The short version of Collapse temperature fits in a sentence. The long version — which is the one that helps — is below.
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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.
Lyophilized products are typically hygroscopic and require protection from moisture during storage. Manufacturers seal them in glass vials, often under vacuum or an inert gas such as nitrogen. The container closure system, including the stopper and crimp seal, must prevent water vapor ingress. Storage temperature varies from controlled room temperature to refrigerated or frozen conditions, depending on the formulation. Humidity-controlled environments are essential because even brief exposure to ambient air can degrade the product.
Stability of a lyophilized product depends on its glass transition temperature, the temperature at which the amorphous cake transitions from a glassy to a rubbery state. Storage below this temperature minimizes molecular mobility and slows chemical degradation. If the storage temperature exceeds the glass transition temperature, the cake may collapse, shrink, or become sticky. Accelerated stability studies at elevated temperatures and humidity help predict shelf life, but they do not always reflect real-time behavior. Residual moisture content also plays a critical role in long-term stability.
Reconstitution involves adding a suitable diluent, often sterile water or a buffer, to the dried cake. Gentle swirling or inversion helps dissolve the material without creating excessive foam. The time required for complete dissolution can range from seconds to several minutes and depends on the cake structure and the diluent. Improper reconstitution, such as vigorous shaking or using the wrong diluent, can cause protein aggregation or loss of activity. After reconstitution, the product may have a limited shelf life and should be used according to its labeling.
| Property | Value | Notes |
|---|---|---|
| Common names | Lyophilization; freeze-drying | Terms used interchangeably. |
| Phase change | Sublimation | Ice converts directly to vapor under vacuum. |
| Typical chamber pressure | 0.01–1 mbar | Below the triple point of water. |
| Primary drying product temperature | −40 to −10 °C | Kept below collapse or glass transition temperature. |
| Water content after drying | 0.5–3% w/w | Varies with formulation and cycle. |
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.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
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.
After lyophilization, a product's quality depends on residual moisture, cake appearance, and reconstitution time. Residual moisture is often measured by Karl Fischer titration or thermogravimetric analysis. A low moisture content can slow chemical degradation, but overly dry cakes may be brittle or slow to dissolve. Stability studies track these attributes over months under defined temperature and humidity conditions. Batch records link these measurements to specific process runs and help identify trends before a product fails specification.
Storage conditions for dried products usually aim to exclude moisture and oxygen. Vials are sealed under vacuum or with an inert gas, and stoppers must maintain a barrier during transport. Temperature recommendations vary; some materials remain stable at room temperature, while others need refrigeration or frozen storage. Humidity control is critical because dried cakes can absorb water rapidly once a container is opened. Desiccant packs and moisture-barrier bags add further protection during shipping.
== Structure == Sulfonylureas contain a central S-arylsulfonylurea structure with a p-substituent on the phenyl ring (R1) and various groups terminating the urea N′ end group (R2). Chemically, this functionality can be easily installed by reacting aryl sulfonamides (R1—C6H4—SO2NH2) with isocyanates (R2—NCO).
== Precursor == Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids compared to the active enzyme. In the stomach, gastric chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining. The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested. Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin. Pepsinogens are mainly grouped in 5 different groups based on their primary structure: pepsinogen A (also called pepsinogen I), pepsinogen B, progastricsin (also called pepsinogen II and pepsinogen C), prochymosin (also called prorennin) and pepsinogen F (also called pregnancy-associated glycoprotein).
=== 2017 === On 29 September 2017, BSAT-4a, dedicated for UHDTV programming and was also claimed "the world's first 8K satellite", was launched from the Guiana Space Centre aboard Ariane 5 rocket. BSAT-4a would be used for 2020 Summer Olympics held in Japan. Additionally, in September 2017, Kaleidescape, a manufacturer of home-theater movie players and servers made 4K UHD movies compatible with their movie store, and with their movie players. In December 2017, Qualcomm announced that their Snapdragon 845 chipset and Spectra 280 Image Signal Processor would be the first phone SoC to record video in UHD Premium.
