This is a working overview of secondary drying, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-19. Anything still debated is marked as such rather than presented as settled.
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.
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.
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 names | Lyophilization; freeze-drying | Terms used interchangeably. |
| Phase change | Sublimation | Ice converts directly to vapor under vacuum. |
| Typical chamber pressure | 0.01–1 mbar | Below the triple point of water. |
| Primary drying product temperature | −40 to −10 °C | Kept below collapse or glass transition temperature. |
| Water content after drying | 0.5–3% w/w | Varies with formulation and cycle. |
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.
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.
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.
=== Merger with Carl's Jr. and aftermath === In April 1997, CKE Restaurants Holdings, Inc., the parent company of Carl's Jr., bought Hardee's from Imasco for $327 million. The merger created a chain of 3,828 restaurants – 3,152 Hardee's outlets in 40 states and 10 foreign countries and 676 Carl's Jr. outlets primarily in California. Initially, the plan was for the larger Hardee's chain to completely rebrand as Carl's Jr but continue to offer Hardee's existing breakfast menu branded as "Hardee's breakfast" (due to Hardee's stronger sales during breakfast hours, unusual among fast food chains), and even ran a test by rebranding Hardee's locations in the Peoria, Illinois and Oklahoma City, Oklahoma markets as Carl's Jr. However, by 1999 CKE instead rebranded Hardee's into the Carl's Jr. imaging including the Happy Star logo and parts of its lunch menu but kept the Hardee's name and left the breakfast menu intact, though the Oklahoma City locations kept the Carl's Jr. branding permanently. In 1998, Hardee's acquired 557 of the franchised restaurants from Advantica Restaurant Group. In 2001, Hardee's headquarters moved to St. Louis, Missouri. In 2005, Hardee's introduced Hand-Scooped Ice Cream Shakes & Malts. In 2007, CKE Restaurants sold 34 Hardee's locations in North Carolina to longtime franchisee Boddie-Noell Enterprises. In 2008, CKE Restaurants sold 23 Hardee's restaurants in Indiana and Ohio to Midwest First Star, and nine in Davenport, Iowa to Westar Foods. In September 2013, it was announced that Hardee's would expand into the Northeastern United States.
When they had opened his tomb and they thought his body would stink because of the amount of time that had elapsed since it had been buried, such a sweet fragrant odor like a diversity of flowers flowed forth, and the whole church was filled with little drops of balsam. And when the brothers who had come to see him from the neighboring province... removed the clothes in which he had been buried because they wanted to change them wishing to dress him in new clothes, they found on his forearms the sign of the dominical cross, bearing the likeness of a red color. It was evident to all the faithful that this was given to be understood that while he lived he bore the arms of Christ in his heart, therefore, Christ's stigmata were revealed on the body of the dead man.
In electron capture, some proton-rich nuclides were found to capture their own atomic electrons instead of emitting positrons, and subsequently, these nuclides emit only a neutrino and a gamma ray from the excited nucleus (and often also Auger electrons and characteristic X-rays, as a result of the re-ordering of electrons to fill the place of the missing captured electron). These types of decay involve the nuclear capture of electrons or emission of electrons or positrons, and thus acts to move a nucleus toward the ratio of neutrons to protons that has the least energy for a given total number of nucleons. This consequently produces a more stable (lower energy) nucleus. A hypothetical process of positron capture, analogous to electron capture, is theoretically possible in antimatter atoms, but has not been observed, as complex antimatter atoms beyond antihelium are not experimentally available. Such a decay would require antimatter atoms at least as complex as beryllium-7, which is the lightest known isotope of normal matter to undergo decay by electron capture.
Main reactor Ethylene oxide scrubber Ethylene oxide de-sorber Stripping and distillation column CO2 scrubber and CO2 de-scrubber Main Reactor: The main reactor consists of thousands of catalyst tubes in bundles. These tubes are generally 6 to 15 m (20 to 50 ft) long with an inner diameter of 20 to 50 mm (0.8 to 2.0 in). The catalyst packed in these tubes is in the form of spheres or rings of diameter 3 to 10 mm (0.12 to 0.39 in). The operating conditions of 200–300 °C (390–570 °F) with a pressure of 1–3 MPa (150–440 psi) prevail in the reactor. To maintain this temperature, the cooling system of the reactor plays a vital role. With the aging of the catalyst, its selectivity decreases and it produces more exothermic side products of CO2. Ethylene oxide scrubber: After the gaseous stream from the main reactor, containing ethylene oxide (1–2%) and CO2 (5%), is cooled, it is then passed to the ethylene oxide scrubber. Here, water is used as the scrubbing media which scrubs away majority of ethylene oxide along with some amounts of CO2, N2, CH2=CH2, CH4 and aldehydes (introduced by the recycle stream). Also, a small proportion of the gas leaving the ethylene oxide scrubber (0.1–0.2%) is removed continuously (combusted) to prevent the buildup of inert compounds (N2, Ar, and C2H6), which are introduced as impurities with the reactants. Ethylene oxide de-sorber: The aqueous stream resulting from the above scrubbing process is then sent to the ethylene oxide de-sorber.
