A practical reference on Lyophilization: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-09-28 and is reviewed periodically as new material appears.
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.
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.
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.
| 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. |
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.
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.
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.
=== Fa–Fi === Kazimierz Fajans (1887–1975), Polish-American physical chemist, who worked on radioactivity and co-discovered protactinium Michael Faraday (1791–1867), British chemist and physicist who discovered include the principles of electromagnetic induction, diamagnetism, and electrolysis Hermann von Fehling (1812–1885), German chemist who developed use of Fehling's solution for estimation of sugar John Bennett Fenn (1917–2010), 2002 Nobel Prize in Chemistry for work in mass spectrometry Enrico Fermi (1901–1954), Nuclear chemist and elementary particle physicist, Nobel Prize in Physics 1938 Louis Fieser (1899–1977), American chemist who work on blood-clotting agents including the first synthesis of vitamin K, and was the author of numerous textbooks Mary Peters Fieser (1909–1997), American chemist who worked on quinones and steroids, and was co-author of chemistry books Barbara J. Finlayson-Pitts (PhD 1973), Canadian-American chemist who works on the chemistry of the upper and lower atmosphere Emil Fischer (1852–1919), 1902 Nobel Prize in Chemistry, known for work on stereochemistry and for the lock and key mechanism of enzyme action Emily V.
== Interactions == No interaction studies with this substance have been performed. Interactions with systemic (for example, oral) drugs are considered unlikely because bimatoprost does not reach relevant concentrations in the bloodstream. Bimatoprost does not negatively interact with timolol eye drops.
In 2012, Professor Paolo Macchiarini and his team improved upon the 2008 implant by transplanting a laboratory-made trachea seeded with the patient's own cells. On September 12, 2014, surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe, Japan, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells, which were differentiated from iPS cells through directed differentiation, into an eye of an elderly woman, who suffers from age-related macular degeneration. In 2016, Paolo Macchiarini was fired from Karolinska University in Sweden due to falsified test results and lies. The TV-show Experimenten aired on Swedish Television and detailed all the lies and falsified results.
This means that, on average, its papers published in 2015 and 2016 received roughly 42 citations each in 2017. Impact factors are reported in the subsequent year, when all of the previous year's publications have been processed by the indexing agency. The value of impact factor depends on how to define "citations" and "publications"; the latter are often referred to as "citable items". In current practice, both "citations" and "publications" are defined exclusively by ISI as follows: "Publications" are items that are classed as "article", "review" or "proceedings paper" in the Web of Science (WoS) database; other items like editorials, corrections, notes, retractions and discussions are excluded. WoS is accessible to all registered users, who can independently verify the number of citable items for a given journal. In contrast, the number of citations is extracted not from the WoS database, but from a dedicated JCR database, which is not accessible to general readers. Hence, the commonly used "JCR Impact Factor" is a proprietary value, which is defined and calculated by ISI and can not be verified by external users. New journals, which are indexed from their first published issue, will receive an impact factor after two years of indexing; in this case, the citations to the year prior to volume 1, and the number of articles published in the year prior to volume 1, are known zero values. Journals that are indexed starting with a volume other than the first volume will not get an impact factor until they have been indexed for three years.
Sources: en.wikipedia.org
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.
== Reactivity == Like most alkanes, hexanes typically exhibit low reactivity and are suitable solvents for reactive compounds. Commercial samples of n-hexane however often contains methylcyclopentane, which features tertiary C-H bonds, which are incompatible with some radical reactions.
== Medical uses == Levothyroxine is typically used to treat hypothyroidism, and is the treatment of choice for people with hypothyroidism who often require lifelong thyroid hormone therapy. It may also be used to treat goiter via its ability to lower thyroid-stimulating hormone (TSH), which is considered goiter-inducing. Levothyroxine is also used as interventional therapy in people with nodular thyroid disease or thyroid cancer to suppress TSH secretion. A subset of people with hypothyroidism treated with an appropriate dose of levothyroxine will describe continuing symptoms despite TSH levels in the normal range. In these people, further laboratory and clinical evaluation is warranted, as they may have another cause for their symptoms. Furthermore, reviewing their medications and dietary supplements is important, as several medications can affect thyroid hormone levels. Levothyroxine is also used to treat subclinical hypothyroidism, which is defined by an elevated TSH level and a normal-range free T4 level without symptoms. Such people may be asymptomatic and whether they should be treated is controversial. One benefit of treating this population with levothyroxine therapy is preventing the development of hypothyroidism. As such, treatment should be taken into account for patients with initial TSH levels above 10 mIU/L, people with elevated thyroid peroxidase antibody titers, people with symptoms of hypothyroidism and TSH levels of 5–10 mIU/L, and women who are pregnant or want to become pregnant. Oral dosing for patients with subclinical hypothyroidism is 1 μg/kg/day.
=== Views on homosexuality === Jung addressed homosexuality in his published writings, in one comment specifying that homosexuality should not be a concern of legal authorities nor be considered a crime. He also stated that homosexuality does not reduce the value of a person as a member of society. Jung also said that homosexuality is a result of psychological immaturity ("nurture"), but only if one's sexuality is not an aspect of their constitutional characteristics ("nature").
Chloroplasts, like other endosymbiotic organelles, contain a genome separate from that in the cell nucleus. The existence of chloroplast DNA (cpDNA) was identified biochemically in 1959, and confirmed by electron microscopy in 1962. The discoveries that the chloroplast contains ribosomes and performs protein synthesis revealed that the chloroplast is genetically semi-autonomous. Chloroplast DNA was first sequenced in 1986. Since then, hundreds of chloroplast genomes from various species have been sequenced, but they are mostly those of land plants and green algae—glaucophytes, red algae, and other algal groups are extremely underrepresented, potentially introducing some bias in views of "typical" chloroplast DNA structure and content.
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.
Yes. Lyophilization and freeze-drying are synonyms for the same vacuum-assisted sublimation process. The term lyophilization is more common in pharmaceutical and laboratory settings, while freeze-drying is widely used in food and general contexts.