Sources: en.wikipedia.org
=== 2000 === 13 March The Secret Life of the Crash Test Dummy, about the biomechanics of car crashes; a typical crash test dummy cost around £100,000, with about three hundred individual parts, that had to be included by safety law, and new cars could not be sold until the dummy had tested it sufficiently; the Volvo 300 1980s television advert; Lt-Col Wayne Mattson of the USAF and a strange crash in New Mexico, one hundred miles north of the Trinity (nuclear test), and near White Sands Missile Range, where German V-2 missiles were being tested, which were conveniently blamed by the USAF on anthropomorphic dummies; John Melvin (engineer) and the legacy of USAF biophysicist and doctor Colonel John Stapp, who mostly invented aviation safety testing; John Stapp conducted gruesome horrific deceleration tests on himself; Alderson had made artificial limbs for injured USAF World War II pilots, so made a full artificial proto-human; John Stapp tested his dummies in vehicles; Clarence Ditlow and the Center for Auto Safety; in 1966 it became legal in the US for new cars to have been tested by dummies; mathematical models of injury were needed, to translate the acquired crash data into possible effects on the human body, worked out by mechanical engineer Walter Pilkey of the University of Virginia; Scottish orthopaedic surgeon Angus Wallace and impact speed on bone tensile strength; in 1976 the Hybrid III dummy was designed, the automotive industry standard design; David Abbott, advertising executive; the data for designing the crash test dummy, Hybrid III, was mostly derived from data procured for human male occupants - and typical (fiftieth percentile) males, not female, and females had much different bodies; child dummies were essentially smaller adult male dummies, which was not biologically true; new dummies were developed at the National Transportation Biomechanics Research Center. Narrated by Andrew Lincoln, produced by Cathy Rogers, directed by Peter Webber, made by RDF Television. Shown on Wednesday 17 January 2001 on The Nature of Things in Canada 20 March Rise and Fall of GM Food, about genetically modified food; Belgian geneticist Marc Van Montagu, of the University of Ghent, visits Havana in Cuba, where a new research centre opened with Carlos Borroto; protests by topless women; GM was largely first developed by Mexican geneticist Herrera Estrella, of the Centre of Investigation and Advanced Studies; Rob Fraley of Monsanto; US farmers spend $8bn dollars on herbicides and pesticides; Roger N. Beachy had a breakthrough in 1986 at the Washington University in St. Louis, now at the Donald Danforth Plant and Science Center; Monsanto made the first insecticide-resistant plant in 1987; many African farmers cannot afford insecticides; Cyrus Ndiritu of the Kenya Agriculture Research Institute; much food harvested in Africa does not last before it reaches the consumer; in 1990 Don Grierson of the Plant Science Division of the University of Nottingham found genes of ripening; Channapatna Prakash of Tuskegee University in Alabama; aluminium toxicity of soils in tropical countries affected yield; Julian Borger of The Guardian; biologist Mae-Wan Ho of the Open University; biologist John Gatehouse of the University of Durham, and the Pusztai affair at The Rowett Institute; Helen Browning, Chairman of the Soil Association; former Vice-Chancellor of UEA, Derek Burke; former Independent environment correspondent Richard D. North, who had grown out of love with the hard-line environmental movement; European farmers grew five times more produce than they did in the 1960s, and there were twice as many trees in the UK than in the 1920s; Renée Elliott of Planet Organic; around 100m children in Third World countries suffered from Vitamin A deficiency. Directed by Martin Durkin, made by his company Kugelblitz 27 March Simply Complex, about the physicist Murray Gell-Mann; by an accident, he devised strangeness of sub-atomic particles, in his mid-20s; he predicts an omega minus particle, which was found in 1962; he predicts that the proton and neutron were made of three triplet particles, which he called quarks from Finnegans Wake and his Eightfold way (physics), also predicted by George Zweig; he worked closely with Richard Feynman at Caltech in the 1960s; on 30 October 1969 he is told that he had won the Nobel Prize for Physics; his friendship with MIT mechanical