A practical reference on Primary drying: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-02-05. Anything still debated is marked as such rather than presented as settled.
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.
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.
Storage conditions depend on the formulation and the intended shelf life. Many pharmaceutical and biological freeze-dried products are kept at 2–8 °C, while some stable foods and reagents tolerate room temperature. Others require −20 °C or colder to slow chemical degradation or aggregation. Protection from light and oxygen is common because oxidation can continue in the dry state. Stability studies usually monitor potency, appearance, moisture, and reconstitution time over months or years. Predictions from accelerated studies are useful but may not fully capture real-time changes.
Quality control for freeze-dried lots combines visual inspection with instrumental tests. Cake appearance, color, and shrinkage are recorded against a reference, while residual moisture is measured by Karl Fischer titration or loss on drying. Thermal analysis can reveal phase transitions and crystallization events, and X-ray diffraction distinguishes amorphous from crystalline solids. Microbiological tests and container closure integrity checks are also routine for sterile products. Analytical methods must be validated for the matrix, because excipients and low moisture can affect accuracy. Open questions include how best to predict long-term stability from short-term data.
| Property | Value | Notes |
|---|---|---|
| Common synonym | Freeze-drying | Same dehydration operation |
| Typical vacuum | 10-100 Pa | Pressure during primary drying |
| Primary drying temperature | -40 to -10 °C | Below collapse temperature for many formulations |
| Cycle duration | 12-72 hours | Varies with load, container, and formulation |
| Key phase change | Sublimation | Solid ice to water vapor |
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.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
Lyophilized products are typically stored as sealed solids in vials or syringes. Moisture ingress is a major concern because many dried cakes are hygroscopic and can lose stability when exposed to humid air. Storage temperature depends on the formulation; some products are kept refrigerated, while others are stable at room temperature. Container closure integrity and headspace moisture are often monitored. Light protection may also be required for some photosensitive materials.
One CMT called COL-3 or metastat has been demonstrated to be a potent MMP inhibitor. COL-3 features a tetracycline scaffold that is unsubstituted on positions C4–C9. Advantages of CMT over conventional tetracyclines are that chronic use does not result in gastrointestinal toxicity and higher plasma levels can be achieved for extended time span reducing administration frequency. The pharmacokinetics of COL-3 has been studied in rats. COL-3 is absorbed slowly from the gastrointestinal tract. 3% are excreted through the urinary tract while 55–66% is excreted in feces. The drug is highly lipophilic and able to cross the blood brain barrier at higher doses. COL-3 accumulates in higher concentration in heart tissue and testis. In clinical trials plasma protein binding has been shown to be high (~94,5%). Most COL-3 binds to serum albumin.
This is the largest division of the Society. It marked its 100th anniversary in 2008. The first Chair of the Division was Edward Curtis Franklin. The Organic Division played a part in establishing Organic Syntheses, Inc. and Organic Reactions, Inc. and it maintains close ties to both organizations. The Division's best known activities include organizing symposia (talks and poster sessions) at the biannual ACS National Meetings, for the purpose of recognizing promising Assistant Professors, talented young researchers, outstanding technical contributions from junior-level chemists, in the field of organic chemistry. The symposia also honor national award winners, including the Arthur C. Cope Award, Cope Scholar Award, James Flack Norris Award in Physical Organic Chemistry, Herbert C. Brown Award for Creative Research in Synthetic Methods. The Division helps to organize symposia at the international meeting called Pacifichem and it organizes the biennial National Organic Chemistry Symposium (NOS) which highlights recent advances in organic chemistry and hosts the Roger Adams Award address. The Division also organizes corporate sponsorships to provide fellowships for PhD students and undergraduates. It also organizes the Graduate Research Symposium and manages award and travel grant programs for undergraduates.
The GRP RNA motif is a conserved RNA structural element identified in introns of glycine-rich RNA-binding protein genes, including GRP7 and GRP8. It is associated with alternative splicing and nonsense-mediated decay (NMD). GRP RNA motif has been reported as a cis-regulatory element, that modulates binding of GRP7 and GRP8 proteins to their RNA targets. The motif is predicted to form a stem-loop structure of approximately 20 base pairs. An alternative 5′ splice site is located near the base of the stem, suggesting that RNA structure may influence splice-site accessibility. In Arabidopsis thaliana (At), AtGRP7 and AtGRP8 are circadian clock-regulated RNA-binding proteins that form an interlocked auto-regulatory and cross-regulatory feedback network based on alternative splicing and NMD of their own pre-mRNAs, contributing to circadian output regulation, were transcript levels oscillate with a daily rhythm. GRP7 and GRP8 are also involved in regulating flowering time. Homologous motifs of GRP RNA motif have been identified in multiple plant species within the Pentapetalae clade.
VR offers several novel control schemes - how the player manipulates their in-game character through the game world and the direction they are looking - compared to the traditional free look or mouselook offered by the traditional KBM or standard controller. Movement and aim may be coupled between the headset and the controllers or may be decoupled, typically with the headset controlling the direction of movement and controller the aim, which generally leads to more immersive experiences. Some VR systems such as the HTC Vive and Oculus offer room scale tracking, which not only incorporate the motions of the player but where they are physically located within a given area and the physical positioning of their body. This allows the player to move around the area as part of the VR experience. Games usually make this an optional experience since not all VR systems support it, and not all players have space to be able to move about. Example of games that support room scale tracking include Job Simulator and Rec Room. When room scale is not available, alternate movement schemes have been developed when character movement is required. A player may be moved automatically by the game as necessary, a player may need to look at a target location and indicate through a control scheme their desire to move their character to that spot, or the player may use more traditional controls such as an analog stick or keyboard presses to move their character.
