Everything below concerns secondary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-04-19. Numbers and descriptions here follow the published literature rather than marketing material.
Formulation composition influences whether freeze-drying produces an intact cake or a collapsed mass. Excipients such as sugars and polymers can raise the collapse temperature and provide bulk during drying. The critical temperature for primary drying is often the collapse temperature or the glass transition temperature of the maximally concentrated phase. If the product temperature exceeds this threshold, the frozen matrix may soften and lose structure. Established practice therefore links shelf temperature and chamber pressure to the formulation's thermal properties.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common name | Freeze-drying | Process removes water by sublimation under vacuum. |
| Typical primary drying shelf temperature | -40 C to -10 C | Set below the formulation's collapse temperature. |
| Typical chamber pressure | 0.05-0.3 mbar | Low pressure allows ice to sublime below its triple point. |
| Water content after drying | 0.5-3% by weight | Higher values may reduce storage stability for some materials. |
| Key thermal parameter | Collapse temperature | Measured by freeze-drying microscopy or differential scanning calorimetry. |
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.
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 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.
Afropop Worldwide's public radio program on Zulu Music, "The Zulu Factor" People of Africa, Zulu marriage explained An article on Piet Retief, including his interactions with Dingane History section of the official page for the Zululand region Archived 26 September 2008 at the Wayback Machine Human Rights Watch report on KwaZulu, just before the 1994 elections – This includes detailed, well-referenced, sections on recent Zulu history.
This can be avoided by breathing air into the mask through the nose. Goggles covering only the eyes are not suitable for deep diving as they cannot be equalised. Dry suit squeeze. The main risk is skin getting pinched and bruised by folds of the dry suit when squeezed on descent. Most dry suits can be equalised against squeeze via a manually operated valve fed from a low pressure gas supply. Air must be manually injected during the descent to avoid squeeze and is manually or automatically vented on the ascent to maintain buoyancy control. Diving helmet squeeze: Helmet squeeze will occur if the gas supply hose is severed above the diver and the non-return valve at the helmet gas inlet fails or is not fitted. Severity will depend on the hydrostatic pressure difference. A very rapid descent, usually by accident, may exceed the rate at which the breathing gas supply can equalise the pressure causing a temporary squeeze. The introduction of the non-return valve and high maximum gas supply flow rates have all but eliminated both these risks. In helmets fitted with a neck dam, the dam will admit water into the helmet if the internal pressure gets too low; this is less of a problem than helmet squeeze but the diver may drown if the gas supply is not reinstated quickly. This form of barotrauma is avoidable by controlled descent rate, which is standard practice for commercial divers, who will use shotlines, diving stages and wet bells to control descent and ascent rates.
=== Centipawn: Chess position === Chess software frequently uses centipawns internally or externally as a unit measuring how strong each player's situation position is, and hence also by how much one player is beating the other, and how strong a possible move is. 100 centipawns = the value of 1 pawn – more specifically, something like the average value of the pawns at the start of the game, as the actual value of pawns depends on their position. Loss of a pawn will therefore typically lose that player 100 centipawns. The centipawn is often used for comparing possible moves, as in a given position, chess software will often rate the better of two moves within a few centipawns of each other.
=== Cultural === Cultural attitudes towards body image, beauty, and health also significantly impact the incidence of anorexia nervosa. There is a stark contrast between Western societies that idolize slimness and certain Eastern traditions that worship gods depicted with larger bodies, and these varying cultural norms have varying influences on eating behaviors, self-perception, and anorexia in their respective cultures. For example, despite the fact that "fat phobia", or a fear of fat, is a key diagnostic criteria of anorexia by the DSM-5, anorexic patients in Asia rarely display this trait, as deep-rooted cultural values in Asian cultures praise larger bodies. Fat phobia appears to be intricately linked to Western culture, encompassing how various cultural perceptions impact anorexia in various ways. It calls on the need for greater, diverse cultural consideration when looking at the diagnosis and experience of anorexia. For instance, in a cross-sectional study done on British South Asian adolescent English adolescent anorexia patients, it was found that both patients' symptom profiles differed. South Asians were less likely to exhibit fat-phobia as a symptom versus their English counterparts, instead exhibiting loss of appetite. Patients usually attributed their restricted food intake to somatic symptoms such as bloating, stomach pain, or lack of appetite. However, both kinds of patients had distorted body images, implying the possibility of disordered eating and highlighting the need for cultural sensitivity when diagnosing anorexia.
