This is a working overview of glass transition, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-05-03 and is reviewed periodically as new material appears.
Stability studies examine how temperature, humidity, and time influence a lyophilized product. Accelerated conditions provide early information about degradation pathways, while long-term studies support shelf-life claims. The glass transition temperature of the dried formulation can indicate its physical stability, and storage above this temperature may increase molecular mobility and lead to collapse or aggregation. Container closure integrity also matters because moisture or oxygen ingress can degrade the product, so vial stoppers and seals are part of the quality system.
Handling and storage practices aim to keep the cake intact and dry. Vials are typically stored upright at controlled temperatures, often between 2 °C and 8 °C or at -20 °C for longer-term use. Reconstitution involves adding a suitable diluent and gently mixing until the solid dissolves. Shaking or rapid injection of diluent can create foam or damage sensitive molecules. Once reconstituted, the product may require refrigeration and use within a defined period.
Residual moisture is a key quality attribute for lyophilized products. Water that remains after secondary drying can affect chemical stability, cake structure, and shelf life. Karl Fischer titration is a common method for measuring water content in the dried solid. The target range varies by product, but many biologics are dried to between 0.5% and 3% water by weight. Acceptable limits are set during development and confirmed by stability studies.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Residual moisture | 0.5-3% w/w | Typical range for many biopharmaceuticals |
| Typical storage temperature | 2-8 °C | Some products require -20 °C or lower |
| Reconstitution time | Seconds to several minutes | Depends on cake porosity and diluent |
| Common moisture method | Karl Fischer titration | Measures water content in the solid |
| Container closure | Stoppered vial with seal | Protects against moisture and oxygen ingress |
Stability programs monitor lyophilized products under defined temperature and humidity conditions over time. Real-time studies at recommended storage conditions are the reference, while accelerated studies provide early signals of degradation pathways. Because a dry cake can still undergo oxidation, hydrolysis, or aggregation, stability depends on residual moisture, excipients, and container headspace. Open questions include how best to predict long-term stability from short accelerated runs and how vial-to-vial variability affects shelf life. Current guidance treats these predictions as product-specific rather than universally generalizable.
Freeze-dried materials are hygroscopic to varying degrees and can take up moisture after drying. Storage therefore often uses sealed glass vials, rubber stoppers, and crimp seals to limit contact with ambient humidity. A desiccant may be included for moisture-sensitive products, although it is not universal. Controlled room temperature is sufficient for many lyophilizates, while others require refrigeration or freezing. Moisture ingress remains a primary cause of cake collapse, chemical degradation, and loss of reconstitution performance.
The physics of lyophilization couples heat transfer, mass transfer, and phase behavior. Sublimation requires a vapor pressure difference between the ice front and the chamber, and the dried layer adds resistance to vapor flow. Amorphous formulations are characterized by a glass transition temperature of the maximally freeze-concentrated solute, often denoted Tg'. Crystalline bulking agents can provide structure, while amorphous excipients stabilize labile components. Open questions remain about spatial heterogeneity, edge effects, and how laboratory cycles scale to production.
Lyophilization is a drying process in which a solvent, usually water, is removed from a frozen material by sublimation under reduced pressure. The material is first solidified, then placed under vacuum so that ice transitions directly to vapor without a bulk liquid phase. This approach suits heat-sensitive substances that would degrade during conventional evaporation. Primary drying removes unbound ice, while secondary drying reduces water that remains adsorbed to the solid matrix. The result is a porous, lightweight solid that can be reconstituted later.
A typical cycle begins with freezing, sometimes including an annealing step to control ice crystal size. Freezing conditions influence the pore network that later allows vapor escape. During primary drying, shelf temperature and chamber pressure are set so heat enters the product while its temperature stays below the collapse or eutectic point. Secondary drying then raises the shelf temperature to desorb bound water and lower residual moisture. Cycle design depends on formulation, fill volume, container type, and equipment capability.
Stability of a lyophilized product depends on its glass transition temperature, the temperature at which the amorphous cake transitions from a glassy to a rubbery state. Storage below this temperature minimizes molecular mobility and slows chemical degradation. If the storage temperature exceeds the glass transition temperature, the cake may collapse, shrink, or become sticky. Accelerated stability studies at elevated temperatures and humidity help predict shelf life, but they do not always reflect real-time behavior. Residual moisture content also plays a critical role in long-term stability.