engineer Seth Lloyd; British physicist Geoffrey West; the documentary is in a biographic informal style that Horizon has since often followed. Produced by Barbara Altounyan, directed by Celia Lowenstein, made by Diverse Productions 3 April Meningitis - Search for a Cure, 3,000 people in the UK had meningitis in 1999; microbiologist Martin C. J. Maiden; one in five died from meningococcal disease; damage is caused by the endotoxin (lipopolysaccharide); a healthy survey is carried out at Burford School; Mike Levin (paediatrician) at Imperial College, and how meningitis A is a huge danger in Africa; 60% of cases in the UK are meningitis B, and many such cases are treated at St Mary's Hospital, London; Brett Giroir of the Children's Medical Center Dallas; 17-year-old Amy Mansell from Whitstable was in a coma for five weeks. Narrated by Paul Brightwell, produced by David Dugan, directed by Jeremy Llewellyn-Jones, made by Windfall Films with Nova and WGBH Boston. It was shown on Nova as Killer Disease on Campus, episode 9 of season 29, shown on 3 September 2002, and shown under the original programme title as a half-hour programme on 6 November 2003 on Catalyst on ABC in Australia 10 April The Box, about flight recorders, with ValuJet Airlines Flight 592 which crashed on 11 May 1996; voice recorders have been compulsory since the late 1960s; Dukane Seacom make emergency underwater locator beacons (ULBs); the Boeing 737, which had around 21,000 take-offs per day, was believed to have unreliable rudder control since the 1980s, as shown in the United Airlines Flight 585 crash on 3 March 1991, having had two rudder incidents in the previous two weeks, with the aircraft flipping 35 seconds after take-off and crashing all in seven seconds; the electrohydraulic servo valve in the Boeing 737 rudder control unit was thought to be sometimes temperamental; Boeing claimed that the March 1991 crash was due to a rotor or lee wave, caused by nearby mountains; the USAir Flight 427 crash on 8 September 1994, where the aircraft flipped at 6,000 ft, in 28 seconds crashing; British Airways did not rely on their Penny & Giles quick access recorders, and would consolidate this data where anomalies were checked, so the NTSB needed BA's data for their 737 aircraft; this safer BA method was introduced by the previous British European Airways (BEA) when it had to prove to the CAA that its autoland system for the Trident was safe, in the Civil Aircraft Airworthiness Data Recording Programme which since 1990 has been collected by the British Airways Safety Information System (BASIS); the 1991 crash investigation concluded after 8 years in 1999, with Boeing ordered to redesign the servo valve. 9 October Full Throttle, about the technology and psychology of motor racing; Brazilian driver Christian Fittipaldi; the Eurofighter, controlled by computers, and due to enter RAF service in 2002; Archie Neill, BAE test pilot; Stephen Olvey, motor racing medical officer; driver Mark Blundell; the Long Beach Grand Prix in Los Angeles; Steve Clark, engineer for Mercedes; Brian Lisles and Peter Gibbons of Newman Haas Racing; the edge of performance envelope; Mario Andretti, former driver: Edward Winter of Sheffield Hallam University and predicting outcomes in sport, by intuition; John Rothwell of the Institute of Neurology in London, testing reflexes, by an MRI scanner, and how the brain stores instructions; psychologist Mike Land of the University of Sussex, and the psychology of prediction, and feedforward; life expectancy of racing drivers in the 1970s was short; racing drivers had risk positive personalities, and became accustomed to risk; psychologist Tim Wheeler; Jimmy Vasser of Chip Ganassi Racing; a female violinist plays La fille aux cheveux de lin; sports psychologist Brian Hemmings; Austrian driver Alexander Wurz of Benetton Formula; RAF SEPECAT Jaguar XZ103 of 41 Squadron; engineer Pat Symonds of Benetton Racing; Simon Taylor (journalist) of Motor Sport; Graham Rood of DERA Air Systems in north Hampshire. Narrated by Stephen Rashbrook, produced by Patrick Uden, directed by Andy Robbins, made by Uden Associates 16 October Lethal Seas: the Maelstrom, about ocean whirlpools; the Gulf of Corryvreckan in Scotland, Lofoten and Saltstraumen in Norway; with Prof Tsukasa Nishimura of Tokyo University of Science and Prof Walter Munk of the Scripps Institution of Oceanography; the Firth of Lorn in west Scotland has one of