Primary drying raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
Reviewed 2025-12-01. Anything still debated is marked as such rather than presented as settled.
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.
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.
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 |
|---|---|---|
| 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. |
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.
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.
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.
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.
Historically, the first parameter for the determination of fracture toughness in the elasto-plastic region was the crack tip opening displacement (CTOD) or "opening at the apex of the crack" indicated. This parameter was determined by Wells during the studies of structural steels, which due to the high toughness could not be characterized with the linear elastic fracture mechanics model. He noted that, before the fracture happened, the walls of the crack were leaving and that the crack tip, after fracture, ranged from acute to rounded off due to plastic deformation. In addition, the rounding of the crack tip was more pronounced in steels with superior toughness. There are a number of alternative definitions of CTOD. In the two most common definitions, CTOD is the displacement at the original crack tip and the 90 degree intercept. The latter definition was suggested by Rice and is commonly used to infer CTOD in finite element models of such. Note that these two definitions are equivalent if the crack tip blunts in a semicircle. Most laboratory measurements of CTOD have been made on edge-cracked specimens loaded in three-point bending. Early experiments used a flat paddle-shaped gage that was inserted into the crack; as the crack opened, the paddle gage rotated, and an electronic signal was sent to an x-y plotter. This method was inaccurate, however, because it was difficult to reach the crack tip with the paddle gage.
The person's medical history; early chronic pain, a childhood history of pain, an emergence of broad pain following physical or psychosocial stress, a general hypersensitivity to touch, smell, noise, taste, hypervigilance, and various somatic symptoms (gastrointestinal, urology, gynecology, neurology) may signal FM. A physical examination and laboratory investigations may be used to eliminate alternative causes. Common tests that are conducted include complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, and thyroid function test. Possible misdiagnoses are
Pumps further up the thin ascending limb, pump out from 400 mOsm into liquid at 600 mOsm, so again the difference is retained at 200 mOsm from the inside to the outside, while the concentration both inside and outside are gradually decreasing as the liquid flow advances. The liquid finally reaches a low concentration of 100 mOsm when leaving the thin ascending limb and passing through the thick one Distal convoluted tubule: Once leaving the loop of Henle the thick ascending limb can optionally reabsorb and re increase the concentration in the nephrons. Collecting duct: The collecting duct receives liquid between 100 mOsm if no re-absorption is done, to 300 or above if re-absorption was used. The collecting duct may continue raising the concentration if required, by gradually pumping out the same ions as the Distal convoluted tubule, using the same gradient as the ascending limbs in the loop of Henle, and reaching the same concentration. Ureter: The liquid urine leaves to the ureter. Same principle is used in hemodialysis within artificial kidney machines.
== Playwrights, screenwriters, producers, and directors == Henry Churchill de Mille (1875), playwright and Georgist; father of film pioneers Cecil B. DeMille and William C. deMille William C. deMille (1900), screenwriter, director, playwright; second president of the Academy of Motion Picture Arts and Sciences; co-founder of the USC School of Cinematic Arts Edgar Allan Woolf (1901), screenwriter, The Wizard of Oz George Middleton (1902), playwright and president of the Dramatists Guild of America Herman Mankiewicz (1917), drama critic for The New Yorker and co-winner of the Academy Award for Best Original Screenplay for Citizen Kane Morrie Ryskind* (1917), winner of the Pulitzer Prize for Drama with George S. Kaufman for Of Thee I Sing and co-writer of The Cocoanuts, Animal Crackers, and A Night at the Opera Sam Spewack (1919), winner of the Tony Award for the book of Kiss Me, Kate Sidney Buchman (1923), screenwriter for Mr. Smith Goes to Washington and winner of the Academy Award for Writing Adapted Screenplay for Here Comes Mr. Jordan Guy Endore (1923), screenwriter for The Story of G.I. Joe Alvah Bessie (1924), screenwriter for Objective, Burma! and one of the Hollywood Ten Ferrin Fraser (1927), radio scriptwriter for Little Orphan Annie and Frank Buck Joseph Mankiewicz (1928), Academy Award-winning writer and director of All About Eve and A Letter to Three Wives Frank S. Nugent (1929), screenwriter for Fort Apache, She Wore a Yellow Ribbon, and The Quiet Man Robert F.
