or do not form a stable cake. The process requires careful formulation and cycle development.
Many dried cakes are hygroscopic and can adsorb water during storage or handling. Absorbed moisture may lower the glass transition temperature and promote chemical reactions. Sealed packaging and controlled humidity reduce this risk.