This is a working overview of Primary drying, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-13. Anything still debated is marked as such rather than presented as settled.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
In practice, lyophilization is slower and more energy intensive than simple drying. Cycle times can range from hours to several days depending on load, container, and formulation. Amorphous materials may require excipients that help preserve structure during freezing and drying. The method is widely used for biological materials, pharmaceuticals, and foods where heat drying would cause unacceptable change. Open questions remain about scaling cycles between laboratory and production equipment, and this gap affects technology transfer.
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.
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.
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.
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.
In November 15, 2024, Valve released an update to Half-Life 2: Deathmatch for the first time in 3 years, fixing bugs and adding additional fixes to maps. In February 18, 2025, the game was upgraded from 32-bit to 64-bit binaries for x64 systems, the update also included a number of minor graphical and quality-of-life fixes, along with major bug fixes.
These developments led to advances in the field of evolutionary developmental biology towards understanding how the various body plans of the animal phyla have evolved and how they are related to one another. The Human Genome Project—the largest, most costly single biological study ever undertaken—began in 1988 under the leadership of James D. Watson, after preliminary work with genetically simpler model organisms such as E. coli, S. cerevisiae and C. elegans. Shotgun sequencing and gene discovery methods pioneered by Craig Venter—and fueled by the financial promise of gene patents with Celera Genomics— led to a public–private sequencing competition that ended in compromise with the first draft of the human DNA sequence announced in 2000.
Vitamin B6 is a water-soluble vitamin, one of the B vitamins. The vitamin actually comprises a group of six chemically related compounds, i.e., vitamers, that all contain a pyridine ring as their core. These are pyridoxine, pyridoxal, pyridoxamine, and their respective phosphorylated derivatives pyridoxine 5'-phosphate, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. Pyridoxal 5'-phosphate has the highest biological activity, but the others are convertible to that form. Vitamin B6 serves as a co-factor in more than 140 cellular reactions, mostly related to amino acid biosynthesis and catabolism, but is also involved in fatty acid biosynthesis and other physiological functions.
4,500 Boers surrendered and much equipment was captured, but as with Roberts's drive against Kruger, these losses were of relatively little consequence, as the hard core of the Boer armies and their most determined and active leaders remained at large. From the Basin, Christiaan de Wet headed west. Although hounded by British columns, he succeeded in crossing the Vaal into western Transvaal, to allow Steyn to travel to meet their leaders. There was much sympathy for the Boers in Europe. In October, President Kruger and members of the Transvaal government left Portuguese East Africa on the Dutch warship De Gelderland, sent by the Queen Wilhelmina of the Netherlands. Paul Kruger's wife, however, was too ill to travel and remained in South Africa where she died on 20 July 1901 without seeing her husband again. President Kruger first went to Marseille and then to the Netherlands, where he stayed before moving to Clarens, Switzerland, where he died in exile in 1904.
Sources: en.wikipedia.org
Khloé Alexandra Kardashian (; born June 27, 1984) is an American media personality, socialite, and businesswoman. She rose to fame starring with her family in the reality television series Keeping Up with the Kardashians from 2007 to 2021. Its success led to the creation of spin-offs, including Kourtney and Khloé Take Miami (2009–2013) and Kourtney and Khloé Take The Hamptons (2014–2015). Following the ending of their previous show, she and her family began starring on Hulu's The Kardashians in 2022. From September 2009 to December 2016, Kardashian was married to basketball player Lamar Odom, whom she married one month after they first met. They starred in their own reality television series, Khloé & Lamar (2011–2012). In 2009, Kardashian participated in the second season of The Celebrity Apprentice, finishing 10th of 16 candidates after being fired by Donald Trump. In 2012, she co-hosted the second season of the American adaptation of The X Factor with actor Mario Lopez. In 2016, Kardashian hosted her own talk show, Kocktails with Khloé. She starred in and produced health and fitness docu-series Revenge Body with Khloé Kardashian from 2017 to 2019. In 2025, she began hosting her own weekly podcast called Khloe in Wonderland. Kardashian has been involved in the retail and fashion industries with her sisters Kourtney and Kim. They have launched several clothing collections and fragrances, and additionally released the book Kardashian Konfidential in 2010. The Dash boutique employees starred in their own short-lived reality television series, Dash Dolls (2015).
