Everything below concerns primary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-02-07. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
A typical cycle begins with freezing, sometimes including an annealing step to control ice crystal size. Freezing conditions influence the pore network that later allows vapor escape. During primary drying, shelf temperature and chamber pressure are set so heat enters the product while its temperature stays below the collapse or eutectic point. Secondary drying then raises the shelf temperature to desorb bound water and lower residual moisture. Cycle design depends on formulation, fill volume, container type, and equipment capability.
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.
| 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. |
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.
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.
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 process relies on the phase diagram of water, where the triple point marks the conditions at which ice, liquid water, and vapor coexist. By maintaining pressure below this point, typically around 0.01 to 0.1 millibar, sublimation becomes the dominant mechanism. Formulations often include excipients such as sugars or polymers that act as lyoprotectants and bulking agents. These additives help preserve the structure of the active ingredient and prevent collapse during drying. The choice of excipient and freezing rate influences the final cake morphology and stability.
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.
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.
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.
mobile genetic element (MGE) Any genetic material that can move between different parts of a genome or be transferred from one species or replicon to another within a single generation. The many types of MGEs include transposable elements, bacterial plasmids, bacteriophage elements which integrate into host genomes by viral transduction, and self-splicing introns.
=== Films === The Devil We Know (2018): a documentary detailing the health dangers of PFAS. Dark Waters (2019): a thriller movie based on the corporate defense of PFAS and DuPont. Contaminated: The Carpet Industry's Toxic Legacy (2026): documentary about the history of PFAS and the carpet industry. Everywhere & Forever: Blood. Water. And the Politics of PFAS (2025): a documentary about PFAS and the struggles to manage the contamination. Revealed: How to Poison A Planet (2024): a documentary detailing the negative externalities from PFAS creation.
== Synthesis == Chymopapain is no longer used as a standard method to treat chronic low back pain because of its potential side effects. Therefore, there is no need to synthesize it artificially. In fact, the sale and distribution of this protein was discontinued in the US in 2003. Despite the huge amount of successful use to treat herniated disk disease, chymopapain use was discontinued not because of hazards or inadequacies but rather because it is no longer available due to a decision by its sole manufacturer to stop production. However, several studies have demonstrated different successful methods to extract and isolate the protease, which vary among authors. The most common procedure is the one described by Baines & Brocklehurst in 1979. In order to obtain the protein, Carica Papaya fruits are used, as chymopapain is found in its latex. The papayas should be just in the previous step before maturation, which implies an average diameter of 6–10 cm.
George W. Bush Presidential Library and Museum White House biography Full audio of a number of Bush speeches Appearances on C-SPAN George W. Bush collected news and commentary at The New York Times Archived White House website Collection of George W. Bush's works on the Troubled Asset Relief Program George W. Bush at IMDb Works by George W. Bush at Project Gutenberg
Sources: en.wikipedia.org
=== Kodesomes === Kodesomes are liposomes that have been decorated with FSL Kode constructs. These have been used to deposit FSL constructs onto microplates to create diagnostic assays. They also have the potential for therapeutic use.
On 5 October 1959, Trieste departed San Diego for Guam aboard the freighter Santa Maria to participate in Project Nekton, a series of very deep dives in the Mariana Trench. On 23 January 1960, Trieste reached the ocean floor in the Challenger Deep (the deepest southern part of the Mariana Trench), carrying Jacques Piccard (son of Auguste) and Lieutenant Don Walsh, USN. This was the first time a vessel, crewed or uncrewed, had reached the deepest point in the Earth's oceans. The onboard systems indicated a depth of 11,521 metres (37,799 ft), although this was later revised to 10,916 metres (35,814 ft) and more accurate measurements made in 1995 have found the Challenger Deep slightly shallower, at 10,911 metres (35,797 ft). Building a pressure hull is difficult, as it must withstand pressures at its required diving depth. When the hull is perfectly round in cross-section, the pressure is evenly distributed, and causes only hull compression. If the shape is not perfect, the hull deflects more in some places and buckling instability is the usual failure mode. Inevitable minor deviations are resisted by stiffener rings, but even a one-inch (25 mm) deviation from roundness results in over 30 percent decrease of maximal hydrostatic load and consequently dive depth. The hull must therefore be constructed with high precision. All hull parts must be welded without defects, and all joints are checked multiple times with different methods, contributing to the high cost of modern submarines.