Reconstitution involves adding a suitable diluent, often sterile water or a buffer, to the dried cake. Gentle swirling or inversion helps dissolve the material without creating excessive foam. The time required for complete dissolution can range from seconds to several minutes and depends on the cake structure and the diluent. Improper reconstitution, such as vigorous shaking or using the wrong diluent, can cause protein aggregation or loss of activity. After reconstitution, the product may have a limited shelf life and should be used according to its labeling.
Lyophilized products are typically hygroscopic and require protection from moisture during storage. Manufacturers seal them in glass vials, often under vacuum or an inert gas such as nitrogen. The container closure system, including the stopper and crimp seal, must prevent water vapor ingress. Storage temperature varies from controlled room temperature to refrigerated or frozen conditions, depending on the formulation. Humidity-controlled environments are essential because even brief exposure to ambient air can degrade the product.
In the 2018 legislative and municipal elections, where Bukele was favored to win re-election before his expulsion, the FMLN had its worst performance since 1994, the party's first election. It lost six seats in the Legislative Assembly, and 16 municipalities. During the election, Bukele called on his supporters nationwide to spoil their vote or stay home on election day rather than support the FMLN. In February 2019, FMLN presidential communications secretary Roberto Lorenzana stated that Bukele's expulsion was a mistake that cost the party votes. In 2025, Bukele remarked that he was "mistaken" ("equivocado") for having previously voted for the FMLN.
Shephard was planned to be the player character of Arkane Studios' Ravenholm spinoff game, developed around 2007 to 2008, a project which Valve later cancelled. Valve also affirmed that Shephard had no connection to Portal after players found that the keyboard images in game showed the lit characters "ASHPD" and believed that hinted at Shephard's return; the letters instead referred to the long name of the "Aperture Science Handheld Portal Device" also known as the "portal gun", with the nearness to Shephard's name a "total freak coincidence" according to Valve's Doug Lombardi.
=== Stable vs radioactive isotopes === All isotopes of an element have the same number of protons with varying numbers of neutrons. Hydrogen has three naturally occurring isotopes: 1H, 2H and 3H; called protium (H), deuterium (D) and tritium (T), respectively. Both 1H and 2H are stable, while 3H is unstable and beta-decays to 3He. While there are some important applications of 3H in geochemistry (such as its use as an ocean circulation tracer) these will not be discussed further here.
=== Private jet controversy === In April 2026, Ford's government purchased a $28.9 million Bombardier 650 luxury private jet, intended to be used by the premier for travel. After backlash from the public and opposition parties, the government announced their intention to sell the jet.
== Management == Katherine Stueland was appointed CEO of GeneDx in 2021. Under her leadership, the company refocused its operations on exome and genome sequencing for rare disease diagnosis. Stueland has been recognized for her work in genomic medicine, including being named to CNBC's Changemakers list in 2025 and to the TIME100 Health list in 2026. Kevin Feeley was appointed CFO in 2022. Prior to joining GeneDx, Feeley served as CFO of BioReference Laboratories and held senior roles at KPMG LLP. Bryan Dechairo was appointed COO in 2025.
Sources: en.wikipedia.org
== Research contributions == Balalaie's research focuses on several areas of organic chemistry, including environmentally friendly synthetic methods and pharmaceutical applications. His research group has worked on the development of multicomponent reactions (MCRs), particularly for the synthesis of heterocyclic compounds. His work in this area has included the use of zeolite catalysts for the preparation of tetrasubstituted imidazoles and other heterocycles. His research has also involved developing synthetic routes for several active pharmaceutical ingredients (APIs). Compounds published by his group include: Zoledronic acid, Gabapentin, Deferasirox and Pantoprazole. In peptide synthesis, Balalaie's work has included the synthesis of therapeutic peptides such as triptorelin, leuprolide, octreotide, and oxytocin. His group has also designed cyclopeptides containing heterocyclic structures (imidazole, thiazole, oxazole) intended to serve as potential anticancer agents. His book "Peptide Chemistry in Persian" was recognized as a winner of the Iran Book of the Year Award in 1399 (2020).