the world's most dangerous whirlpools, the Royal Navy avoids it; atmospheric physicist Peter Read; mathematician David Dritschel, and the Great Red Spot vortice; the dangerous Arran Rapids on the Cordero Channel in western Canada; Burkard Baschek of the Institute of Ocean Sciences, who dropped a CTD (instrument) into the torrential river currents; Tremble Island in the notorious Slingsby Channel, where a geophone was placed; the novel A Descent into the Maelström; Bjørn Gjevik, a fluid dynamicist in the Department of Mathematics, at the University of Oslo; strong tidal currents in the Naruto Strait in Japan, and the Naruto whirlpools. Narrated by Stephen Rashbrook, produced by Robert Sproul-Cran, directed by Kim Flitcroft, made by Northlight Productions with the Discovery Channel 23 October Einstein's Biggest Blunder, about calculations of the expansion of the universe; the documentary opens with a pastiche of the Star Wars opening credits; two physicists met in 1996, with a new radical proposal for explaining the many anomalies in the expansion of the universe - Andreas Albrecht (cosmologist) of the University of California, Davis and João Magueijo of Portugal; Dave Wark of the University of Sussex, visits Bern in Switzerland; Ruth Durrer of the University of Geneva; John E. Baldwin of the University of Cambridge, and the 1887 Michelson–Morley experiment, which found that the Earth's rotational speed did not affect the speed of light in any way, alongside the Venus movement of The Planets; to account for this, Einstein made his field equations, and lambda - the cosmological constant was added by Einstein to account for how space-time would need to expand; Einstein's equations inferred that the expansion of the universe rested on inherently unstable conditions; due to the Doppler effect, background radiation from the Big Bang is now perceived as microwave radiation; Richard Ellis (astronomer) of Caltech; Einstein didn't believe in the Big Bang until a meeting with Hubble in 1932 in California; with the new theory of an expanding universe, the cosmological constant was now required, but the precise trajectory of the expansion of the universe could not be directly predicted, which led to the flatness problem; the theory of inflation was put forward by Alan Guth in the 1970s; when at St John's College, Cambridge, João Magueijo had the radical proposal that if the speed of light was higher, in the early universe, a cosmological horizon of sufficient distance would be possible, to explain the predicted conditions of the expansion of the early universe, and the cosmological constant problem; the Royal Society gave him a research fellowship to work at Imperial College; as further exploratory work was clocked up, with calculations inclya variable speed of light, the team of physicists looked at other applications for their controversial proposals, such as the flatness problem, and what happened before the Big Bang; in 1998 astrophysicist John Webb, at the University of Cambridge, worked on the theory of a variable speed of light, through investigating quasars, the most distant objects that can be seen; and by looking at supernovae, it was largely expected that any recorded data would show indications of a deceleration in the rate of expansion of the universe, but the data instead showed that the rate of expansion was - increasing, which led to the lambda-CDM model. Narrated by Scottish actor Matthew Zajac, directed by David Sington, made by Dox Productions 30 October The Science of Stress, with 42-year-old actor Angus Kennedy; endocrinologist Stafford Lightman of the University of Bristol; Vivette Glover, a perinatal psychobiological at Imperial College; Sir Cary Cooper, psychologist at the former UMIST; Carolyn M. Mazure, psychiatrist at Yale School of Medicine; Charles Nemeroff, psychiatrist at Emory University School of Medicine. Narrated by Geoffrey Palmer, directed by Michael Samuels, produced by Bridget Sneyd, made by Lion Television and the Discovery Health Channel 7 December Science of Crime - Psychopath, with psychologists Robert D. Hare and Adrian Raine, about the psychopathic traits of insincere superficial charm, on the Psychopathy Checklist. Narrated by Neil Pearson, directed by John Purdie, produced by Rosalind Arden, made by Union Pictures 14 December Science of Crime - Criminal Evidence, about the forensic psychologist 49-year-old Kathy Reichs. Produced by Geoff Deehan, directed by Roger Pyke, made by Yap Films 21 December Science of Crime - Cybercops, the Hackers on Planet Earth conference; Cult of the Dead Cow, founded by Swamp Rat, and its Back Orifice software for accessing Windows 98; the Happy99 virus; wardialing; part of the High Technology Theft Apprehension and Prosecution Program in California. Narrated by Steven Mackintosh, written by Callum Macrae, directed by Witold Starecki