An analgesic, also called an antalgic, painkiller, or pain reliever, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects. Analgesic choice is also determined by the type of pain: For neuropathic pain, recent research has suggested that classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants may be considered as an alternative. Various analgesics, such as many NSAIDs, are available over the counter in most countries, whereas various others are prescription drugs owing to the substantial risks and high chances of overdose, misuse, and addiction in the absence of medical supervision.
In bioconjugation (forming a stable covalent link between a biomolecule and a functional payloads, such as fluorescent dyes, cytotoxic agents, or tracers), linking of the payload was classically achieved using maleimide heterobifunctional reagents (for example, see SMCC). However, when administered into living organisms, maleimide-containing bioconjugates were found to be relatively unstable and lose the payload in the blood circulation due to reversibility of the addition reaction between maleimide moiety and cysteine residue of a protein (retro Michael addition). Due to increased stability of bioconjugates obtained with analogous APN-based payloads (a schematic reaction is shown in the Figure 2 below), their use is often preferable when high selectivity and biostability are especially important: namely for the preparation of antibody−drug conjugates and other biologics. Standard procedure for APN protein labeling consists in incubation of a protein containing free cysteine residues with an APN-functionalized probe in PBS buffer at pH 7.5-9.0 at room temperature for 2–12 hours, followed by an optional step of purification of the resulting bioconjugate using size exclusion chromatography or ultrafiltration.
In rare susceptible individuals, midazolam has been known to cause a paradoxical reaction, a well-documented complication with benzodiazepines. When this occurs, the individual may experience anxiety, involuntary movements, aggressive or violent behavior, uncontrollable crying or verbalization, and other similar effects. This seems to be related to the altered state of consciousness or disinhibition produced by the drug. Paradoxical behavior is often not recalled by the patient due to the amnesia-producing properties of the drug. In extreme situations, flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose. Midazolam is known to cause respiratory depression. In healthy humans, 0.15 mg/kg of midazolam may cause respiratory depression, which is postulated to be a central nervous system (CNS) effect. When midazolam is administered in combination with fentanyl, the incidence of hypoxemia or apnea becomes more likely. Although the incidence of respiratory depression/arrest is low (0.1–0.5%) when midazolam is administered alone at normal doses, the concomitant use with CNS acting drugs, mainly analgesic opiates, may increase the possibility of hypotension, respiratory depression, respiratory arrest, and death, even at therapeutic doses. Potential drug interactions involving at least one CNS depressant were observed for 84% of midazolam users who were subsequently required to receive the benzodiazepine antagonist flumazenil.
