Everything below concerns primary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-10-21. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
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.
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 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.
| 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 low pressure used during drying allows water vapor to move from the ice surface to a cold condenser. Energy supplied as heat drives sublimation but must stay below the collapse temperature of the frozen matrix. If the product becomes too warm, the frozen structure may soften or melt, reducing pore formation and slowing drying. Formulations often include bulking agents, stabilizers, or buffers to support a rigid cake. The final moisture content depends on formulation, freezing rate, and the length of secondary drying.
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.
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.
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.
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.
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.
== Poor usage of Iran's agricultural land == Approximately one-third of Iran's total surface area consists of arable farmland; however, less than one-fourth of this—equivalent to about one-tenth of the total land area—is actively cultivated. This limited cultivation is due to poor soil quality and inadequate water distribution across many regions. Of the cultivated land, less than one-third benefits from irrigation, while most rely on dry farming techniques. The most fertile soils are found in the western and northwestern regions of the country.
On November 27, The Washington Post published an article alleging that Secretary of Defense Pete Hegseth had ordered the officers responsible for the first airstrike on September 2, 2025, to "kill everyone" on board, prompting Admiral Frank M. Bradley to order a second strike to kill the two survivors of the initial strike, who were clinging to the wreckage of the boat that had been by the initial strike. As no quarter orders are forbidden under the Law of war, the second September 2 strike was widely criticized as constituting a war crime even under the Trump Administration's justification for the boat strike campaign in general, with the chair of the United States Senate Committee on Armed Services, Republican Senator Roger Wicker, along with ranking member Jack Reed, promising "vigorous oversight to determine the facts related to these circumstances". According to The New York Times, five U.S. officials stated that while Hegseth did, on September 2, order the killing of all individuals aboard the alleged drug boat, he did not specifically address what was to be done if any individuals survived the initial strike and was not present when Bradley carried out the second strike. After Hegseth refused to release a video of the second strike to Congress, the United States Senate placed a provision in the 2026 National Defense Authorization Act holding back a quarter of Hegseth's travel budget until he showed the video to lawmakers.
=== Malaria vaccine === In 2014, GSK applied for regulatory approval for the first malaria vaccine. Malaria is responsible for over 650,000 deaths annually, mainly in Africa. Known as RTS,S, the vaccine was developed as a joint project with the PATH vaccines initiative and the Bill and Melinda Gates Foundation. The company has committed to making the vaccine available in developing countries for five per cent above the cost of production. As of 2013, RTS,S, which uses GSK's proprietary AS01 adjuvant, was being examined in a Phase 3 trial in eight African countries. PATH reported that "[i]n the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines." In 2014, Glaxo said it had spent more than US$350 million and expected to spend an additional US$260 million before seeking regulatory approval.
== History == The first compact computer controlled robotic arms appeared in the early 1980s, and have continuously been employed in laboratories since then. These robots can be programmed to perform many different tasks, including sample preparation and handling. Yet in the early 1980s, a group led by Masahide Sasaki, from Kochi Medical School, introduced the first fully automated laboratory employing several robotic arms working together with conveyor belts and automated analyzers. The success of Sasaki's pioneer efforts made other groups around the world to adopt the approach of Total Laboratory Automation (TLA). Despite the undeniable success of TLA, its multimillion-dollar cost prevented that most laboratories adopted it. Also, the lack of communication between different devices slowed down the development of automation solutions for different applications, while contributing to keeping costs high. Therefore, the industry attempted several times to develop standards that different vendors would follow in order to enable communication between their devices. However, the success of this approach has been only partial, as nowadays many laboratories still do not employ robots for many tasks due to their high costs. Recently, a different solution for the problem became available, enabling the use of inexpensive devices, including open-source hardware, to perform many different tasks in the laboratory. This solution is the use of scripting languages that can control mouse clicks and keyboard inputs, like AutoIt.
Balbacua, also spelled balbakwa or balbakoa, is a Filipino beef stew made from beef, collagen-rich beef parts (oxtail, skin, and joints), and various spices cooked for several hours until very tender. It is typically served with white rice or misua or miki noodles. It originates from the Visayan regions of the Visayas and Mindanao islands.
Sources: en.wikipedia.org
=== Bulimia nervosa === A 2011 systematic review discussed seven trials that compared fluoxetine to a placebo in the treatment of bulimia nervosa, six of which found a statistically significant reduction in symptoms such as vomiting and binge eating. However, no difference was observed between treatment arms when fluoxetine and psychotherapy were compared to psychotherapy alone.
Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment.[78] They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of glabellar frown lines was published in 1992. This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials. Well before this, the cosmetic use of botulinum toxin type A became widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US Food and Drug Administration (FDA) approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market. Botulinum toxin type-A has also been used in the treatment of gummy smiles; the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of gingiva.