== Amino-acid sequences == Analysis of the suite of known cyclotides reveals many sequence similarities that are important for understanding their unique physico-chemical properties, bioactivities and homology. The cyclotides fall into two main structural subfamilies. Moebius cyclotides, the less common of the two, contain a cis-proline in loop 5 that induces a local 180° backbone twist (hence likening it to a Möbius strip), whereas bracelet cyclotides do not. There is smaller variation in sequences within these subfamilies than between them. A third subfamily of cyclotides are trypsin inhibitors and are more homologous to a family of non-cyclic trypsin inhibitors from squash plants known as knottins or inhibitor cystine knots than they are to the other cyclotides. It is convenient to discuss sequences in terms of the backbone segments, or loops, between successive cysteine residues. The six cysteine residues are absolutely conserved throughout the cyclotide suite and presumably contribute to preserving the CCK motif. Although the cysteines appear essential to maintaining the overall fold, several other residues highly conserved in cyclotides are thought to provide additional stability. Throughout the known cyclotides loop 1 is the most conserved. Apart from the six cysteine residues, the glutamic acid and serine/threonine residues of loop 1 are the only residues to have 100% identity across the bracelet and Möbius subfamilies. Furthermore, the remaining residue of this loop exhibits only a conservative change i.e. glycine/alanine.
Caution, however, is generally prudent when doing this, as seizures, which are more likely to occur with clomipramine than every other tricyclic antidepressant besides maprotiline, become more and more of a risk beyond the normally-recommended upper-ceiling. At daily doses ≤ 250 mg, the incidence of seizures may be reliably estimated to be around the order of 0.48%. (All tricyclic antidepressants technically lower the seizure-threshold but this is only significant with amoxapine, maprotiline and, indeed, clomipramine.) Dose-increases between 25 mg and 150 mg, barring significant drug-drug interactions which may elevate clomipramine blood-levels, should be titrated in doses of 50 mg (25 mg in the case of panic disorder and 10 to 25 mg in the cases of premature ejaculation and narcoleptic cataplexy) and above 150 mg in 25 mg increments. Average optimal total daily doses for depression (whether mild or severe), premature ejaculation, cataplexy-narcolepsy, obsessive–compulsive disorder, panic disorder and trichotilomania respectively are (in milligrams) 150, 50, 25 - 75, 150 - 250, 50 - 150 and 150 - 200. Some consider the minimum optimally-therapeutic dose of clomipramine in obsessive-compulsive disorder, which often requires much higher levels of serotonergic concentration than other indications for these drugs, to be 200, rather than 150, milligrams per day. For premature ejaculation, clomipramine can be taken prn 3 to 5 hours before attempted sexual intercourse.
Sources: en.wikipedia.org
Yes. Lyophilization and freeze-drying are synonyms for the same vacuum-assisted sublimation process. The term lyophilization is more common in pharmaceutical and laboratory settings, while freeze-drying is widely used in food and general contexts.
Reduced pressure lowers the boiling point of water and allows ice to sublime below its triple point. Without sufficient vacuum, melting or boiling may occur instead of sublimation, which can damage the product structure.
Heat and mass transfer limit drying once the ice front recedes. The dried layer insulates the frozen core and resists vapor flow, so increasing shelf temperature too quickly can cause collapse or meltback.
Lyophilized products should be stored in airtight containers, protected from moisture and light, at the temperature specified by the manufacturer. Many require refrigeration at 2–8 °C, while some need frozen storage. Always check the product label for specific conditions.