If you have been reading about Karl Fischer titration and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-06-28. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
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.
Quality control for lyophilized materials includes visual inspection of the cake, measurement of residual moisture, and tests for reconstitution time. An acceptable cake is typically uniform and may be slightly porous; shrinkage, meltback, or cracks can indicate process deviations. Analytical methods such as Karl Fischer titration, thermogravimetric analysis, and near-infrared spectroscopy quantify water content. Reconstitution time is recorded because a very slow or incomplete dissolution can signal collapse or aggregation. Stability studies compare samples stored under defined temperature and humidity conditions over months or years.
Regulatory expectations for lyophilized products focus on consistent manufacture and documented stability. Batches are often monitored for moisture, appearance, potency, and sterility where applicable. Process parameters such as shelf temperature, chamber pressure, and drying time are recorded and controlled within validated ranges. Open questions remain about how best to predict long-term stability from short accelerated studies, especially for complex biologics. Variations in freezing rate and ice crystal size can produce differences that are not always visible but may affect performance.
After drying, a lyophilized product is usually sealed under vacuum or an inert gas to limit moisture uptake. Residual water content is measured because small changes can alter chemical stability and cake appearance. Storage temperature depends on the material; many biological products are kept at 2–8 °C, while some require −20 °C or colder. Exposure to ambient humidity during handling can cause the porous solid to absorb water and collapse. Container closures and stoppers are therefore selected for low moisture transmission and compatibility.
| Property | Value | Notes |
|---|---|---|
| Process name | Lyophilization or freeze-drying | Both terms appear in technical standards and literature. |
| Phase transition | Sublimation | Solid ice becomes vapor without a liquid step. |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product temperature and equipment. |
| Typical product temperature | -40 °C to -10 °C | Measured during primary drying; formulation sets limits. |
| Water content after drying | 0.5-3% w/w | Target varies by material and stability needs. |
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.
Lyophilization, also called freeze-drying, is a dehydration process in which a solvent, usually water, is frozen and then removed by sublimation under reduced pressure. The method preserves heat-sensitive materials that would degrade in conventional drying. Large-scale use grew during the mid-twentieth century for blood plasma and antibiotics, and it later expanded to vaccines, enzymes, foods, and advanced materials. The process produces a dry, porous solid that usually reconstitutes rapidly. It is distinct from simple evaporation because the solvent bypasses the liquid phase during primary removal.
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.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
Lyophilized products are typically stored as sealed solids in vials or syringes. Moisture ingress is a major concern because many dried cakes are hygroscopic and can lose stability when exposed to humid air. Storage temperature depends on the formulation; some products are kept refrigerated, while others are stable at room temperature. Container closure integrity and headspace moisture are often monitored. Light protection may also be required for some photosensitive materials.
May 2016 – MacMillan Films released a full staging of the original Medea which was staged for camera. The DVD release shows the entire play. complete with the Aegis scenes, choral odes and triumphant ending. Directed by James Thomas and starring Olivia Sutherland, the staging features Peter Arnott's critically acclaimed translation. Chico Buarque and Paulo Pontes, Gota d'Água (musical play set in 1970s Rio de Janeiro, based on Euripides, 1975). Several times revived, including a 2016/2017 production starring Laila Garin (celebrated for her title role in the highly regarded musical biography of Elis Regina, staged in Brasil in 2015). February 2017: the play was staged in South Korea, directed by Hungarian theatre director Róbert Alföldi, with Lee Hye-young in the titular role.
Personal website Sweeney, Brigid (2011). "Crain's 40 Under 40". Chicago Business. Mitroff, Sarah (October 17, 2012). "Braintree Seeks Online Payment Domination". Wired. Bryan Johnson's channel on YouTube
Biopharmaceuticals may be produced from microbial cells (e.g., recombinant E. coli or yeast cultures), mammalian cell lines (see Cell culture) and plant cell cultures (see Plant tissue culture) and moss plants in bioreactors of various configurations, including photo-bioreactors. Important issues of concern are cost of production (low-volume, high-purity products are desirable) and microbial contamination (by bacteria, viruses, mycoplasma). Alternative platforms of production which are being tested include whole plants (plant-made pharmaceuticals).
Soy-based food products, such as soybeans, miso, tempeh, tofu, meatless soy burgers, and soy protein infant foods contain the highest amounts of isoflavones. According to a 2006 study of nine common phytoestrogens in Canadian foods, the highest relative phytoestrogen content were nuts and oilseeds, followed by soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. The highest concentrations of isoflavones are found in soybeans and soybean products followed by legumes, whereas lignans are the primary source of phytoestrogens found in nuts and oilseeds (e.g. flax) and also found in cereals, legumes, fruits and vegetables. Phytoestrogen content varies in different foods, and may vary significantly within the same group of foods (e.g. soy beverages, tofu) depending on processing mechanisms and type of soybean used. Legumes (in particular soybeans), whole grain cereals, and some seeds are high in phytoestrogens. Food content of phytoestrogens is highly variable, and accurate estimates of intake are therefore difficult and depends on the databases used. Data from the European Prospective Investigation into Cancer and Nutrition found intakes between 1 mg/d in Mediterranean Countries and more than 20 mg/d in the United Kingdom.
