The short version of Collapse temperature fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-07-02. Anything still debated is marked as such rather than presented as settled.
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.
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 name | Freeze-drying | Process removes water by sublimation under vacuum. |
| Typical primary drying shelf temperature | -40 C to -10 C | Set below the formulation's collapse temperature. |
| Typical chamber pressure | 0.05-0.3 mbar | Low pressure allows ice to sublime below its triple point. |
| Water content after drying | 0.5-3% by weight | Higher values may reduce storage stability for some materials. |
| Key thermal parameter | Collapse temperature | Measured by freeze-drying microscopy or differential scanning calorimetry. |
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
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.
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.
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.
=== Original format === The original FASTA/Pearson format is described in the documentation for the FASTA suite of programs. It can be downloaded with any free distribution of FASTA (see fasta20.doc, fastaVN.doc, or fastaVN.me—where VN is the Version Number). In the original format, a sequence was represented as a series of lines, each of which was no longer than 120 characters and usually did not exceed 80 characters. This probably was to allow for the preallocation of fixed line sizes in software: at the time most users relied on Digital Equipment Corporation (DEC) VT220 (or compatible) terminals which could display 80 or 132 characters per line. Most people preferred the bigger font in 80-character modes and so it became the recommended fashion to use 80 characters or less (often 70) in FASTA lines. Also, the width of a standard printed page is 70 to 80 characters (depending on the font). Hence, 80 characters became the norm. The first line in a FASTA file started either with a ">" (greater-than) symbol or, less frequently, a ";" (semicolon) was taken as a comment. Subsequent lines starting with a semicolon would be ignored by software. Since the only comment used was the first, it quickly became used to hold a summary description of the sequence, often starting with a unique library accession number, and with time it has become commonplace to always use ">" for the first line and to not use ";" comments (which would otherwise be ignored).
=== Incidents === The 1981 Louisville sewer explosions, which destroyed over 13 mi (21 km) of sewer lines and streets in the Kentucky city, were caused by ignition of hexane vapors which had been illegally discharged from a soybean processing plant owned by Ralston-Purina. Hexane was attributed as the cause of an explosion that occurred in the National University of Río Cuarto, Argentina on 5 December 2007, due to a hexane spill near a heat-producing machine that exploded, producing a fire that killed one student and injured 24 more. Occupational hexane poisoning has occurred with Japanese sandal workers, Italian shoe workers, Taiwan press proofing workers, and others. Analysis of Taiwanese workers has shown occupational exposure to substances including n-hexane. In 2010–2011, Chinese workers manufacturing iPhones were reported to have suffered hexane poisoning.
=== Charles and Francis Darwin (1880) === Although known primarily for his work on the Theory of Evolution, Charles Darwin was also keenly interested in plants. Through the 1870s, he and his son Francis studied the movement of plants towards light. They were able to show that light is perceived at the tip of a young stem (the coleoptile), whereas the bending occurs lower down the stem. They proposed that a 'transmissible substance' communicated the direction of light from the tip down to the stem. The idea of a 'transmissible substance' was initially dismissed by other plant biologists, but their work later led to the discovery of the first plant hormone. In the 1920s Dutch scientist Frits Warmolt Went and Russian scientist Nikolai Cholodny (working independently of each other) conclusively showed that asymmetric accumulation of a growth hormone was responsible for this bending. In 1933 this hormone was finally isolated by Kögl, Haagen-Smit and Erxleben and given the name 'auxin'.
Carl Gustav Jung ( YUUNG; Swiss Standard German: [ˈkarl ˈjʊŋ]; 26 July 1875 – 6 June 1961) was a Swiss psychiatrist, psychotherapist, and psychologist who founded the school of analytical psychology. He was a prolific author of over twenty books, illustrator, correspondent, and academic, best known for his concept of archetypes. Widely considered one of the most influential psychologists of all time, Jung's work has fostered not only scholarship, but also popular interest. His work has been influential in the fields of psychiatry, anthropology, archaeology, literature, philosophy, psychology, and religious studies. Jung worked as a research scientist at the Burghölzli psychiatric hospital in Zurich, under Eugen Bleuler. He established himself as an influential mind, developing a friendship with Sigmund Freud, the founder of psychoanalysis, and conducting a lengthy correspondence regarding their joint vision of human psychology. Freud saw the younger Jung not only as the heir he had been seeking to take forward his "new science" of psychoanalysis, but as a means to legitimise his own work: Freud and other contemporary psychoanalysts were Jews facing rising antisemitism in Europe, while Jung was raised as Christian, although he did not strictly adhere to traditional Christian doctrine, seeing religion, including Christianity, as a powerful expression of the human psyche and its search for meaning. Freud secured Jung's appointment as president of Freud's newly founded International Psychoanalytical Association.
