A practical reference on Lyophilization: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2025-09-12. Anything still debated is marked as such rather than presented as settled.
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.
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.
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.
| 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 |
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.
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.
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.
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.
== Further reading == Feldman and Pike's Vitamin D (5th Edition) Volume One: Biochemistry, Physiology and Diagnostics; Editors: Hewison M, Bouillon R, Giovannucci E, Goltzman D, Meyer MB, Welsh J. Academic Press (October 2023) ISBN 978-0-32-391386-7 Feldman and Pike's Vitamin D (5th Edition) Volume Two: Diseases and Therapeutics; Editors: Hewison M, Bouillon R, Giovannucci E, Goltzman D, Meyer MB, Welsh J. Academic Press (January 2024) ISBN 978-0-32-391338-6 Dietary Reference Intakes for Vitamin D and Calcium Editors: Ross AC, Taylor CL, Yaktine AL, Del Valle HB. National Academies Press (US) (2011) ISBN 978-0-30-916394-1 Available from: Dietary Reference Intakes for Calcium and Vitamin D doi: 10.17226/13050
Although it is not acknowledged in Psychological Types, it is likely that Jung's theory of psychological types was influenced by Alfred Binet's distinction between two intellectual attitudes: 'introspection' and 'externospection'.
They acknowledged that kimchi and pao cai are two different foods, where "Kimchi refers to a kind of fermented cabbage dish that plays an integral role in Korean cuisine, while pàocài, or Sichuan pàocài, refers to pickled vegetables that are popular originally in Southwest China's Sichuan Province, but now in most parts of northern China." Global Times also reported that Baidu Baike, a Chinese online encyclopedia, removed the controversial phrase "Korean kimchi originated from China" after the request. According to Sojin Lim, co-director of the Institute of Korean Studies of the University of Central Lancashire, Korean kimchi is often called pao cai in China, but China has its own Sichuanese fermented vegetable dish that it also calls pao cai. In 2021, the South Korean Ministry of Culture, Sports and Tourism subsequently presented the guidelines to set the term xīnqí (辛奇) as the new proper Chinese translation of kimchi, while pàocài was no longer the acceptable translation. However, CNN reported that the new Chinese translation of kimchi was unpopular with both Chinese and Korean netizens, and that some Chinese people complained that they do recognize the difference between dishes, but do not like to be told how to translate Kimchi in Chinese. There were also complaints among Koreans that Korea is appropriating their own traditional culture for the Chinese, by trying to promote a Chinese term for Kimchi which does not have an authentic Korean sound.
In October 1938, Joachim von Ribbentrop first proposed German-Polish territorial adjustments and Poland's participation in the Anti-Comintern Pact against the Soviet Union. The status of the Free City of Danzig was one of the key bones of contention. Approached by Ribbentrop again in March 1939, the Polish government expressed willingness to address issues causing German concern, but effectively rejected Germany's stated demands and thus refused to allow Poland to be turned by Adolf Hitler into a German puppet state. Hitler, incensed by the British and French declarations of support for Poland, abrogated the German–Polish declaration of non-aggression in late April 1939. To protect itself from an increasingly aggressive Nazi Germany, already responsible for the annexations of Austria (in the Anschluss of 1938), Czechoslovakia (in 1939) and a part of Lithuania after the 1939 German ultimatum to Lithuania, Poland entered into a military alliance with Britain and France (the 1939 Anglo-Polish military alliance and the Franco-Polish alliance (1921), as updated in 1939). However, the two Western powers were defense-oriented and not in a strong position, either geographically or in terms of resources, to assist Poland. Attempts were therefore made by them to induce Soviet-Polish cooperation, which they viewed as the only militarily viable arrangement. Diplomatic manoeuvers continued in the spring and summer of 1939, but in their final attempts, the Franco-British talks with the Soviets in Moscow on forming an anti-Nazi defensive military alliance failed.
When served neat (without any additional ingredients), tequila is most often served in a narrow shot glass called a caballito (little horse in Spanish), but can often be found in anything from a snifter to a tumbler. The Consejo Regulador del Tequila approved an "official tequila glass" in 2002 called the Ouverture Tequila glass, made by Riedel. The margarita glass, frequently rimmed with salt or sugar, is a staple for the entire genre of tequila-based mixed drinks, including the margarita.