Sources: en.wikipedia.org
The Boer War saw the first war crimes prosecutions in British history. They centered around the Bushveldt Carbineers (BVC), a British Army irregular regiment of mounted rifles active in the Northern Transvaal. Originally raised in February 1901, the BVC was composed of British and Commonwealth servicemen with an admixture of defectors from the Boer Commandos. On 4 October 1901, a letter signed by 15 members of the Bushveldt Carbineers (BVC) garrison at Fort Edward was secretly dispatched to Col. F.H. Hall, the British Army Officer Commanding at Pietersburg. Written by BVC Trooper Robert Mitchell Cochrane, a former justice of the peace from Western Australia, the letter accused members of the Fort Edward garrison of six "disgraceful incidents":
== Development == The first implementation of this technique is attributed to J. J. Kirkland and R. K. Iler of DuPont, who carried it out using microparticles in 1966. The method was later revitalized by the discovery of its applicability to a wide range of polyelectrolytes by Gero Decher at the University of Mainz, with Decher, Helmuth Möhwald, and Yuri Lvov credited for developing LbL assembly for multicomponent films made up of polyions (such as DNA, RNA, and proteins), as well as other charged materials. Nicholas Kotov pioneered the development of biomimetic and high-performance composites through the LbL assembly of nanomaterials such as graphene oxide nanoplatelets.
– the particles are not coated or surface modified. In July 2025, the Scientific Committee on Consumer Safety (SCCS) adopted its fourth opinion (Submission IV), concluding that nano‑hydroxyapatite is safe at concentrations up to 29.5% in toothpaste and up to 10% in mouthwash, under defined particle morphology constraints.
==== Class A sub-family ==== Class A enzymes methylate specific adenosine residues on rRNA and/or tRNA. In other words, they are RNA base-modifying radical SAM enzymes. The most mechanistically well-characterized are enzymes RlmN and Cfr. Both enzymes methylates substrate by adding a methylene fragment originating from SAM molecule. Therefore, RlmN and Cfr are considered methyl synthases instead of methyltransferases.
=== Reception === The Bush presidency has been ranked as below-average in surveys of presidential scholars published in the late 2000s and 2010s. A 2010 Siena Research Institute survey of the opinions of historians, political scientists, and presidential scholars ranked him 39th out of 43 presidents. The survey respondents gave Bush low ratings on his handling of the economy, communication, ability to compromise, foreign policy, and intelligence. Bush said in 2013, "Ultimately history will judge the decisions I made, and I won't be around because it will take time for the objective historians to show up. So I am pretty comfortable with it. I did what I did." C-SPAN's 2021 survey of historians ranked Bush as the 29th-best president; Bush had initially been ranked 36th in 2009. Among the public, his reputation has improved in the U.S. since his presidency ended in 2009. In 2012, Gallup reported that "Americans still rate George W. Bush among the worst presidents, though their views have become more positive in the three years since he left office." A poll conducted in 2013 marked the first time recorded by Gallup that his ratings were more positive than negative, with 49 percent viewing him favorably compared to 46 percent unfavorably. Other pollsters have noted similar trends of slight improvement in Bush's personal favorability since the end of his presidency. In April 2013, Bush's approval rating stood at 47 percent approval and 50 percent disapproval in a poll jointly conducted for The Washington Post and ABC, his highest approval rating since December 2005.
