Everything below concerns Sublimation. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-05-23. Where a claim depends on a specific study, the study is described rather than over-claimed.
Freezing is the first stage and sets the ice structure that later becomes the pore network. The formulation is cooled below its freezing point, often with a controlled ramp, and solutes concentrate as ice forms. Primary drying then lowers chamber pressure and supplies heat to sublime the ice. The product temperature must stay below its collapse or eutectic temperature to prevent structural loss. Secondary drying raises the temperature modestly to remove bound water and achieve a low residual moisture.
A freeze-dryer consists of a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. Vials, ampoules, or bulk trays hold the product during the cycle. The condenser traps water vapor as ice at a temperature lower than the product. Cycle development balances shelf temperature, chamber pressure, and time. Scale-up can be difficult because heat and mass transfer change with equipment size, so process analytical tools and conservative validation are often used.
Lyophilization is a dehydration technique in which a product is frozen and the solvent is removed under reduced pressure. The low pressure allows ice to sublimate directly into vapor without passing through a bulk liquid phase. This differs from conventional drying, where heat drives evaporation and can damage heat-sensitive structures. The process is used for biological materials, pharmaceutical formulations, and some foods. Its main advantage is preservation of porous structure and rapid reconstitution.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | freeze-drying, lyophilisation, cryodesiccation | Lyophilization is common in pharmaceutical literature. |
| Typical chamber pressure during primary drying | 0.05–0.5 mbar (5–50 Pa) | Must remain below the triple point of water. |
| Typical shelf temperature during freezing | −40 to −20 °C | Lower temperatures may be used for eutectic systems. |
| Typical residual moisture after secondary drying | 0.5–3% w/w | Product-dependent; low moisture improves stability but can cause over-drying. |
| Typical analytical method for residual moisture | Karl Fischer titration or loss on drying | Thermogravimetric methods are also used. |
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.
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.
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.
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.
==== Cave 60: "Largest Cave" ==== Cave 60, also called the "Largest Cave", is a cave which was expanded over several periods, and still contained a few paintings belonging to the refined style of the Classical First Period, while most of the paintings are from the later Second Period. The cave is known for its portrait of royal donors, characteristically accompanied by a label in Brahmi script. This is the only known possible instance of a portrait of royal donors in a painting of the First Style, whereas they occur very often during the second period. The style of painting is very similar to that seen in the Cave of the Painters (Cave 207). The hairstyle of the male donor is quite similar to that of the famous painter in the Cave of the Painters. The cave is also remarkable for the presence of Sasanian-style ducks in a bead roundel frames, a well-known motif which spread through Central Asia, and is known from the dress of a Central Asian ambassador from Afrasiab. This motif was likely painted later than the portraits of the royal donors.
The word "aptamer" is a neologism coined by Andrew D. Ellington and Jack Szostak in their first publication on the topic. They did not provide a precise definition, stating "We have termed these individual RNA sequences 'aptamers', from the Latin aptus, to fit." The word itself, however, derives from the Greek word ἅπτω, to connect or fit (as used by Homer (c. 8th century BC)) and μέρος, a component of something larger. A typical aptamer is a synthetically generated ligand exploiting the combinatorial diversity of DNA, RNA, XNA, or peptide to achieve strong, specific binding for a particular target molecule or family of target molecules. Aptamers are occasionally classified as "chemical antibodies" or "antibody mimics". However, most aptamers are small, with a molecular weight of 6-30 kDa, in contrast to the 150 kDa size of antibodies, and contain one binding site rather than the two matching antigen binding regions of a typical antibody.
Marcey Lynn Waters is the Glen H. Elder Jr., Distinguished Professor of Chemistry at the University of North Carolina, Chapel Hill (UNC-CH). She is an organic chemist whose research is at the interface of chemical biology and supramolecular chemistry. Waters has received multiple awards for research, teaching, and advocating for women in science. She served as president of the American Peptide Society (APS) from 2017 to 2019. Waters graduated from the University of California, San Diego with a degree in chemistry in 1992. While an undergraduate, she worked with Prof. Charles L. Perrin studying fundamental aspects of aromaticity. Waters entered the University of Chicago for her doctoral degree in chemistry, working with Prof. William D. Wulff studying the mechanism for the Wulff-Dotz benzannulation reaction between Fischer carbene complexes. and alkynes. Walters graduated from Chicago in 1997 with a PhD in chemistry. She was an NIH postdoctoral fellow in Prof. Ronald Breslow's group from 1997 to 1999, where she worked on dinuclear metalloenzyme mimics and antiaromaticity.