Sources: en.wikipedia.org
== Advantages == MIKES, as the name implies, is used for kinetic energy spectrometery. This means that certain criteria are needed to accomplish this. One such feature of MIKES is that it has high kinetic energy resolution and good angular resolution. This is due to the fact that MIKES has low accelerating voltage, around 3 kilo-volts. Another feature is that it has good differential pumping between the various regions of the instrument. In addition, MIKES has multiple systems for bringing in and/or overseeing collision gases or vapors and the ability to vary slit height and width. This prevents favoritism when determining kinetic energy distributions. Although common now, back in the 1970s, MIKES had a great computer compatibility that allowed for readily obtainable molecular structures.
In May 2014, researchers announced that they had successfully introduced two new artificial nucleotides into bacterial DNA, and by including individual artificial nucleotides in the culture media, were able to induce amplification of the plasmids containing the artificial nucleotides by a factor of 2 × 107 (24 doublings); they did not create mRNA or proteins able to use the artificial nucleotides.
The US Navy dispatched two naval battle groups built around the aircraft carriers USS Dwight D. Eisenhower and USS Independence to the Gulf, where they were ready by 8 August. The US sent the battleships USS Missouri and USS Wisconsin. 48 US Air Force F-15s from the 1st Fighter Wing at Langley Air Force Base, Virginia, landed in Saudi Arabia and commenced round-the-clock air patrols of the Saudi–Kuwait–Iraq border to discourage Iraqi military advances. They were joined by 36 F-15 A-Ds from the 36th Tactical Fighter Wing at Bitburg, Germany. The Bitburg contingent was based at Al Kharj Air Base. The 36th TFW would be responsible for 11 confirmed Iraqi Air Force aircraft shot down during the war. Two Air National Guard units were stationed at Al Kharj Air Base, the South Carolina Air National Guard's 169th Fighter Wing flew bombing missions with 24 F-16s flying 2,000 combat missions and dropping four million pounds (1,800,000 kilograms; 1,800 metric tons) of munitions, and the New York Air National Guard's 174th Fighter Wing from Syracuse flew 24 F-16s on bombing missions. Military buildup continued, reaching 543,000 troops, twice that used in the 2003 invasion. Much of the material was airlifted or carried to the staging areas via fast sealift ships, allowing a quick buildup. Amphibious exercises were carried out in the Gulf, including Operation Imminent Thunder, which involved the USS Midway and 15 other ships, 1,100 aircraft, and a thousand Marines.
==== Larva ==== Cabbage looper larvae are a type of cabbage worm, green in colour with a white stripe on the side. After hatching, they are green and slightly hairy, but eventually turn green and lose the hair, leaving only a few bristles. They are identified by their looping behaviour, in which they arch their body in a loop when they crawl. Larvae are generally 3–4 cm long, and can have four to seven instars within 9–14 days. Larvae initially do not consume much food but increase their consumption during their lifetime until they are consuming three times their weight daily.
Sources: en.wikipedia.org
=== EC 1.3.99 With unknown physiological acceptors === EC 1.3.99.1: The activity is included in EC 1.3.5.1, succinate dehydrogenase (quinone) EC 1.3.99.2: Now EC 1.3.8.1, butyryl-CoA dehydrogenase. EC 1.3.99.3: now EC 1.3.8.7, medium-chain acyl-CoA dehydrogenase, EC 1.3.8.8, long-chain acyl-CoA dehydrogenase and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase EC 1.3.99.4: 3-oxosteroid 1-dehydrogenase EC 1.3.99.5: 3-oxo-5α-steroid 4-dehydrogenase (acceptor) EC 1.3.99.6: 3-oxo-5β-steroid 4-dehydrogenase EC 1.3.99.7: Now EC 1.3.8.6, glutaryl-CoA dehydrogenase EC 1.3.99.8: 2-furoyl-CoA dehydrogenase EC 1.3.99.9: Now EC 1.21.99.1, β-cyclopiazonate dehydrogenase EC 1.3.99.10: Now EC 1.3.8.4, isovaleryl-CoA dehydrogenase EC 1.3.99.11: transferred to EC 1.3.5.2, dihydroorotate dehydrogenase EC 1.3.99.12: Now classified as EC 1.3.8.5, 2-methyl-branched-chain-enoyl-CoA reductase EC 1.3.99.13: Now EC 1.3.8.8, long-chain-acyl-CoA dehydrogenase EC 1.3.99.14: cyclohexanone dehydrogenase EC 1.3.99.15: Now EC 1.3.7.8 EC 1.3.99.16: isoquinoline 1-oxidoreductase EC 1.3.99.17: quinoline 2-oxidoreductase EC 1.3.99.18: quinaldate 4-oxidoreductase EC 1.3.99.19: quinoline-4-carboxylate 2-oxidoreductase EC 1.3.99.20: Now EC 1.3.7.9, 4-hydroxybenzoyl-CoA reductase EC 1.3.99.21: Now EC 1.3.8.3, (R)-benzylsuccinyl-CoA dehydrogenase EC 1.3.99.22: Now EC 1.3.98.3, coproporphyrinogen dehydrogenase EC 1.3.99.23: all-trans-retinol 13,14-reductase EC 1.3.99.24: Now EC 1.3.8.16, 2-amino-4-deoxychorismate dehydrogenase EC 1.3.99.25: carvone reductase EC 1.3.99.26: all-trans-ζ-carotene desaturase EC 1.3.99.27: 1-hydroxycarotenoid 3,4-desaturase EC 1.3.99.28: phytoene desaturase (neurosporene-forming) EC 1.3.99.29: phytoene desaturase (zeta-carotene-forming) EC 1.3.99.30: phytoene desaturase (3,4-didehydrolycopene-forming) EC 1.3.99.31: phytoene desaturase (lycopene-forming) EC 1.3.99.32: glutaryl-CoA dehydrogenase (non-decarboxylating) EC 1.3.99.33: urocanate reductase EC 1.3.99.34: Now classified as EC 1.3.7.11, 2,3-bis-O-geranylgeranyl-sn-glycero-phospholipid reductase EC 1.3.99.35: Now EC 1.3.7.15, chlorophyllide a reductase * EC 1.3.99.36: cypemycin cysteine dehydrogenase (decarboxylating) EC 1.3.99.37: 1-hydroxy-2-isopentenylcarotenoid 3,4-desaturase EC 1.3.99.38: menaquinone-9 β-reductase EC 1.3.99.39: carotenoid φ-ring synthase EC 1.3.99.40: carotenoid χ-ring synthase
Generally, physicians, dentists, physiotherapists, nurses, paramedics, radiographers, and students of certain biological sciences, learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures, and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical and dental students generally also learn anatomy with practical experience of dissection and inspection of cadavers (dead human bodies). A thorough working knowledge of anatomy is required for all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology. Human anatomy, physiology, and biochemistry are basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically; that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Gray's Anatomy, has recently been reorganized from a systems format to a regional format, which is in line with the modern teaching.
L-Arginine:glycine amidinotransferase (AGAT; EC 2.1.4.1) is the enzyme that catalyses the transfer of an amidino group from L-arginine to glycine. The products are L-ornithine and glycocyamine, also known as guanidinoacetate, the immediate precursor of creatine. Creatine and its phosphorylated form play a central role in the energy metabolism of muscle and nerve tissues. Creatine is in highest concentrations in the skeletal muscle, heart, spermatozoa and photoreceptor cells. Creatine helps buffer the rapid changes in ADP/ATP ratio in muscle and nerve cells during active periods. Creatine is also synthesized in other tissues, such as pancreas, kidneys, and liver, where amidinotransferase is located in the cytoplasm, including the intermembrane space of the mitochondria, of the cells that make up those tissues.
==== Cyanobacteria ==== Cyanobacterial CCMs are similar in principle to those found in eukaryotic algae and hornworts, but the compartment into which carbon dioxide is concentrated has several structural differences. Instead of the pyrenoid, cyanobacteria contain carboxysomes, which have a protein shell, and linker proteins packing RuBisCO inside with a very regular structure. Cyanobacterial CCMs are much better understood than those found in eukaryotes, partly due to the ease of genetic manipulation of prokaryotes.
=== Removing plastics from oceans === One innovation of green nanotechnology that is currently under development are nanomachines modeled after a bacterium bioengineered to consume plastics, Ideonella sakaiensis. These nano-machines are able to decompose plastics dozens of times faster than the bioengineered bacteria not only because of their increased surface area but also because the energy released from decomposing the plastic is used to fuel the nano-machines.
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.
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.