Sources: en.wikipedia.org
Although considered plausible, Wu's hypothesis was not immediately accepted, since so little was known of protein structure and enzymology and other factors could account for the changes in solubility, enzymatic activity and chemical reactivity. In the early 1960s, Chris Anfinsen showed that the folding of ribonuclease A was fully reversible with no external cofactors needed, verifying the "thermodynamic hypothesis" of protein folding that the folded state represents the global minimum of free energy for the protein. The hypothesis of protein folding was followed by research into the physical interactions that stabilize folded protein structures. The crucial role of hydrophobic interactions was hypothesized by Dorothy Wrinch and Irving Langmuir, as a mechanism that might stabilize her cyclol structures. Although supported by J. D. Bernal and others, this (correct) hypothesis was rejected along with the cyclol hypothesis, which was disproven in the 1930s by Linus Pauling (among others). Instead, Pauling championed the idea that protein structure was stabilized mainly by hydrogen bonds, an idea advanced initially by William Astbury (1933). Remarkably, Pauling's incorrect theory about H-bonds resulted in his correct models for the secondary structure elements of proteins, the alpha helix and the beta sheet. The hydrophobic interaction was restored to its correct prominence by a famous article in 1959 by Walter Kauzmann on denaturation, based partly on work by Kaj Linderstrøm-Lang.
It is used to determine insulin dose adjustments, determine lowest and highest blood glucose levels, discover insulin duration and, in the case of continued hyperglycemia, whether the cause is insufficient insulin dose or Somogyi rebound, where blood glucose levels initially reach hypoglycemic levels and are brought to hyperglycemic ones by the body's counterregulatory hormones. Curves also provide evidence of insulin resistance which may be caused by medications other than insulin or by disorders other than diabetes which further testing can help identify. Other diagnostic tests to determine the level of diabetic control are fructosamine and glycated hemoglobin (GHb) blood tests which can be useful especially if stress may be a factor. While anxiety or stress may influence the results of blood or urine glucose tests, both of these tests measure glycated proteins, which are not affected by them. Fructosamine testing provides information about blood glucose control for an approximate 2- to 4-week period, while GHb tests measure a 2- to 4-month period. Each of these tests has its own limitations and drawbacks and neither are intended to be replacements for blood glucose testing and curves, but are to be used to supplement the information gained from them. While HbA1c tests are a common diagnostic for diabetes in humans, only recently has an A1C test become available for cats and dogs. The product is called A1CARE and is available from Baycom Diagnostics.
=== Haemophilus influenzae type b (Hib) infection === Naturally acquired disease caused by H. influenzae seems to occur in humans only. In healthy children under the age of 5, H. influenzae type b was responsible for more than 80% of aggressive infections, before the introduction of the [Hib] vaccine. In infants and young children, H. influenzae type b (Hib) causes bacteremia, pneumonia, epiglottitis and acute bacterial meningitis. On occasion, it causes cellulitis, osteomyelitis, and infectious arthritis. It is one cause of neonatal infection. Due to routine use of the Hib vaccine in the US since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 in children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where the vaccine is not widely used. Unencapsulated H. influenzae strains are unaffected by the Hib vaccine and cause ear infections (otitis media), eye infections (conjunctivitis), and sinusitis in children, and are associated with pneumonia.
== Adverse reactions == The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves), but this may reflect the very high doses given, which are much higher than the doses currently recommended by any manufacturer and for which no adjustment was made for pre-existing renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose. At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen. Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and it has been used for extended periods up to six months with no ill effects. Colistin-induced nephrotoxicity is particularly likely in patients with hypoalbuminemia. The main toxicity described with aerosolised treatment is bronchospasm, which can be treated or prevented with the use of β2-adrenergic receptor agonists such as salbutamol or following a desensitisation protocol.
Vericrustacea ("true crustaceans")—Branchiopoda, Copepoda, Malacostraca, Thecostraca. Multicrustacea ("numerous crustaceans")—Copepoda, Malacostraca, Thecostraca. Communostraca ("common shelled ones")—Malacostraca, Thecostraca. Miracrustacea ("surprising crustaceans")—Cephalocarida, Remipedia, Hexapoda. Xenocarida ("strange shrimp")—Cephalocarida, Remipedia. Of these proposed clades, only Multicrustacea was confirmed in later molecular studies.
Sources: en.wikipedia.org
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.
Reduced pressure lowers the boiling point of water and allows ice to sublime below its triple point. Without sufficient vacuum, melting or boiling may occur instead of sublimation, which can damage the product structure.
Heat and mass transfer limit drying once the ice front recedes. The dried layer insulates the frozen core and resists vapor flow, so increasing shelf temperature too quickly can cause collapse or meltback.
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.