Sources: en.wikipedia.org
==== Korea ==== The earliest soy sauce brewing in Korea seems to have begun in the era of the Three Kingdoms. Jangdoks used for soy sauce brewing are found in the mural paintings of Anak Tomb No. 3 from the 4th century Goguryeo. In Samguk sagi, a historical record of the Three Kingdoms era, it is written that ganjang (soy sauce) and doenjang (soybean paste), along with meju (soybean block) and jeotgal (salted seafood), were prepared for the wedding ceremony of the King Sinmun in February 683. Sikhwaji, a section from Goryeosa (History of Goryeo), recorded that ganjang and doenjang were included in the relief supplies in 1018, after a Khitan invasion, and in 1052, when a famine occurred. Joseon texts such as Guhwangchwaryo and Jeungbo sallim gyeongje contain the detailed procedures on how to brew good quality ganjang and doenjang. Gyuhap chongseo explains how to pick a date for brewing, what to forbear, and how to keep and preserve ganjang and doenjang.
== National Mass Spectrometry Service == A grant of £670,000 was awarded in 1985 by the then Science and Engineering Research Council (SERC) to establish a national Mass Spectrometry Center at Swansea University to provide an analytical service to British Universities. It was officially opened in April 1987 by Lord Callaghan. In 2002, the center was enlarged and the new laboratories were opened by Lord Morgan. Following successful £3,000,000 contract renewal Edwina Hart, the Minister for Economy, Science and Transport, officially re-opened the EPSRC National Research Facility after refurbishment in 2015.
See the Bombers fly up, up! To win the premiership flag. Our boys who play this grand old game, Are always striving for glory and fame! See the Bombers fly up, up, The other teams they don't fear; They all try their best, But they can't get near, As the Bombers fly up! Songwriter Mike Brady, of "Up There Cazaly" fame, penned an updated version of the song in 1999 complete with a new verse arrangement, but it was not well received. However, this version is occasionally played at club functions. In 2018, Andrews revealed that there was an error in the lyrics, in which in the line "The other teams they don't fear", the word "they" was supposed to be "we".
Alcohol (ethanol/ethyl alcohol) – GABAA receptor positive allosteric modulator Alkyl nitrites (poppers) (e.g., amyl nitrite) – nitric oxide donors, vasodilators, muscle relaxants, inhalants Cannabinoids (e.g., THC, cannabis, synthetic cannabinoids) – cannabinoid CB1 receptor agonists Dissociative hallucinogens (e.g., ketamine, methoxetamine, phencyclidine (PCP)) – ionotropic glutamate NMDA receptor antagonists Entactogens (empathogens) (e.g., MDMA (ecstasy), mephedrone, 6-APB, borax combo) – serotonin–norepinephrine–dopamine releasing agents (SNDRAs), other actions γ-Hydroxybutyric acid (GHB; oxybate) and prodrugs (e.g., GBL, 1,4-BD) – GABAB and GHB receptor agonists Phosphodiesterase PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) Psychostimulants (stimulants) (e.g., amphetamine, methamphetamine, cocaine, mephedrone (4-MMC), metaphedrone (3-MMC), MDPV) – norepinephrine–dopamine releasing agents (NDRAs) and/or norepinephrine–dopamine reuptake inhibitors (NDRIs) Serotonergic psychedelics (e.g., 2C-B, 5-MeO-DiPT, 5-MeO-MiPT) – serotonin 5-HT2A receptor agonists
== Deficiency == There are two major pathways of deficiency of CoQ10 in humans: reduced biosynthesis, and increased use by the body. Biosynthesis is the major source of CoQ10. Biosynthesis requires at least 15 genes, and mutations in any of them can cause CoQ deficiency. CoQ10 levels also may be affected by other genetic defects (such as mutations of mitochondrial DNA, ETFDH, APTX, FXN, and BRAF, genes that are not directly related to the CoQ10 biosynthetic process). Some of these, such as mutations in COQ6, can lead to serious diseases such as steroid-resistant nephrotic syndrome with sensorineural deafness.
Sources: en.wikipedia.org
Primary drying removes ice by sublimation under vacuum. Secondary drying removes water that is bound to the material, often by warming the product after most ice has left. Both stages occur below temperatures that would cause unwanted melting.
Sublimation requires the solvent to remain solid so vapor leaves without passing through a liquid phase. If the product melts, the porous structure can collapse and drying becomes uneven. Maintaining frozen conditions preserves the intended physical form.
No, freeze-drying is a dehydration method, not a sterilization step. It can reduce water activity and limit microbial growth during storage, but it does not reliably kill microbes or remove endotoxins. Sterility must come from separate validated processes.
Karl Fischer titration is widely used because it is specific for water and works at low levels. Loss on drying is simpler but less specific, since volatile solvents or decomposition products can also be lost.