The short version of primary drying fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-04-26. Anything still debated is marked as such rather than presented as settled.
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.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying; lyophilisation; cryodesiccation | Regional spelling and historical terms. |
| Primary drying pressure | 0.05-0.5 mbar (5-50 Pa) | Kept below the triple point of water; product-specific. |
| Shelf temperature range | -40 to +40 °C | Freezing, primary, and secondary stages use different set points. |
| Cycle duration | 12-72 hours | Depends on fill volume, formulation, and equipment. |
| Condenser temperature | -50 to -80 °C | Must remain below the product's ice temperature. |
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 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.
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, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
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.
It was commonly believed that cardiac muscle cells could not be regenerated. However, this was contradicted by a report published in 2009. Olaf Bergmann and his colleagues at the Karolinska Institute in Stockholm tested samples of heart muscle from people born before 1955 who had very little cardiac muscle around their heart, many showing with disabilities from this abnormality. By using DNA samples from many hearts, the researchers estimated that a 4-year-old renews about 20% of heart muscle cells per year, and about 69% of the heart muscle cells of a 50-year-old were generated after they were born. One way that cardiomyocyte regeneration occurs is through the division of pre-existing cardiomyocytes during the normal aging process. In the 2000s, the discovery of adult endogenous cardiac stem cells was reported, and studies were published that claimed that various stem cell lineages, including bone marrow stem cells were able to differentiate into cardiomyocytes, and could be used to treat heart failure. However, other teams were unable to replicate these findings, and many of the original studies were later retracted for scientific fraud.
== Production == Putrescine is produced on an industrial scale by the hydrogenation of succinonitrile. Biotechnological production of putrescine from a renewable feedstock has been investigated. A metabolically engineered strain of Escherichia coli that produces putrescine at high concentrations in glucose mineral salts medium has been described.
== Medical uses == The safety and efficacy of trastuzumab-containing combination therapies (with chemotherapy, hormone blockers, or lapatinib) for the treatment of metastatic breast cancer. The overall hazard ratios (HR) for overall survival and progression free survival were 0.82 and 0.61, respectively. It was difficult to accurately ascertain the true impact of trastuzumab on survival, as in three of the seven trials, over half of the patients in the control arm were allowed to cross-over and receive trastuzumab after their cancer began to progress. Thus, this analysis likely underestimates the true survival benefit associated with trastuzumab treatment in this population. In early-stage HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (Hazard ratio (HR) = 0.66) and disease-free survival (HR = 0.60). Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction (relative risk RR = 1.83) were seen in these trials as well. Two trials involving shorter term treatment with trastuzumab did not differ in efficacy from longer trials, but produced less cardiac toxicity. The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early-stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within three years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%.
) is typically set to a value of 1 to increase the readability of the exchangeability parameter estimates (since it allows users to express those values relative to chosen exchangeability parameter). The practice of expressing the exchangeability parameters in relative terms is not problematic because the
== Law enforcement and defence == Founded in 1981, the Ciskei Defence Force consisted of two battalions and an air wing. Ciskei Police Ciskei Police – Law Enforcement Division Ciskei Prisons Service Ciskei Traffic Force
Sources: en.wikipedia.org
Rather than finding homologous proteins from different species, a new Tag/Catcher pair was developed from SpyTag/SpyCatcher with minimal mutations. SpyTag I3W (AW) reacts with SpyCatcher F77V, F94A (BVA) but minimally with SpyCatcher, whereas SpyCatcher F77V, F94A can react with both SpyTag I3W and SpyTag. However, the cross-reactivity of SpyCatcher F77V, F94A with both SpyTag versions may limit its utility as a new Tag/Catcher pair. A different chemistry can be exploited for protein ligation: the discovery of an intramolecular ester bond formation in Clostridium perfringens cell-surface adhesin protein Cpe0147 led to the development of another Tag/Catcher pair with Cpe0147565–587 as the Tag and Cpe0147439–563 as the Catcher. The ester bond formed between Thr-Gln is irreversible, however by mutating the Thr to Ser, the Ser-Gln ester bond is reversible with a change of pH.
