Everything below concerns Primary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2025-12-03. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
| 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. |
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.
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.
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.
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.
CPA is widely available throughout the world, and is marketed in almost every developed country, with the notable major exceptions of the United States and Japan. In almost all countries in which CPA is marketed, it is available both alone and in combination with an estrogen in birth control pills. CPA is marketed widely in combination with both ethinylestradiol and estradiol valerate. CPA-containing birth control pills are available in South Korea, but CPA as a standalone medication is not marketed in this country. In Japan and South Korea, the closely related antiandrogen and progestin chlormadinone acetate, as well as other medications, are used instead of CPA. Specific places in which CPA is marketed include the United Kingdom, elsewhere throughout Europe, Canada, Australia, New Zealand, South Africa, Latin America, and Asia. CPA is not marketed in most of Africa and the Middle East. It has been said that the lack of availability of CPA in the United States explains why there are relatively few studies of it in the treatment of androgen-dependent conditions such as hyperandrogenism and hirsutism in women.
== Limits and extensions of PBPK modeling == Each type of modeling technique has its strengths and limitations. PBPK modeling is no exception. One limitation is the potential for a large number of parameters, some of which may be correlated. This can lead to the issues of parameter identifiability and redundancy. However, it is possible (and commonly done) to model explicitly the correlations between parameters (for example, the non-linear relationships between age, body-mass, organ volumes and blood flows). After numerical values are assigned to each PBPK model parameter, specialized or general computer software is typically used to numerically integrate a set of ordinary differential equations like those described above, in order to calculate the numerical value of each compartment at specified values of time (see Software). However, if such equations involve only linear functions of each compartmental value, or under limiting conditions (e.g., when input values remain very small) that guarantee such linearity is closely approximated, such equations may be solved analytically to yield explicit equations (or, under those limiting conditions, very accurate approximations) for the time-weighted average (TWA) value of each compartment as a function of the TWA value of each specified input (see, e.g.,). PBPK models can rely on chemical property prediction models (QSAR models or predictive chemistry models) on one hand. For example, QSAR models can be used to estimate partition coefficients.
Campbell, MK (1999). Biochemistry (third ed.). Harcourt. ISBN 978-0-03-024426-1. Eshaghian, S; Horwich, TB; Fonarow, GC (2006). "An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure". Am Heart J. 151 (1): 91.e1–91.e6. doi:10.1016/j.ahj.2005.10.008. PMID 16368297. Ganong, WF (2003). Review of Medical Physiology (21st ed.). Lange. ISBN 978-0-07-140236-1. Hager, T (1995). Force of Nature: The Life of Linus Pauling. Simon and Schuster. ISBN 978-0-684-80909-0. Hazelwood, Loren (2001) Can't Live Without It: The story of hemoglobin in sickness and in health, Nova Science Publishers ISBN 1-56072-907-4 Kneipp J, Balakrishnan G, Chen R, Shen TJ, Sahu SC, Ho NT, Giovannelli JL, Simplaceanu V, Ho C, Spiro T (2005). "Dynamics of allostery in hemoglobin: roles of the penultimate tyrosine H bonds". J Mol Biol. 356 (2): 335–53. doi:10.1016/j.jmb.2005.11.006. PMID 16368110. Hardison, Ross C. (2012). "Evolution of Hemoglobin and Its Genes". Cold Spring Harbor Perspectives in Medicine. 2 (12) a011627. doi:10.1101/cshperspect.a011627. ISSN 2157-1422. PMC 3543078. PMID 23209182.
== Design == The newer TGI Fridays franchises (as well as redesigned restaurants) are more contemporary, with wallpaper, granite exteriors, and red-and-white striped lamps instead of Tiffany. The exteriors have stucco, the entrance doors have F-shaped handles, and a metal cup above the door has a stripe saying "In Here, It's always Friday". The logo design was evolved in 2013 by Jane MacDowall and her creative team in Scotland. Most TGI Fridays have a propeller and a rowing scull on display as part of their antiques, which are actually a part of a story told to all TGI Fridays employees; the scull always contains a pair of saddle shoes and a bottle of champagne to remind employees of the value of teamwork, leadership, and celebrating success. The propeller is always above or near the bar. The thought is that the bar "propels" the restaurant.
Etoxeridine (Carbetidine, Atenos) is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). Etoxeridine was developed in the 1950s and investigated for use in surgical anesthesia, however it was never commercialized and is not currently used in medicine. As with other opioids which were not in clinical use during the drafting of the Controlled Substances Act, it is categorized as a Schedule I narcotic.