The foundation charged the new project with development, testing, licensure and mass introduction of a meningococcal conjugate vaccine. In 2002, the collaboration supported reinforced meningitis surveillance activities in 12 countries in Africa: Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Ethiopia, Ghana, Ivory Coast, Mali, Niger, Nigeria and Togo. The surveillance indicated an increased risk of outbreaks in the future and the continued need for a vaccine. MenAfriVac became available for widespread use in African meningitis belt countries in 2010. Distribution in Mali and Niger was assisted by Médecins Sans Frontières.
Sources: en.wikipedia.org
Sutherland goes further to say that deviancy is contingent on conflicting groups within society, and that such groups struggle over the means to define what is criminal or deviant within society. Criminal organizations therefore gravitate around illegal avenues of production, profit-making, protectionism or social control and attempt (by increasing their operations or membership) to make these acceptable. This also explains the propensity of criminal organizations to develop protection rackets, to coerce through the use of violence, aggression and threatening behavior (at times termed 'terrorism'). Preoccupation with methods of accumulating profit highlight the lack of legitimate means to achieve economic or social advantage, as does the organization of white-collar crime or political corruption (though it is debatable whether these are based on wealth, power or both). The ability to effect social norms and practices through political and economic influence (and the enforcement or normalization of criminogenic needs) may be defined by differential association theory.
For example, it has been shown that IPF patients who have a specific genotype in the mucin MUC5B gene polymorphism (see above) experience slower decline in FVC and significantly improved survival. Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on specific genotypes is still not possible.
=== Identification of a suitable chain === Consult the saw's manual to determine which chain/bar combinations are compatible with the saw. A given saw will usually accept a number of different bars and chains.
==== Colleges and universities ==== Due to low standards and requirements in high school, many Americans are entering institutions of higher learning, including elite schools, with deficient reading comprehension skills and are unable and unwilling to complete long reading assignments. In addition, about a quarter of American university students failed to graduate within six years in the late 2010s and those who did faced diminishing wage premiums. As Generation Z enters high school and preparing for college, a primary concern is paying for a higher education without acquiring debt. As of 2019, the total college debt has exceeded $1.5 trillion, and two out of three college graduates are saddled with debt. In response to these challenges, many schools have diversified their sources of revenue in order to offer their students greater tuition discounts. Students also report interest in Reserve Officers' Training Corps (ROTC) programs as a means of covering college costs. Indeed, college subsidies are one of the most attractive things about signing up for military service. Another enticement is signing bonuses, whose amounts vary according to specialty. Domestic undergraduate enrollment since the early 2010s. Due to population aging, the number of college-aged people in the United States will fall after 2025, making it easier for people born in the late 2000s and after to get admitted.
Sources: en.wikipedia.org
The first use of the term in this sense, to describe the post–World War II geopolitical tensions between the USSR and its satellites and the United States and its western European allies, is attributed to Bernard Baruch, an American financier and presidential advisor. In South Carolina, on April 16, 1947, he delivered a speech (by journalist Herbert Bayard Swope) saying, "Let us not be deceived: we are today in the midst of a cold war." Newspaper reporter-columnist Walter Lippmann gave the term wide currency, with the book Cold War (1947). The term "hot war" is also occasionally used by contrast, but remains rare in literature on military theory. According to academic Covell Meyskens, the term "cold war" was not employed in China during the Maoist era.