Symptoms of ethanol overdose may include nausea, vomiting, CNS depression, coma, acute respiratory failure, or death. Levels of even less than 0.1% can cause intoxication, with unconsciousness often occurring at 0.3–0.4%. Death from ethanol consumption is possible when blood alcohol levels reach 0.4%. A blood level of 0.5% or more is commonly fatal. The oral median lethal dose (LD50) of ethanol in rats is 5,628 mg/kg. Directly translated to human beings, this would mean that if a person who weighs 70 kg (150 lb) drank a 500 mL (17 US fl oz) glass of pure ethanol, they would have an estimated 50% risk of dying. The highest blood alcohol level ever recorded, in which the subject survived, is 1.41%.
Peukert stated "the conquest of the world by a secularized, scientific rationality was so overwhelming, that the switch from religion to science as the main source of a meaning-creating mythology for everyday life took place almost without resistance. The result, however, was that science took upon itself a burden of responsibility that it would soon find a heavy one". Peukert wrote science could not offer spiritual consolation as in a world dominated by science the question of "how can the rationalist, secular ideal of the greatest happiness of the greatest number be vindicated, given that it is rebutted in the case of each individual by illness, suffering and death?", which was impossible to answer. As such, scientists came to be concerned with the body of the individual as a way of determining if that individual should be allowed to pass on his/her genes to the next generation with the criterion being whatever the individual was of "value" or not. In this way, there was a shift from the individual as the center of medical concern to the collective of the volkskörper (the "body" of the entire race).
This referendum included a choice of different terms for a merger with Malaysia and had no option for avoiding merger altogether. On 16 September 1963, Singapore joined with Malaya, the North Borneo, and Sarawak to form the new Federation of Malaysia under the terms of the Malaysia Agreement. Under this Agreement, Singapore had a relatively high level of autonomy compared to the other states of Malaysia. Indonesia opposed the formation of Malaysia due to its own claims over Borneo and launched Konfrontasi in response to the formation of Malaysia. On 10 March 1965, a bomb planted by Indonesian saboteurs on a mezzanine floor of MacDonald House exploded, killing three people and injuring 33 others. It was the deadliest of at least 42 bomb incidents which occurred during the Konfrontasi. Two members of the Indonesian Marine Corps, Osman bin Haji Mohamed Ali and Harun bin Said, were eventually convicted and executed for the crime. The explosion caused US$250,000 (equivalent to US$2,554,118 in 2025) in damages to MacDonald House. Even after the merger, the Singaporean government and the Malaysian central government disagreed on many political and economic issues. Despite an agreement to establish a common market, Singapore continued to face restrictions when trading with the rest of Malaysia. In retaliation, Singapore did not extend to Sabah and Sarawak the full extent of the loans agreed to for economic development of the two eastern states. Talks soon broke down, and abusive speeches and writing became rife on both sides.
== History == Paliperidone palmitate was first approved by the United States Food and Drug Administration (FDA) on July 31, 2009, under the brand name Invega Sustenna, for the acute and maintenance treatment of schizophrenia in adults. Health Canada followed on June 30, 2010, issuing a Notice of Compliance for the same indication. Australia's Therapeutic Goods Administration registered the product on July 28, 2010. The European Medicines Agency (EMA) authorized the once‑monthly injection under the brand name Xeplion on March 4, 2011. In China, the drug was approved in January 2012 and launched later that year under the brand name Shansida (善思达); marketed by Xian-Janssen Pharmaceutical Limited (which is the Janssen (Johnson & Johnson) subsidiary in China), it was the first once-monthly long-acting injectable atypical antipsychotic available in the country. The approval was based on a multi-center clinical trial funded by Xian-Janssen Pharmaceutical Ltd. which demonstrated that Shansida monotherapy was non-inferior to a combination of oral risperidone and long-acting injectable risperidone microspheres (brand name Risperdal Consta) for acute schizophrenia. In Japan, the once‑monthly injection was approved in September 2013 under the brand name Xeplion (ゼプリオン, Zepurion) and was launched on November 19, 2013. Globally, the paliperidone palmitate long-acting injectable market was valued at approximately US$4.1 billion in 2024 and is projected to reach US$6.3 billion by 2031.