=== Murder cases === 1965: Tan Kheng Ann (alias Robert Black) and 17 others who led the Pulau Senang prison riot. They were found guilty of the murders of a prison officer and his three assistants, and hanged on 29 October 1965. 1968: Usman bin Haji Muhammad Ali and Harun Thohir, two Indonesian marines who carried out the 1965 MacDonald House bombing which killed three people (when Singapore was still a part of Malaysia). They were convicted of murder and hanged on 17 October 1968. 1970: Lim Heng Soon and Low Ngah Ngah, the two Singaporeans found guilty of stabbing and killing police detective D. Munusamy in February 1968. Both men were sentenced to hang on 30 November 1968, and after losing their appeals to the Singaporean Court of Appeal and Privy Council in London between November 1969 and March 1970, the duo were eventually hanged. 1972: Liew Kim Siong and Kee Ah Tee, the two Singaporean youths hanged in 1972 for the 1969 Upper Bukit Timah factory murders, where two Hongkongers were stabbed to death during the duo's robbery bid 1973: Osman bin Ali, an Indonesian-born Singaporean and gardener who was found guilty of murdering a cook and an amah at a bungalow in Leedon Park. He was sentenced to death in September 1971, and hanged on 27 July 1973 after losing his appeal. 1973: Mimi Wong Weng Siu and her husband Sim Woh Kum, the first couple to be sentenced to death in Singapore. Both Wong and Sim were convicted of the 1970 murder of Ayako Watanabe, the wife of Wong's Japanese lover, and hanged on 27 July 1973.
== Other uses == lh (digraph), in many languages Bristol LH, a type of British bus manufactured between 1967 and 1982 Chrysler LH platform, a type of Chrysler car made from 1993 through 2004 Late Helladic, a period in the history of ancient Greece, during the Bronze Age Leasehold, or tenure, in property law Left-handed, or left hand Letterhead, a heading at the top of a sheet of letter paper Lewis Hamilton (born 1985), British racing driver
Sources: en.wikipedia.org
=== Pharmacokinetics === It is possible that MDDMA could be partially demethylated into MDMA. However, based on (R)-MDDMA and (R)-MDMA having very different effects in animals, such conversion appears to be limited.
October 20 – The district attorney of Westchester County announces a criminal investigation into The Trump Organization. October 21 – Rust shooting incident: Film producer Alec Baldwin fatally shoots Halyna Hutchins and wounds Joel Souza during the filming of Rust, when a prop firearm is discharged by accident. October 22 – Trump–Ukraine scandal: Former Rudy Giuliani associate Lev Parnas is convicted by the SDNY for campaign financing crimes and for illegally funding foreign cash to Republicans during the 2018 midterms. The conviction is announced by Attorney Damian Williams. October 23 – 2021 NCAA Division I FBS football season: In college football, the Illinois Fighting Illini defeats Penn State 20-18 in nine overtimes, making it the longest football game played in NCAA history. October 26 – A report comes out revealing that former Chicago Blackhawks coach Brad Aldrich sexually assaulted Kyle Beach, a young prospect on the team during the 2009–10 NHL season. The report also shows that Stan Bowman, Kevin Cheveldayoff, and Joel Quenneville met before the 2010 Stanley Cup Finals and allowed Aldrich to continue working until the end of the season. October 28 – Mark Zuckerberg announces that Facebook, Inc., owner of Facebook, Instagram, WhatsApp and Oculus, will rebrand itself as Meta Platforms. October 29 MrBeast and Mark Rober launch #TeamSeas, a project to clean up 30 million pounds of ocean trash by the end of the year. The U.S. Food and Drug Administration authorizes the emergency use of the Pfizer-BioNTech COVID-19 vaccine for children 5 through 11 years of age.
Affinity chromatography is based on selective non-covalent interaction between an analyte and specific molecules. It is very specific, but not very robust. It is often used in biochemistry in the purification of proteins bound to tags. These fusion proteins are labeled with compounds such as His-tags, biotin or antigens, which bind to the stationary phase specifically. After purification, these tags are usually removed and the pure protein is obtained. Affinity chromatography often utilizes a biomolecule's affinity for the cations of a metal (Zn, Cu, Fe, etc.). Columns are often manually prepared and could be designed specifically for the proteins of interest. Traditional affinity columns are used as a preparative step to flush out unwanted biomolecules, or as a primary step in analyzing a protein with unknown physical properties. However, liquid chromatography techniques exist that do utilize affinity chromatography properties. Immobilized metal affinity chromatography (IMAC) is useful to separate the aforementioned molecules based on the relative affinity for the metal. Often these columns can be loaded with different metals to create a column with a targeted affinity.
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.
Simple drying usually removes water by evaporation from a liquid or solid, often with heat. Lyophilization first freezes the material and then removes ice by sublimation under vacuum. This avoids prolonged exposure to liquid water and high temperatures.