Pressure ulcer – Also known as decubitus ulcers or bedsores, this type of wound is a result of chronic pressure to the skin over a prolonged period. While most individuals have intact sensation and motor function which allow for frequent positional change to prevent the formation of such ulcers, older individuals are particularly susceptible to this type of chronic injury due to impaired neurosensory responses. Pressure ulcers can occur in as little as two hours of immobility in a bedridden patient or person who is otherwise unconscious/sedated (surgery, syncope, etc.). In the United States, pressure ulcers are graded using the National Pressure Injury Advisory Panel (NPIAP) system. In this system, ulcers are graded on wound depth with stage 1 being the least severe (erythema, intact skin) and stage 4 being full thickness damage through subcutaneous tissue down to muscle, tendon, or bone. Any ulcer that cannot be assessed due to overlying eschar is considered unstageable.
Sources: en.wikipedia.org
== Legal status == DNP is banned for human consumption in many countries. Because it has some legitimate uses, in many jurisdictions, DNP is legal to sell, but not for human consumption. DNP has been banned by the World Anti-Doping Association since 2015. Petróczi et al. recommend against campaigns informing people of the risks of DNP because it could increase use of the drug. However, Sousa et al. argue that publicity campaigns in the United Kingdom in the early and mid-2010s reduced DNP usage. In 2015, Interpol and the World Anti-Doping Agency released an orange notice warning of the dangers of DNP. In 1941, the Eastman Kodak Company, a bulk distributor of DNP, was investigated after some of its product was found in illegal diet pills. Nicholas Bachynsky, a Texas physician, provided the drug to patients under the name "Mitcal". He was convicted of violating drug laws in 1986, but continued to work with DNP and was additionally convicted of fraud in 2008. In 2018, a seller in the United Kingdom was convicted of manslaughter for selling DNP for human consumption. The conviction was sent to retrial in 2020 by the English Court of Appeal, where the seller was, once again, convicted of gross negligence manslaughter. The UK government reclassified DNP as a regulated poison with effect from October 2023.
== History == Prior to the UGR's implementation, the U.S. military had several different types of rations used to feed service members in the rear or out of combat. Among them were the A-ration, consisting of fresh, refrigerated, or frozen food prepared in a kitchen and served in a mess, dining facility, or elsewhere; the B-ration, consisting of packaged, preserved foods prepared in a field kitchen; and the T-ration, a semi-perishable meal packaged, heated, and served in a tray pack similar to frozen meals; among others. This created issues for military cooks, who "had to order an average of 34 separate items for each meal, and could only hope that they arrived when needed", forcing them to manage logistics and administrative functions instead of solely food preparation. Around 1995, the U.S. military launched a modernization program to resolve this issue while also increasing the quality and decreasing the cost of existing rations. Research was headed by the U.S. Army Natick Soldier Research, Development and Engineering Center and the U.S. Army Quartermaster Center and School. In 1999, the UGR was created to simplify logistics and ensure all necessary ingredients were provided, combining elements and offerings of the A-ration, B-ration, T-ration, and commercial items. The UGR was initially trialed with the Army, with their first shipments received around 2000; the Air Force, Marine Corps, and Navy also began receiving UGRs at unspecified dates. The UGR-E was introduced in 2006. The UGR-B was phased out and replaced by the mostly similar UGR-M at an unspecified date.