Sources: en.wikipedia.org
First known as "emanation", the radioactive gas was identified during experiments with radium, thorium oxide, and actinium by Friedrich Ernst Dorn, Rutherford and Owens, and André-Louis Debierne, respectively, and each element's emanation was considered to be a separate substance: radon, thoron, and actinon. Sir William Ramsay and Robert Whytlaw-Gray considered that the radioactive emanations may contain a new element of the noble gas family, and isolated "radium emanation" in 1909 to determine its properties. In 1911, the element Ramsay and Whytlaw-Gray isolated was accepted by the International Commission for Atomic Weights, and in 1923, the International Committee for Chemical Elements and the International Union of Pure and Applied Chemistry (IUPAC) chose radon as the accepted name for the element's most stable isotope, 222Rn; thoron and actinon were also recognized by IUPAC as distinct isotopes of the element. A common source of environmental radon is uranium-containing minerals in the ground. Radon can also occur in ground water, such as spring waters and hot springs. Radon trapped in permafrost may be released by climate-change-induced thawing of permafrosts, and radon may also be released into groundwater and the atmosphere following seismic events leading to earthquakes, which has led to its investigation in the field of earthquake prediction. It is possible to test for radon in buildings, and to use techniques such as sub-slab depressurization for mitigation.
== Clinical significance == Furin is one of the proteases responsible for the proteolytic cleavage of HIV envelope polyprotein precursor gp160 to gp120 and gp41 prior to viral assembly. This protease is also thought to play a role in tumor progression. The use of alternate polyadenylation sites has been found for the FURIN gene. Furin is enriched in the Golgi apparatus, where it functions to cleave other proteins into their mature/active forms. Furin cleaves proteins just downstream of a basic amino acid target sequence (canonically, Arg-X-(Arg/Lys) -Arg'). In addition to processing cellular precursor proteins, furin is also used by a number of pathogens. For example, the envelope proteins of viruses such as HIV, influenza, dengue fever, several filoviruses including ebola and marburg virus, and the spike protein of SARS-CoV-2, must be cleaved by furin or furin-like proteases to become fully functional. When SARS-CoV-2 virus is being synthesized in an infected cell, furin or furin-like proteases cleave the spike protein into two portions (S1 and S2), which remain associated. Anthrax toxin, Pseudomonas exotoxin, and papillomaviruses must be processed by furin during their initial entry into host cells. Inhibitors of furin are under consideration as therapeutic agents for treating anthrax infection. Furin is regulated by cholesterol and substrate presentation. When cholesterol is high, furin traffics to GM1 lipid rafts. When cholesterol is low, furin traffics to the disordered region. This is speculated to contribute to cholesterol and age dependent priming of SARS-CoV.
Józef Piłsudski signs a decree officially allowing 16 MPs from the Prussian Partition to participate in Sejm Ustawodawczy. 9 February 1919: The Poles stop a German offensive near Trzciel. 10 February 1919: The Poles stop a German attack near Rawicz. 11 February 1919: The Commission of the NRL dissolves all town councils, giving 25 March as date of new elections. 12 February 1919: Germans use an armoured train to capture Kargowa and Babimost, but their offensive is stopped near Kopanica. 14 February 1919 Talks start on extending the ceasefire that ended World War I. The German delegation is against extending it for Greater Poland, but France forces it through. The German headquarters is moved to Kolberg, as a part of preparations to use all forces against Greater Poland. 16 February 1919: The extension of the Allied-German ceasefire in Trier is signed, which also refers to Greater Poland. The Polish army is referred to as Allied forces. A military demarcation line was established.
In the United States, it was once widely used as a food additive in root beer, sassafras tea, and other common goods, but was banned for human consumption by the FDA after studies in the 1960s suggested that safrole was carcinogenic, causing permanent liver damage in rats; food products sold there purporting to contain sassafras instead contain a safrole-free sassafras extract. Safrole is also banned for use in soap and perfumes by the International Fragrance Association. According to a 1977 study of the metabolites of safrole in both rats and humans, two carcinogenic metabolites of safrole found in the urine of rats, 1′-hydroxysafrole and 3′-hydroxyisosafrole, were not found in human urine. The European Commission on Health and consumer protection assumes safrole to be genotoxic and carcinogenic. It occurs naturally in a variety of spices, such as cinnamon, nutmeg, and black pepper, and herbs such as basil. In that role, safrole, like many naturally occurring compounds, may have a small but measurable ability to induce cancer in rodents. Despite this, the effects in humans were estimated by the Lawrence Berkeley National Laboratory to be similar to risks posed by breathing indoor air or drinking municipally supplied water.