Ca2+ + 2 HCO−3 → CaCO3↓ + CO2 + H2O At seawater pH, most of the dissolved CO2 is immediately converted back into HCO−3. The reaction results in a net transport of one molecule of CO2 from the ocean/atmosphere into the lithosphere. The result is that each Ca2+ ion released by chemical weathering ultimately removes one CO2 molecule from the surficial system (atmosphere, ocean, soil and living organisms), storing it in carbonate rocks where it is likely to stay for hundreds of millions of years. The weathering of calcium from rocks thus scrubs CO2 from the ocean and air, exerting a strong long-term effect on climate.
== Lawsuits == In 2009, Pfizer resolved all but three of 35,000 claims over its withdrawn diabetes drug Rezulin for a total of about $750 million. Pfizer, which acquired rival Wyeth for almost $64 billion, paid about $500 million to settle Rezulin cases consolidated in federal court in New York, according to court filings. The company also paid as much as $250 million to resolve state-court suits. In 2004, it set aside $955 million to end Rezulin cases.
Sources: en.wikipedia.org
=== Classical === These types of NLSs can be further classified as either monopartite or bipartite. The major structural differences between the two are that the two basic amino acid clusters in bipartite NLSs are separated by a relatively short spacer sequence (hence bipartite - 2 parts), while monopartite NLSs are not. The first NLS to be discovered was the sequence PKKKRKV in the SV40 Large T-antigen (a monopartite NLS). The NLS of nucleoplasmin, KR[PAATKKAGQA]KKKK, is the prototype of the ubiquitous bipartite signal: two clusters of basic amino acids, separated by a spacer of about 10 amino acids. Both signals are recognized by importin α. Importin α contains a bipartite NLS itself, which is specifically recognized by importin β. The latter can be considered the actual import mediator. Chelsky et al. proposed the consensus sequence K-K/R-X-K/R for monopartite NLSs. A Chelsky sequence may, therefore, be part of the downstream basic cluster of a bipartite NLS. Makkah et al. carried out comparative mutagenesis on the nuclear localization signals of SV40 T-Antigen (monopartite), C-myc (monopartite), and nucleoplasmin (bipartite), and showed amino acid features common to all three. The role of neutral and acidic amino acids was shown for the first time in contributing to the efficiency of the NLS. Rotello et al. compared the nuclear localization efficiencies of eGFP fused NLSs of SV40 Large T-Antigen, nucleoplasmin (AVKRPAATKKAGQAKKKKLD), EGL-13 (MSRRRKANPTKLSENAKKLAKEVEN), c-Myc (PAAKRVKLD) and TUS-protein (KLKIKRPVK) through rapid intracellular protein delivery.
EDTA can also be used to test for bioavailability of heavy metals in sediments. However, it may influence the bioavailability of metals in solution, which may pose concerns regarding its effects in the environment, especially given its widespread uses and applications.
Metabolites produced from vitamin D2 tend to bind less well to the vitamin D-binding protein. Vitamin D3 can alternatively be hydroxylated to calcifediol by sterol 27-hydroxylase, an enzyme coded for by gene CYP27A1, but vitamin D2 cannot. Ergocalciferol can be directly hydroxylated at position 24 by the enzyme coded for by CYP27A1. This hydroxylation also leads to a greater degree of inactivation: the activity of calcitriol decreases to 60% of original after 24-hydroxylation, whereas ercalcitriol undergoes a 10-fold decrease in activity on conversion to ercalcitetrol.
According to the US, in 2024, China continues to be the primary supplier of chemical precursors to Mexican drug cartels, and Chinese money launderers have become central to the global drug trade. In December 2024, a Chinese national in Chicago was sentenced to 10 years in prison laundering $62 million in drug money for Mexican traffickers involving currency swaps between United States and China, and China and Mexico. In January 2025, two former executives of a Chinese chemical company were convicted of a scheme to import fentanyl precursor chemicals into the United States. One was sentenced to 25 years in prison and the other to 15 years.
Sources: en.wikipedia.org
Yes, the terms are generally interchangeable. Lyophilization is more common in pharmaceutical and laboratory contexts, while freeze-drying appears widely in food science and general writing. Both describe removal of solvent by sublimation under vacuum after freezing.
Reduced pressure keeps the process below the triple point of water, so ice can sublimate directly to vapor. It also lowers the temperature needed for drying, which helps preserve heat-sensitive materials. Without vacuum, melting or boiling could occur instead of controlled sublimation.
The rate depends on heat transfer to the product and mass transfer of vapor through the dried layer. A cold condenser, adequate vacuum, and suitable shelf temperature all influence speed. Formulation properties such as solid content and collapse temperature also set practical limits.
The main change is sublimation, in which ice becomes water vapor without melting into liquid water. This occurs when the chamber pressure is held below the vapor pressure of ice while mild heat is supplied. The result is a dry, porous solid that retains much of its original shape.