A 2017 study finds that countries' coup-proofing strategies are heavily influenced by other countries with similar histories. Coup-proofing is more likely in former French colonies. A 2018 study in the Journal of Peace Research found that leaders who survive coup attempts and respond by purging known and potential rivals are likely to have longer tenures as leaders. A 2019 study in Conflict Management and Peace Science found that personalist dictatorships are more likely to take coup-proofing measures than other authoritarian regimes; the authors argue that this is because "personalists are characterized by weak institutions and narrow support bases, a lack of unifying ideologies and informal links to the ruler". In their 2022 book Revolution and Dictatorship: The Violent Origins of Durable Authoritarianism, political scientists Steven Levitsky and Lucan Way found that political-military fusion, where the ruling party is highly interlinked with the military and created the administrative structures of the military from its inception, is extremely effective at preventing military coups. For example, the People's Liberation Army was created by the Chinese Communist Party during the Chinese Civil War, and never instigated a military coup even after large-scale policy failures (i.e. the Great Leap Forward) or the extreme political instability of the Cultural Revolution. Some scholars have posited that the recruitment of foreign legionnaires into national armies can reduce the probability of military coups.
== External links == UniProt: Bisphosphoglycerate mutase - Homo sapiens (Human) UniProt-Information about bisphosphoglycerate mutase A live model of the effect of changing 2,3-bisphosphoglycerate on the oxyhaemoglobin saturation curve
Sources: en.wikipedia.org
As of 2016, challenges including optimizing sample treatment, optimizing disk surfaces, developing readers that can deploy multiple colors of light delivery and sensing for multiplexing, and for clinical use, obtaining regulatory approvals. The field is similar to lab-on-a-chip platforms. As of 2010 companies including Gyros AB, Tecan, and Burstein Technologies were working on bringing CD/DVD based immunoassays and equipment to market. Bioanalysis Microanalysis Immunoscreening List of chemical analysis methods
The second approach of bioprinting is autonomous self-assembly. This approach relies on the physical process of embryonic organ development as a model to replicate the tissues of interest. When cells are in their early development, they create their own extracellular matrix building block, the proper cell signaling, and independent arrangement and patterning to provide the required biological functions and micro-architecture. Autonomous self-assembly demands specific information about the developmental techniques of the tissues and organs of the embryo. There is a "scaffold-free" model that uses self-assembling spheroids that subjects to fusion and cell arrangement to resemble evolving tissues. Autonomous self-assembly depends on the cell as the fundamental driver of histogenesis, guiding the building blocks, structural and functional properties of these tissues. It demands a deeper understanding of how embryonic tissues mechanisms develop as well as the microenvironment surrounded to create the bioprinted tissues.
The atmospheric results were supplemented by the underground test data accumulated in the 1960s at the Nevada Test Site, as it was hoped that powerful explosions conducted in confined space might result in improved yields and heavier isotopes. Apart from traditional uranium charges, combinations of uranium with americium and thorium have been tried, as well as a mixed plutonium-neptunium charge. They were less successful in terms of yield (of material), which was attributed to stronger losses of heavy isotopes due to enhanced fission rates in heavy-element charges. Isolation of the products was found to be rather problematic, as the explosions were spreading debris through melting and vaporizing rocks under the great depth of 300–600 meters, and drilling to such depth in order to extract the products was both slow and inefficient in terms of collected volumes. Among the nine underground tests, which were carried between 1962 and 1969 and codenamed Anacostia (5.2 kilotons, 1962), Kennebec (<5 kilotons, 1963), Par (38 kilotons, 1964), Barbel (<20 kilotons, 1964), Tweed (<20 kilotons, 1965), Cyclamen (13 kilotons, 1966), Kankakee (20–200 kilotons, 1966), Vulcan (25 kilotons, 1966) and Hutch (20–200 kilotons, 1969), the last one was most powerful and had the highest yield of transuranium elements. In the dependence on the atomic mass number, the yield showed a saw-tooth behavior with the lower values for odd isotopes, due to their higher fission rates.
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.
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.