Due to declining interest in higher education and a tight labor market, in the early 2020s, young Americans could expect to be hired right after graduating high school. In May 2023, the unemployment rate of Americans aged 16 to 24 was 7.5%, the lowest in 70 years. Among teenagers 16 to 19, employment numbers have gone up, though not to the level seen among the Baby Boomers and Generation X when they were teenagers due to a variety of factors, including jobs being automated, outsourced, or given to immigrants, and state governments regulating the job market more tightly. Yet despite a relatively strong labor market and falling inflation, young Americans tend to be pessimistic about their economic prospects, worrying about a possible recession, expensive housing, and the possibility of being laid off. Anxious about student debt, industrial automation, and artificial intelligence, Generation Z is increasingly interested in skilled trades, which they and their parents view as quicker and more affordable paths towards prosperity. Generation Z is more concerned about mass unemployment due to artificial intelligence (AI) rather than outsourcing or immigration. Indeed, many entry-level white-collar positions have been eliminated by AI, and since the late 2010s, the United States faces a shortage of blue-collar workers. Whenever they find themselves short on skills, Generation Z will pick up what they need using the Internet. Millennials and Generation Z are overwhelmingly more likely than Baby Boomers to think that it is the job of employees to train themselves.
==== Inflammation and allergy ==== 12-HHT stimulates chemotactic responses in mouse bone marrow mast cells, which naturally express BLT2 receptors, as well as in Chinese hamster ovary cells made to express these receptors by transfection. These findings suggest that the 12-HHT/BLT2 receptor pathway may support the pro-inflammatory (i.e. chemotactic) actions of the LTB4/BLT1 pathway. On the other hand, the immortalized human skin cell line HaCaT expresses BLT2 receptors and responds to ultraviolet B (UVB) radiation by generating toxic reactive oxygen species which in turn cause the HaCaT cells to die by activating apoptotic pathways in a BLT2 receptor-dependent reaction. Topical treatment of mouse skin with a BLT2 receptor antagonist, LY255283, protects against UVB radiation-induced apoptosis and BLT2-overexpressing transgenic mice exhibited significantly more extensive skin apoptosis in response to UVB irradiation. Furthermore, 12-HHT inhibits HaCaT cells from synthesizing interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation, in response to UVB radiation. These results suggest that the 12-HHT/BLT2 axis can act to suppress inflammation by promoting the orderly death of damaged cells and blocking IL-6 production. Opposition between the pro-inflammatory LTB4/BLT1 and anti-inflammatory actions of the 12-HHT/BLT2 axes occurs in another setting.
Small molecule targets Protein targets Cells and tissues Multiple rounds of selection and counter-selection are performed as part of each Optimer discovery process. Each discovery process can be adapted to include specific target, assay and buffer conditions to improve Optimer selection.
=== Jet milling === Jet milling (also called fluid energy milling) is the most widely used industrial technique for micronizing active pharmaceutical ingredients and similar fine chemicals. Unlike ball or media mills, jet mills contain no moving grinding bodies; particle size reduction is achieved by high-velocity particle–particle collisions in a stream of compressed gas, typically nitrogen or dry air. In a fluid energy (jet) mill, particles are entrained in one or more high-velocity gas streams and size reduction occurs primarily through collisions between the particles themselves rather than impact with the mill walls, which minimises contamination; the cooling produced by expansion of the compressed gas also permits the milling of heat-sensitive materials. Spiral jet mills, which have no moving parts, are widely used to micronize pharmaceutical substances to narrow size distributions in the low-micrometre range. The most common configuration is the spiral jet mill (also called a pancake or loop mill), in which feed material is introduced into a flat cylindrical chamber through a Venturi and accelerated by tangential gas jets. Coarse particles are retained near the chamber wall by centrifugal force and continue to be ground, while fines exit through a central classifier outlet. Spiral jet mills routinely achieve volume median diameters (D50) of 1–10 μm without product contact with mechanical grinding surfaces, making the technology attractive for high-purity and abrasion-sensitive materials.
Sources: en.wikipedia.org
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.
Freezing determines ice crystal size, pore structure, and the concentration of solutes in remaining liquid. Faster freezing generally creates smaller ice crystals and a denser dried matrix. These features affect drying rate and reconstitution behavior.
Lyophilization reduces water content but usually leaves a small amount of water in the dried material. Some water remains bound to solids or trapped in the dried matrix. Very low water targets can require extended secondary drying, which may alter product 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.