== Corporate governance == As of July 2026, Biocon remains chaired by Mazumdar-Shaw. Effective 1 April 2026, Shreehas Tambe was appointed Chief Executive Officer and Managing Director of Biocon Limited—the first CEO of the integrated company following the full integration of Biocon Biologics Limited as a wholly owned subsidiary; Kedar Upadhye was appointed Chief Financial Officer. Tambe succeeded Siddharth Mittal, who resigned effective 31 March 2026 and moved to another leadership role within the Biocon Group. Mittal had led the company since December 2019, when he replaced CEO and Managing Director Arun Chandavarkar. In 2021, Christiane Hamacher resigned as CEO of Biocon Biologics India Limited, following differences with Mazumdar-Shaw. Hamacher had been appointed to that role in March 2019.
The working group defined four criteria that must be fulfilled: "like-mindedness", "significant player", "mutual benefit" and "global considerations." The working group's recommendations were presented at the OECD Ministerial Council Meeting on 13 May 2004, and on 16 May 2007, the OECD Ministerial Council decided to open accession discussions with Chile, Estonia, Israel, Russia, and Slovenia, and to strengthen cooperation with Brazil, China, India, Indonesia, and South Africa through a process of enhanced engagement. Chile, Slovenia, Israel, and Estonia all became members in 2010. In March 2014, the OECD halted membership talks with Russia in response to its annexation of Crimea. In 2013, the OECD decided to open membership talks with Colombia and Latvia. In 2015, the Organisation opened talks with Costa Rica and Lithuania. Latvia became a member on 1 July 2016, and Lithuania soon followed on 5 July 2018. Colombia signed the accession agreement on 30 May 2018 and became a member on 28 April 2020. On 15 May 2020, the OECD decided to extend a formal invitation for Costa Rica to join the OECD, which joined as a member on 25 May 2021. Other countries that have expressed interest in OECD membership are Argentina, Brazil, Croatia, Malaysia and Peru. In January 2022, the OECD reported that membership talks were underway with Argentina, Brazil, Bulgaria, Croatia, Peru and Romania. In March 2022, the OECD suspended the participation of Russia and Belarus due to the ongoing Russian invasion of Ukraine.
===== Oxygen isotope anomaly ===== The comparison of coral strontium/calcium minimums with sea surface temperature maximums, data recorded from NINO 3.4 SSTA, time can be correlated to coral strontium/calcium and δ18O variations. To confirm the accuracy of the annual relationship between Sr/Ca and δ18O variations, a perceptible association to annual coral growth rings confirms the age conversion. Geochronology is established by the blending of Sr/Ca data, growth rings, and stable isotope data. El Nino-Southern Oscillation (ENSO) is directly related to climate fluctuations that influence coral δ18O ratio from local salinity variations associated with the position of the South Pacific convergence zone (SPCZ) and can be used for ENSO modeling.
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=== Cultivation === The saffron crocus, unknown in the wild, probably descends from Crocus cartwrightianus. It is a triploid that is "self-incompatible" and male sterile; it undergoes aberrant meiosis and is hence incapable of independent sexual reproduction—all propagation is by vegetative multiplication via manual "divide-and-set" of a starter clone or by interspecific hybridisation. Crocus sativus thrives in the Mediterranean maquis, an ecotype superficially resembling the North American chaparral, and similar climates where hot and dry summer breezes sweep semi-arid lands. It can nonetheless survive cold winters, tolerating frosts as low as −10 °C (14 °F) and short periods of snow cover. Some reports suggest saffron can tolerate an air temperature range from −22 to 40 °C. Irrigation is required if grown outside of moist environments such as Kashmir, where annual rainfall averages 1,000–1,500 mm (40–60 in); saffron-growing regions in Greece (500 mm or 20 in annually) and Spain (400 mm or 16 in) are far drier than the main cultivating Iranian regions. What makes this possible is the timing of the local wet seasons; generous spring rains and drier summers are optimal. Rain immediately preceding flowering boosts saffron yields; rainy or cold weather during flowering promotes disease and reduces yields. Persistently damp and hot conditions harm the crops, and rabbits, rats, and birds cause damage by digging up corms. Nematodes, leaf rusts, and corm rot pose other threats.