was renamed Merck Sharp & Dohme, and Schering-Plough renamed as "Merck & Co., Inc." The maneuver was an attempt to avoid a "change-of-control" in order to preserve Schering-Plough's rights to market Remicade. A settlement with Johnson & Johnson was reached in 2011, in which Merck agreed to pay $500 million. Merck Sharp & Dohme remains a subsidiary of the Merck & Co. parent. Richard Clark retired as CEO and company president in October 2011 and Kenneth Frazier became CEO. In October 2013, Merck announced it would cut 8,500 jobs in an attempt to cut $2.5 billion from its costs by 2015. Combined with 7,500 job cuts announced in 2011 and 2012, the layoffs amounted to 20% of its workforce. By 2014, research performed at Merck has led to U.S. FDA approval of 63 new molecular entities. In August 2014, Merck acquired Idenix Pharmaceuticals for $3.85 billion. In September 2014, the US Food and Drug Administration (FDA) approved Pembrolizumab (MK-3475) as a breakthrough therapy for melanoma treatment. In clinical trials, pembrolizumab provided partial tumor regression in about one quarter of patients, many of whom have not seen further progression of their disease in over 6 months of follow-up. In December 2014, the company acquired Swiss biotechnology company OncoEthix for up to $375 million. Between 2010 and 2015, the company cut around 36,450 jobs. During that time, the company sold its consumer health business to Bayer and narrowed the company's focus to immunology, vaccines, diabetes, emerging markets and medicines used in hospitals, like certain antibiotics.
coli bacteria stores proteins and pyrophosphates in its periplasmic membrane until either are needed within the cell. Recent advancement in phosphoproteomic identification has resulted in the discoveries of countless phosphorylation sites in proteins. This required an integrative medium for accessible data in which known phosphorylation sites of proteins are organized. A curated database of dbPAF was created, containing known phosphorylation sites in H. sapiens, M. musculus, R. norvegicus, D. melanogaster, C. elegans, S. pombe and S. cerevisiae. The database currently holds 294,370 non-redundant phosphorylation sites of 40,432 proteins. Other tools of phosphorylation prediction in proteins include NetPhos for eukaryotes, NetPhosBac for bacteria, and ViralPhos for viruses.
=== 1980–2009: Expansion globally === As the Japanese economy worsened in the 1980s, Ajinomoto sought to outsource more of its production overseas, which increased the number of employees the company employed overseas from 4,000 in 1979 to more than 11,000 in 1996. Starting in 1980, Ajinomoto began to refocus its diversification efforts from food products to its amino acid business. Following the US FDA's re-approval of aspartame in 1981, Ajinomoto began producing the sweetener at its Tokai factory in 1982. In 1987, Ajinomoto began researching drug development in the fields of clinical nutrition, anti-cancer drugs, infectious diseases, and cardiovascular drugs. Through this research, the company developed ELENTAL for use in clinical nutrition, LIVACT to fight liver disease, and Lentinan in collaboration with the Japanese Foundation for Cancer Research. Ajinomoto later released JINO as a cosmetic and amino acid for athletes, followed by Amino Vital, a supplement to JINO released in 1995. In 2000, Ajinomoto acquired NutraSweet and Euro-Aspartame from Monsanto. In December 1995, Ajinomoto's Philippine CEO and President Leonardo K. Ty was assassinated by two members of the communist guerrilla group Alex Boncayao Brigade. The group cited Ty's allegedly poor safety standards for one of his other companies that they claimed to have led to the deaths of several of his employees. Ty had been head of Union Ajinomoto Inc. with his brother Alejandro since the late 1960s, and prior to his death, Ty had been seeking the protection of the National Bureau of Investigation.
