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 2025-10-02 and is reviewed periodically as new material appears.
Secondary drying removes bound water that remains after ice sublimation. Shelf temperature is raised gradually while pressure remains low, reducing water content to a target range. Over-drying can cause brittleness or electrostatic issues, while under-drying affects stability. The endpoint is often judged by pressure rise tests, temperature measurements, or water content analysis. Scale-up depends on matching heat and mass transfer across equipment sizes. Small changes in shelf temperature or pressure can alter cycle length substantially.
Lyophilization, or freeze-drying, removes water from a material by freezing it and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intervening liquid state. It is used for heat-sensitive materials that would degrade in conventional drying. The three stages are freezing, primary drying, and secondary drying, each with distinct temperature and pressure requirements. In practice, cycle design balances these variables.
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.
Lyophilized solids are often hygroscopic, so handling occurs in controlled low-humidity areas or glove boxes when the material is exposed. Vials remain sealed with elastomeric stoppers and aluminum crimps until use, because airborne moisture can raise residual water and shorten shelf life. The porous cake is fragile and may crack, shrink, or powder during transport. Personnel typically avoid repeated warming and cooling of sealed units, which can draw moisture through closures. These practices aim to preserve the low water content achieved during drying.
| Property | Value | Notes |
|---|---|---|
| Process name | Lyophilization or freeze-drying | Both terms appear in technical standards and literature. |
| Phase transition | Sublimation | Solid ice becomes vapor without a liquid step. |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product temperature and equipment. |
| Typical product temperature | -40 °C to -10 °C | Measured during primary drying; formulation sets limits. |
| Water content after drying | 0.5-3% w/w | Target varies by material and stability needs. |
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.
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.
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.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and concentrates dissolved solids. Primary drying then lowers chamber pressure so ice changes directly into vapor without passing through a liquid phase. Secondary drying raises the shelf temperature to remove bound water that remains after ice sublimation. The result is a dry, porous structure that can be reconstituted later.
==== Oily ==== Oily chloramphenicol (or chloramphenicol oil suspension) is a long-acting preparation of chloramphenicol first introduced by Roussel in 1954; marketed as Tifomycine, it was originally used as a treatment for typhoid. Roussel stopped production of oily chloramphenicol in 1995; the International Dispensary Association Foundation has manufactured it since 1998, first in Malta and then in India from December 2004. Oily chloramphenicol was first used to treat meningitis in 1975 and numerous studies since have demonstrated its efficacy. It is the cheapest treatment available for meningitis (US$5 per treatment course, compared to US$30 for ampicillin and US$15 for five days of ceftriaxone). It has the great advantage of requiring only a single injection, whereas ceftriaxone is traditionally given daily for five days. This recommendation may yet change, now that a single dose of ceftriaxone (cost US$3) has been shown to be equivalent to one dose of oily chloramphenicol.
== External links == "Relaxin Family Peptide Receptors: RXFP4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-09.
In college basketball, the NCAA Division I men's and women's tournaments will expand to 76 teams beginning next year. The Pentagon releases declassified documents about UFOs and extraterrestrial life. May 10 – Six people are found dead inside a boxcar on a Union Pacific freight train in Laredo, Texas. May 12 2025–2026 United States redistricting: The Republican-led South Carolina Senate rejects redistricting efforts to redraw the congressional districts in South Carolina, including efforts to eliminate the seat represented by congressman Jim Clyburn. American autonomous driving technology company Waymo recalls 3,800 robotaxis over risks that they could enter flooded areas.
As this is a cube, the top and bottom surfaces are identical in shape and area, and the pressure difference between the top and bottom of the cube is directly proportional to the depth difference, and the resultant force difference is exactly equal to the weight of the fluid that would occupy the volume of the cube in its absence. This means that the resultant upward force on the cube is equal to the weight of the fluid that would fit into the volume of the cube, and the downward force on the cube is its weight, in the absence of external forces. This analogy is valid for variations in the size of the cube. If two cubes are placed alongside each other with a face of each in contact, the pressures and resultant forces on the sides or parts thereof in contact are balanced and may be disregarded, as the contact surfaces are equal in shape, size and pressure distribution, therefore the buoyancy of two cubes in contact is the sum of the buoyancies of each cube. This analogy can be extended to an arbitrary number of cubes. An object of any shape can be approximated as a group of cubes in contact with each other, and as the size of the cube is decreased, the precision of the approximation increases. The limiting case for infinitely small cubes is the exact equivalence. Angled surfaces do not nullify the analogy as the resultant force can be split into orthogonal components and each dealt with in the same way.