Sources: en.wikipedia.org
== Commercial performance == In the United States, the album debuted at #4 on the Billboard 200 chart behind Travis Scott's JackBoys 2 and Justin Bieber's Swag with 118,000 album-equivalent units, matching the debut of Lord Willin' (2002) and simultaneously marking the duo's second ever top-10 album. Of those 118,000 album-equivalent units, 58,000 were pure album sales and 59,000 were from streaming services, marking Clipse's biggest streaming week ever with 77.49 million on-demand streams of the album's tracks. Elsewhere, the album debuted at #1 on the Billboard Independent Albums chart, and charted top-10 placements in Switzerland and Canada.
The first β-sheet structure was proposed by William Astbury in the 1930s. He proposed the idea of hydrogen bonding between the peptide bonds of parallel or antiparallel extended β-strands. However, Astbury did not have the necessary data on the bond geometry of the amino acids in order to build accurate models, especially since he did not then know that the peptide bond was planar. A refined version was proposed by Linus Pauling and Robert Corey in 1951. Their model incorporated the planarity of the peptide bond which they previously explained as resulting from keto-enol tautomerization.
TNP refers to the chemical compound 2,4,6-trinitrophenol, also known as Picric acid. It is a primary constituent of many unexploded landmines, and is a cousin to TNT, but less stable. It is recognized as an environmental contaminant and is toxic to many organisms. It is still commonly used in the manufacturing of fireworks, explosives, and rocket fuels, as well as in leather, pharmaceutical, and dye industries. ATP is an essential mediator of life. It is used to overcome unfavorable energy barriers to initiate and fuel chemical reactions. It is also used to drive biological machinery and regulate a number of processes via protein-phosphorylation. However, the proteins that bind ATP for both regulation and enzymatic reactions are very diverse—many yet undiscovered—and for many proteins their relationship to ATP in terms of number of binding sites, binding constants, and dissociation constants remain unclear.
== Rubidium-87 == Rubidium-87 is one of two natural isotopes of rubidium, with an abundance of 27.835%, and a half-life of 4.97×1010 years, with beta decay to strontium-87, a stable isotope. During fractional crystallization of igneous rock, Sr tends to become concentrated in plagioclase, leaving Rb in the liquid phase. Hence, the Rb/Sr ratio in residual magma may increase over time, resulting in rocks with increasing Rb/Sr ratios with increasing differentiation. The highest ratios (10 or higher) occur in pegmatites. The age of a mineral, if it has not been subsequently altered, is determined by the parent and daughter abundances, the half-life, and the original content of the daughter, here strontium; the 87Sr/86Sr ratio helps in its calculation. See rubidium-strontium dating for further detail. Rubidium-87 was the first and the most popular atom for making Bose–Einstein condensates in dilute atomic gases. Even though rubidium-85 is more abundant, rubidium-87 has a positive scattering length, which means it is mutually repulsive, at low temperatures. This prevents a collapse of all but the smallest condensates. It is also easy to evaporatively cool, with a consistent strong mutual scattering. There is also a strong supply of cheap uncoated diode lasers typically used in CD writers, which can operate at the correct wavelength.
== Commercialization == As of 2014, Suglat was the top reimbursed drug in Japan. Peak sales reached US$515 million with 800,000 and the cost per patient reached US$644 per year. In 2014, the market for selective SGLT2 inhibitors in Japan was around 9 billion yen. Suglat's share of this market was around 49%. In 2015, sales of Suglat grew 77.8% to 7.3 billion yen, following the availability of long-term prescriptions from May 2015. Suglat's share of the market for selective SGLT2 inhibitors in Japan was around 39%. The projected sales in 2016 is to jump all the way to 12.5 billion yen.
Sources: en.wikipedia.org
Residual moisture can influence chemical degradation, cake collapse, and long-term stability. Low moisture levels usually improve stability, but each product has an optimal range.
Most lyophilized products are stored upright at controlled temperatures, often refrigerated or frozen. Protection from moisture and light helps maintain the dried cake.
A diluent is added to the dried cake, which dissolves to form a solution or suspension. Gentle mixing avoids foaming and preserves sensitive molecules.
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.