Sources: en.wikipedia.org
In 1963, promethium(III) fluoride was used to make promethium metal. Provisionally purified from impurities of samarium, neodymium, and americium, it was put into a tantalum crucible which was located in another tantalum crucible; the outer crucible contained lithium metal (10 times excess compared to promethium). After creating a vacuum, the chemicals were mixed to produce promethium metal:
Ridomihan Kersus (リドミハ星人カーサス, Ridomiha Seijin Kāsasu): A plant-themed criminal from Planet Ridomiha who is charged with murder and planetary invasion and is capable of secreting healing liquid from her stalks and producing high-powered water streams capable of slicing objects. Due to their homeworld changing from a water-based planet to a desert-based one, she and her sister Karmia (カーミア, Kāmia) scouted Earth with the intention of stealing its water. After Karmia developed second thoughts, Kersus killed her and framed an alien named Braidy, but Sen-Chan discovers the truth before the Dekarangers delete Kersus with the D-Bazooka. Kersus is voiced by Tomoka Hayashi (林 知花, Hayashi Tomoka), who also portrays her human form. Cuwartlian Dazgonelr (クウォータ星人ダゴネール, Kuwōta Seijin Dagonēru): A childish 10,708-year-old octopus-themed Alienizer from Planet Cuwartl who is charged with turning people into dolls. He manipulates Hikaru, a lonely boy with the power to teleport objects, into helping him before he is deleted by Dekaranger Robo while piloting the Kaijuki Embarns (エンバーンズ, Enbānzu). Dazgonelr is voiced by Yasuhiro Takato (高戸 靖広, Takato Yasuhiro). Zamuzan Sheik (ザムザ星人シェイク, Zamuza Seijin Sheiku): A beetle-themed criminal and bomb manufacturer from Planet Zamuza who was arrested on charges of mass-murder via explosives and imprisoned in the Prison Satellite Prisron (監獄衛生プリズロン, Kangoku Eisei Purizuron).
TikTok was downloaded over 104 million times on Apple's App Store during the first half of 2018, according to data provided to CNBC by Sensor Tower. After merging with musical.ly in August, downloads increased and TikTok subsequently became the most downloaded app in the US in October 2018, which musical.ly had done once before. In February 2019, TikTok, together with Douyin, hit one billion downloads globally, excluding Android installs in China. In 2019, media outlets cited TikTok as the 7th-most-downloaded mobile app of the decade, from 2010 to 2019. It was also the most-downloaded app on Apple's App Store in 2018 and 2019, surpassing Facebook, YouTube and Instagram. In September 2020, a deal was confirmed between ByteDance and Oracle in which the latter will serve as a partner to provide cloud hosting. In November 2020, TikTok signed a licensing deal with Sony Music. In December 2020, Warner Music Group signed a licensing deal with TikTok. The advertising revenue of short video clips is lower than other social media: while users spend more time, American audience is monetized at a rate of $0.31 per hour, a third the rate of Facebook and a fifth the rate of Instagram, $67 per year while Instagram will make more than $200. In July 2023, Iranian Mehr News Agency reported "experts from Douyin" will meet Iranian business in Tehran to enable Iranian exports to China. In 2023, several high-level executives transferred from ByteDance to TikTok to focus on moneymaking operations. Some moved from Beijing to the US.
=== Category:EC 1.13 (act on single donors with incorporation of molecular oxygen) === Category:EC 1.13.11 (With incorporation of two atoms of oxygen) 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) Category:EC 1.13.12 (With incorporation of one atom of oxygen (internal monooxygenases or internal mixed function oxidases)) Renilla-luciferin 2-monooxygenase EC 1.13.12.5 Cypridina-luciferin 2-monooxygenase EC 1.13.12.6 Firefly luciferase EC 1.13.12.7 Watasenia-luciferin 2-monooxygenase EC 1.13.12.8 Oplophorus-luciferin 2-monooxygenase EC 1.13.12.13
Certain mutations in rRNA that were able to trigger rRNA degradation in eukaryotes were unable to do so in prokaryotes. Point mutations in a 23S rRNA would cause both 23S and 16S rRNAs to be degraded, in comparison to eukaryotes, in which mutations in one subunit would only cause that subunit to be degraded. Researchers found that removal of a whole helix structure (H69) from the 23S rRNA did not trigger its degradation. This led them to believe that H69 was critical for endonucleases to recognize and degrade the mutated rRNA.
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.
Lowering pressure reduces the boiling point of water and allows ice to sublimate at temperatures below freezing. Vacuum also limits convective heat transfer, so heat is usually supplied by shelves or radiation. The pressure must stay below the vapor pressure of ice at the product temperature.
The cycle typically includes freezing, primary drying, and secondary drying. Freezing solidifies water and sets the pore structure; primary drying removes bulk ice; secondary drying removes bound water. Some cycles add annealing or pre-freezing steps.
Most are held in sealed containers at controlled temperatures, often 2–8 °C, while some require frozen storage. Protection from moisture and light helps preserve the dry matrix. Exact conditions are set by the manufacturer or study protocol.