Sources: en.wikipedia.org
The first reference to Israel in non-biblical sources is found in the Merneptah Stele in c. 1209 BCE. The inscription is very brief and says: "Israel is laid waste and his seed is not". The inscription refers to a people, not an individual or nation state, who inhabit central Palestine or the highlands of Samaria. Some Egyptologists suggest that Israel appeared in earlier topographical reliefs, dating to the Eighteenth Dynasty or Nineteenth Dynasty (i.e. reign of Ramesses II) , but this reading remains controversial. In the Hebrew Bible, Israel first appears in Genesis 32:29, where an angel renames Jacob to Israel after Jacob fought with him. According to the folk etymology given in the text, Israel is derived from yisra, "to prevail over" or "to struggle with", and El, a Canaanite-Mesopotamian creator god that is tenuously identified with Yahweh. However, modern scholarship interprets El as the subject, "El rules/struggles", from sarar (שָׂרַר) 'to rule' (cognate with sar (שַׂר) 'ruler', Akkadian šarru 'ruler, king'), which is likely cognate with the similar root sara (שׂרה) "fought, strove, contended". Dr. Tzemah Yoreh clarifies that Israel is a combination of 'to strive with' (ש.ר.ה) and 'God' (אל) and that Jacob's name alternates between Jacob and Israel in the biblical narrative, even after his renaming, due to the authors having different opinions about Jacob's moral character. The gradual ethnonymic shift from "Israelites" to "Jews", regardless of their descent from Judah is made explicit in the Book of Esther (4th century BCE) of the Tanakh.
== Therapeutic use(s) == When patients with blood cancers (leukemia and lymphoma) receive high dose chemotherapy and radiation therapy to undergo bone marrow transplantation, they usually get severe oral mucositis. Palifermin reduces the incidence and duration of severe oral mucositis by protecting those cells and stimulating the growth of new epithelial cells to build up the mucosal barrier. Palifermin is also being studied in the prevention and treatment of oral mucositis and dysphagia (difficulty swallowing) in other types of cancer.
==== Re-sentencing of death row inmates ==== The amendments of the law also offered a chance for all current death row inmates to have their cases to be reviewed for re-sentencing. Some death row inmates declined to be re-sentenced, including Tang Hai Liang and Foong Chee Peng. The below cases are known cases where death row inmates applied for re-sentencing.
Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis and meiosis. Techniques used include karyotyping, analysis of G-banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH).
This reaction is exploited in native chemical ligation, a protocol for peptide synthesis. In a related reaction, thioesters can be converted into esters. Thioacetate esters can also be cleaved with methanethiol in the presence of stoichiometric base, as illustrated in the preparation of pent-4-yne-1-thiol:
Sources: en.wikipedia.org
=== Regulation === In the United States, drugs containing diphenoxylate combined with atropine salts are classified as Schedule V controlled substances. (Diphenoxylate by itself is a Schedule II controlled substance.) It is on Schedule III of the Single Convention on Narcotic Drugs, only in forms that contain, according to the Yellow List: "not more than 2.5 milligrams of diphenoxylate calculated as base and a quantity of atropine sulfate equivalent to at least 1 per cent of the dose of diphenoxylate".
=== Hyperrelaxinemia === Premature delivery of relaxin is linked to high levels of relaxin in the mother's bloodstream, known as hyperrelaxinemia. This is caused by the impact of relaxin on the cervix, which disrupts the equilibrium in maintaining the structure of cervical connective tissue. Hyperrelaxinemia caused by ovarian stimulation results in an increased rate of the risk of premature labor and preterm birth.
== Building blocks == Supramolecular systems are rarely designed from first principles. Rather, chemists have a range of well-studied structural and functional building blocks that they are able to use to build up larger functional architectures. Many of these exist as whole families of similar units, from which the analog with the exact desired properties can be chosen.
=== Counting methods === In order to quantify the number of substitutions, one may reconstruct the ancestral sequence and record the inferred changes at sites (straight counting – likely to provide an underestimate); fitting the substitution rates at sites into predetermined categories (Bayesian approach; poor for small data sets); and generating an individual substitution rate for each codon (computationally expensive). Given enough data, all three of these approaches will tend to the same result.
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.
Lowering pressure reduces the boiling point of water and allows ice to sublimate at temperatures below freezing. Vacuum also limits convective heat transfer, so heat is usually supplied by shelves or radiation. The pressure must stay below the vapor pressure of ice at the product temperature.
The cycle typically includes freezing, primary drying, and secondary drying. Freezing solidifies water and sets the pore structure; primary drying removes bulk ice; secondary drying removes bound water. Some cycles add annealing or pre-freezing steps.
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.