== Neutron poisoning == A reactor can be unintentionally "shut down" by having an excess of neutron poisons in the reactor vessel. Neutron poisons are chemical byproducts of the nuclear reaction which absorb neutrons, lowering reactivity in the reactor and potentially stalling the reaction if enough poisons are allowed to build up. An example of this would be the Chernobyl disaster in 1986, when Reactor No. 4 suffered from a serious xenon-135 poisoning, which pushed the reactor into an unstable condition which later caused the accident. While neutron poisoning is not considered a shutdown in and of itself, it often requires that the reactor be shut down while the poisons are flushed from the system, as they can destabilise the reactor and cause it to behave unpredictably. Certain reactors, such as the CANDU reactor design (where it is called EPIS, or Emergency Poison Injection System), employ this phenomenon as part of their SCRAM procedure. When a SCRAM occurs, neutron poisons are injected into the reactor to immediately lower the reactivity of the reactor, at the same time or slightly prior to other shutdown mechanisms, such as control rods.
=== Drugs of abuse === Synthetic cannabinoids Cocaine LSD Opiates (e.g., fentanyl, oxycodone, heroin, codeine, and morphine) Amphetamines (e.g., MDMA (Ecstasy), MDA, Meth) "Bath salts" (e.g., cathinone, synthetic cathinone, MDPV) GHB Phencyclidine (PCP)
On 17 May 2022, militias attacked a civilian helicopter that was flying over the Rio area with rifles. No injuries were recorded but the helicopter suffered slight damage. On 20 August of the same year, Delson Lima Neto, brother of one of the leader of the militias, Tandera Danilo Dias Lima, was killed alongside 3 paramilitaries soldiers by the Polícia Militar on Nova Iguaçu, in Baixada Fluminense, after his death the Comando Vermelho conquered the favela of Grão-Pará, in Nova Iguaçu. After the raid, on 23 August, the police found and seized an improvised fighting vehicle (similar to a Caveirão) used by the militias to fight against Comando Vermelho in Nova Iguaçu. According to law student Carlos Gilberto Martins Junior of Brazil in 2023, with emphasis on the State of Rio de Janeiro, there has been an arbitrary use of these powers and attributions, conferred on police institutions, to satisfy the patrimonial aspirations of some of its agents, through territorial domination and violence, to the detriment of the peripheral communities and under the pretext of saving them from the "greater evil" represented by drug trafficking, corroborating the emergence of criminals organizations what conventionally called the "militia". On 6 May 2021, at least 29 people were killed in a shootout between gangsters of Comando Vermelho and police. On May 24 2022, the BOPE raided the Vila Cruzeiro favela in Penha Complex, killing 26 people between civilians and gangsters of Comando Vermelho.
Ammonium acetate, also known as spirit of Mindererus in aqueous solution, is a chemical compound with the formula NH4CH3CO2. It is a white, hygroscopic solid and can be derived from the reaction of ammonia and acetic acid. It is available commercially.
Sources: en.wikipedia.org
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.
Reduced pressure lowers the boiling point of water and allows ice to sublime at temperatures below freezing. It also helps remove water vapor from the product toward the condenser. The exact pressure is chosen to stay below the triple point of water.
No. Materials with low solids content or high volatile solvents may form weak or collapsed cakes. Some proteins and cells require stabilizers to survive freezing and drying stresses. Feasibility depends on formulation and process design.
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.