Sources: en.wikipedia.org
7-Eleven, Inc. is an American convenience store chain headquartered in Irving, Texas. It is a wholly owned subsidiary of Seven-Eleven Japan, which is owned by Seven & I Holdings, a Japanese retail holding company. The chain was founded in 1927 as the Southland Ice Company, operating an ice house storefront in Dallas. Owned by the Southland Corporation, the chain expanded its convenience stores and renamed them Tote'm Stores between 1928 and 1946. The Southland Corporation changed the stores' name to 7-Eleven in 1946 to reflect their expanded hours of operation (7 a.m. to 11 p.m.). The Southland Corporation started franchising its stores in 1961. In 1973, Ito-Yokado, a Japanese supermarket chain, signed a franchise agreement with the Southland Corporation to develop 7-Eleven convenience stores in Japan. Later in 1991, operating the Japanese stores under Seven-Eleven Japan, Ito-Yokado acquired a 70% stake in the Southland Corporation. As the majority owner, it changed the Southland Corporation's name to 7-Eleven, Inc. Ito-Yokado expanded to 100% ownership in November 2005, making 7-Eleven, Inc. a wholly owned subsidiary of Seven-Eleven Japan. That same year, Ito-Yokado reorganized its collective businesses into the holding company Seven & I Holdings, with 7-Eleven, Inc. remaining wholly held by Seven-Eleven Japan. 7-Eleven operates, franchises, and licenses roughly 85,000 stores in 20 countries and territories as of August 2024. Its stores operate under its namesake brand globally.
Under Lenin, the government gave small language groups their own writing systems. The development of these writing systems was highly successful, even though some flaws were detected. During the later days of the USSR, countries with the same multilingual situation implemented similar policies. A serious problem when creating these writing systems was that the languages differed dialectally greatly from each other. When a language had been given a writing system and appeared in a notable publication, it would attain 'official language' status. There were many minority languages which never received their own writing system; therefore, their speakers were forced to have a second language. There are examples where the government retreated from this policy, most notably under Stalin where education was discontinued in languages that were not widespread. In 1938, Stalin mandated all schools to teach Soviet schoolchildren the Russian language. It did not stop children from getting an education in their native language (the language they grew up speaking), but they would also be required to learn how to speak the Russian language. Stalin saw this as necessary from a military perspective, because it would be easier for everyone to communicate. Despite only being mandated in 1938, children of different ethnicities were already being enrolled in schools teaching Russian beforehand because knowing the Russian language would open up a lot of opportunities for a person.
Organelles are compartments of the cell that are specialized for carrying out one or more functions, analogous to the organs, such as the heart, and lungs. There are several types of organelles held in the cytoplasm. Most organelles are membrane-bound, and vary in size and number based on the growth of the host cell. Organelles include the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, peroxisomes, vesicles, and vacuoles. Membrane-less organelles include the nucleolus in the nucleus, centrosomes, ribosomes, proteasomes, and vaults.
=== Early career (1986–1991) === Steve Austin began his wrestling training in 1986 under Chris Adams at the Dallas Sportatorium, when Adams was affiliated with World Class Wrestling Association (WCWA, formerly WCCW). Although the training emphasized technical skills, Austin later expressed dissatisfaction with the lack of instruction on the business side of wrestling. Austin made his in-ring debut later that year in a televised WCWA match using his real name at the time, Steve Williams. During the merger of WCWA and the Memphis-based Continental Wrestling Association into the United States Wrestling Association (USWA), he began wrestling under the name "Steve Austin", a change made to avoid confusion with "Dr. Death" Steve Williams. He competed primarily in Dallas and was managed by Percy Pringle (later known as Paul Bearer in WWF) during this period. One of his early storylines involved a feud with his trainer, Chris Adams.
m2 or 131.2 hectares. In a graphene sheet, each atom is connected to its three nearest carbon neighbors by σ-bonds, and a delocalized π-bond, which contributes to a valence band that extends over the whole sheet. This type of bonding is also seen in polycyclic aromatic hydrocarbons. The valence band is touched by a conduction band, making graphene a semimetal with unusual electronic properties that are best described by theories for massless relativistic particles. Charge carriers in graphene show linear, rather than quadratic, dependence of energy on momentum, and field-effect transistors with graphene can be made that show bipolar conduction. Charge transport is ballistic over long distances; the material exhibits large quantum oscillations and large nonlinear diamagnetism.
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.
Conventional drying uses heat to evaporate water from a material, while lyophilization freezes the material and removes water by sublimation under vacuum. This avoids the liquid phase and reduces thermal damage to sensitive substances. The result is a porous cake that reconstitutes quickly.