Sources: en.wikipedia.org
X-Ray crystal-structure analysis of plastocyanin at 2.7 Å resolution --- 707 citations Guss, J. M.; Freeman, H. C. (1983). "Structure of oxidised poplar plastocyanin at 1.6 Å resolution". J. Mol. Biol. 169 (2): 521–563. doi:10.1016/S0022-2836(83)80064-3. PMID 6620385. --- 642 citations Guss, J. M.; Harrowell, P. R.; Murata, M.; Norris, V. A.; Freeman, H. C. (1986). "Crystal structure analyses of reduced (CuI) poplar plastocyanin at 6 pH values". J. Mol. Biol. 192 (2): 361–387. doi:10.1016/0022-2836(86)90371-2. PMID 3560221. --- 388 citations Guss, J. M.; Bartunik, H. D.; Freeman, H. C. (1992). "Accuracy and precision in protein-structure analysis: restrained least-squares refinement of the structure of poplar plastocyanin at 1.33 Å resolution". Acta Crystallogr. B. 48 (6): 790–811. Bibcode:1992AcCrB..48..790G. doi:10.1107/S0108768192004270. PMID 1492962. --- 257 citations Kumar, V.; Dooley, D. M.; Freeman, H. C.; Guss, J. M.; Harvey, I.; McGuirl, M. A.; Wilce, M. C. J.; Zubak, V. M. (1996). "Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 Å resolution". Structure. 4 (8): 943–955. doi:10.1016/S0969-2126(96)00101-3. PMID 8805580. --- 209 citations
=== Trademark disputes === A trademark dispute involving the owners of an unrelated restaurant also named Burger King in Mattoon, Illinois, led to a federal lawsuit. As a result, the larger Burger King chain was ordered not to build any franchises within a 20-mile radius of the Mattoon Burger King. An existing trademark held by a shop of the same name in South Australia forced the company to change its name in Australia to "Hungry Jack's", while another state trademark in Texas forced the company to abandon its signature product, the Whopper, in several counties around San Antonio. The company was only able to enter northern Alberta, in Canada, in 1995, after it paid the founders of another chain named Burger King.
==== Other exercise types ==== A 2021 meta-analysis found that meditative exercise programs (tai chi, yoga, qigong) were superior to other forms of exercise (aerobic, flexibility, resistance) in improving sleep quality. Other meta-analyses also found positive effects of tai chi for sleep, fibromyalgia symptoms, and pain, fatigue, depression and quality of life. These tai chi interventions frequently included 1-hour sessions practiced 1–3 times a week for 12 weeks. Meditative exercises, as a whole, may achieve desired outcomes through biological mechanisms such as antioxidation, anti-inflammation, reduction in sympathetic activity, and modulation of glucocorticoid receptor sensitivity. Several reviews and meta-analyses suggest that aquatic training can improve symptoms and wellness in people with fibromyalgia. It is recommended to practice aquatic therapy at least twice a week using a low to moderate intensity. However, aquatic therapy does not appear to be superior to other types of exercise. Combinations of different exercises, such as flexibility and aerobic training, may improve stiffness. However, the evidence is of low-quality. It is not clear if flexibility training alone, compared to aerobic training, is effective at reducing symptoms or has any adverse effects. According to a 2017 systematic review it is uncertain whether vibration training in combination with exercise may improve pain, fatigue, and stiffness.
can be defined in terms of stress and strain components which are averaged over a volume large compared with the distance between the suspended particles, but small with respect to macroscopic dimensions. Such suspensions generally exhibit non-Newtonian behavior. However, for dilute systems in steady flows, the behavior is Newtonian and expressions for
Carlos Manuel de Céspedes was either initiated or introduced to the concept of Freemasonry during his time studying in Spain the 1840's, but as well, he studied what secret societies he could of the entire Mediterranean region from Syria to Turkey on his travels. After the death of Narciso López, in 1851, de Céspedes wrote the original version of La Bayamesa with the poet José Fornaris. In 1867, de Céspedes joined Estrella Tropical Lodge No. 19, in the town of Bayamo. Most records indicate that this was his initiation. On August 13, 1867, a meeting was held at Estrella Tropical Lodge No. 19 to discuss the revolution against the Spanish. After the meeting, Francisco Maceo Osorio turned to Perucho Figueredo, and said to him: "...now it's your turn, who are a musician, to compose our own Marseillaise." Figueredo finished the instrumental composition the next day, on August 14. On October 20, 1868, Figueredo finished the lyrics of the current version of Cuba's national anthem as the revolutionary troops entered Bayamo.
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.
Freezing only converts liquid to solid. Lyophilization adds vacuum and controlled warming so frozen solvent sublimes, leaving a dry porous solid. The two steps are related but not interchangeable.