After the fall of Tripoli in August 2011, only a few towns in western Libya such as Bani Walid, Sebha, and Sirte remained Gaddafist strongholds. Gaddafi was reportedly planning to catch up with his Sebha commander Ali Kanna's Tuareg forces and seek asylum in Burkina Faso. Instead, Gaddafi retreated to his hometown of Sirte, where he convened a meeting with his son Mutassim and intelligence chief Abdullah Senussi and learned that his youngest son Khamis had been killed by a NATO airstrike on 29 August. In the weeks that followed, Gaddafi continued to broadcast defiant audio messages through Syria-based Arrai TV. On 10 September, General Massoud Abdel Hafiz announced the formation of the Republic of Fezzan in Sebha, where Gaddafi would be president for life. Sebha fell on 22 September. Surrounding himself with bodyguards and a small entourage, including Mutassim, security chief Mansour Dhao, and defense minister Abu-Bakr Yunis Jabr, Gaddafi continually changed residences to escape NATO and NTC shelling, devoting his days to prayer and reading the Qur'an. On 20 October, Gaddafi recorded a farewell audio message for his family, later publicized by Al-Hadath, and then broke out of Sirte's District 2 in a joint civilian-military convoy. According to Dhao, it was a "suicide mission" as Gaddafi wanted to die in the Jarref Valley, close to where he was born. At around 08:30, NATO bombers attacked, destroying at least 14 vehicles and killing at least 53 people.
Sources: en.wikipedia.org
American biochemist and geneticist at the NIH, who showed that UUU codes for phenylalanine, the first step in deciphering the genetic code. Nobel Prize in Physiology or Medicine (1968). Member Natl. Acad. Sci. USA. Roland Victor Norris (1888–1950). British biochemist at the Indian Institute of Science, who worked on glycogen metabolism and yeast fermentation, and later pioneered biochemistry in India. Paul Nurse FRS (President) (b. 1949). British geneticist at the Rockefeller University, who worked on control of the cell cycle. Nobel Prize in Physiology or Medicine (2001)
==== Enamel hypoplasia ==== Enamel hypoplasia refers to transverse furrows or pits that form in the enamel surface of teeth when the normal process of tooth growth stops, leaving a deficit. Enamel hypoplasias generally form due to disease and/or poor nutrition. Linear furrows are commonly referred to as linear enamel hypoplasias (LEHs); LEHs can range in size from microscopic to visible to the naked eye. By examining the spacing of perikymata grooves (horizontal growth lines), the duration of the stressor can be estimated, although Mays argued that the width of the hypoplasia bears only an indirect relationship to the duration of the stressor. Studies of dental enamel hypoplasia are used to study child health. Unlike bone, teeth are not remodeled, so intact enamel can provide a more reliable indicator of past health events. Dental hypoplasias provide an indicator of health status during the time in childhood when the enamel of the tooth crown is forming. The presence, frequency, and severity of enamel hypoplasia (EH) offer valuable information about general health conditions and the occurrence of disease or malnutrition. Elevated rates of EH are often interpreted as evidence of widespread physiological stress, such as famine, infectious disease outbreaks, or prolonged nutritional deficiencies. By comparing the prevalence of dental stress indicators across various groups such as different social classes, geographic regions, or time periods bioarcheologists can also infer disparities in living conditions, access to resources, and overall health.
elegans this initiation response is amplified through the synthesis of a population of 'secondary' siRNAs during which the Dicer-produced initiating or 'primary' siRNAs are used as templates. These 'secondary' siRNAs are structurally distinct from Dicer-produced siRNAs and appear to be produced by an RNA-dependent RNA polymerase (RdRP).
=== Dendritic secretion === Supraoptic neurons have typically 1-3 large dendrites, most of which projecting ventrally to form a mat of process at the base of the nucleus, called the ventral glial lamina. The dendrites receive most of the synaptic terminals from afferent neurons that regulate the supraoptic neurons, but neuronal dendrites are often actively involved in information processing, rather than being simply passive receivers of information. The dendrites of supraoptic neurons contain large numbers of neurosecretory vesicles that contain oxytocin and vasopressin, and they can be released from the dendrites by exocytosis. The oxytocin and vasopressin that is released at the posterior pituitary gland enters the blood, and cannot re-enter the brain because the blood–brain barrier does not allow oxytocin and vasopressin through, but the oxytocin and vasopressin that is released from dendrites acts within the brain. Oxytocin neurons themselves express oxytocin receptors, and vasopressin neurons express vasopressin receptors, so dendritically released peptides "autoregulate" the supraoptic neurons. Francoise Moos and Phillipe Richard first showed that the autoregulatory action of oxytocin is important for the milk-ejection reflex. These peptides have relatively long half-lives in the brain (about 20 minutes in the CSF), and they are released in large amounts in the supraoptic nucleus, and so they are available to diffuse through the extracellular spaces of the brain to act at distant targets.
Sources: en.wikipedia.org
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.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
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.