He responded, "Not even a little bit. The only thing that matters when I’m talking about Iran — they can't have a nuclear weapon. I don’t think about Americans’ financial situation. I don't think about anybody. I think about one thing — we cannot let Iran have a nuclear weapon. That's all." He later told Fox News in an interview regarding his previous statement, "That's a perfect statement. I'd make it again." On 25 May, Trump said that any peace agreement with Iran must be tied to the Abraham Accords, stating that it "should be mandatory" for Saudi Arabia, Qatar, and Pakistan to establish diplomatic ties with Israel, in addition to Egypt, Jordan, and Turkey, which already have ties with Israel. On 1 June, following the shutdown of further talks by Iran due to planned Israeli attacks on Beirut, he told CNBC that he did not care and claimed that the negotiation process "started to get very boring". Later the same day, he claimed to have a "very productive call" with Netanyahu and Hezbollah to pause attacks on each other and reenable US talks with Iran.
Sources: en.wikipedia.org
=== Pharmacokinetics === Detailed pharmacokinetic studies on arsenic trioxide have not been conducted. When administered intravenously, a steady state is reached after 8–10 days. Arsenic binds to proteins to an insignificant extent. The highest concentrations of arsenic are found in the liver, kidneys, heart, lungs, hair, and nails. Arsenous acid is oxidized to arsenic acid and methylated in the liver, and then excreted 60% in the urine. The drug has a half-life of 92 hours. Arsenic trioxide is neither a substrate nor an inhibitor of cytochrome P450 isozymes (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, 4A9/11).
== Research == Pseudoephedrine has been studied in the treatment of snoring. However, data are inadequate to support this use. A study has found that pseudoephedrine can reduce milk production in breastfeeding women. This might have been due to suppression of prolactin secretion. Pseudoephedrine might be useful for lactation suppression.
CPC Scientific Group was founded in 2001, and the US company established in 2005 by Shawn Lee, Ph.D., and began by supplying research-grade custom peptides, catalog peptides, and Fmoc-protected amino acids. In 2006, the company opened a GMP (Good Manufacturing Practice) facility in Hangzhou, China to support the production of peptides for clinical use. The Hangzhou site underwent its first inspection by the U.S. Food and Drug Administration (FDA) in 2011, after which CPC Scientific began supplying pharmaceutical-grade peptides to clients in the United States. On March 17, 2016, the company passed a fourth FDA inspection. In 2024, the company completed a fifth U.S. FDA inspection and was also inspected by Australia’s Therapeutic Goods Administration (TGA). In 2025, CPC Scientific obtained ISO 22716:2007 Cosmetic GMP certification for the manufacture of peptide ingredients for cosmetic applications. CPC Scientific is part of Medtide Inc., which was listed on the Main Board of the Hong Kong Stock Exchange on June 30, 2025 (Stock Code: 03880).
The structure of prolactin is similar to that of growth hormone and placental lactogen. The molecule is folded due to the activity of three disulfide bonds. Significant heterogeneity of the molecule has been described, thus bioassays and immunoassays can give different results due to differing glycosylation, phosphorylation and sulfation, as well as degradation. The non-glycosylated form of prolactin is the dominant form that is secreted by the pituitary gland. The three different sizes of prolactin are:
Sources: en.wikipedia.org
Investigators have hypothesized that the PHLPP isoforms may play roles in cancer, for several reasons. First, the genetic loci coding for PHLPP1 and 2 are commonly lost in cancer. The region including PHLPP1, 18q21.33, commonly undergoes loss of heterozygosity (LOH) in colon cancers, while 16q22.3, which includes the PHLPP2 gene, undergoes LOH in breast and ovarian cancers, Wilms tumors, prostate cancer and hepatocellular carcinoma. Second, experimental overexpression of PHLPP in cancer cell lines tends to decrease apoptosis and increase proliferation, and stable colon and glioblastoma cell lines overexpressing PHLPP1 show decreased tumor formation in xenograft models. Recent studies have also shown that Bcr-Abl, the fusion protein responsible for chronic myelogenous leukemia (CML), downregulates PHLPP1 and PHLPP2 levels, and that decreasing PHLPP levels interferes with the efficacy of Bcr-Abl inhibitors, including Gleevec, in CML cell lines. Finally, both Akt and PKC are known to be tumor promoters, suggesting that their negative regulator PHLPP may act as a tumor suppressor.
== Silicon-28 == Silicon-28, the most abundant isotope of silicon, is of particular interest in the construction of quantum computers when highly enriched, as the presence of 29Si in a sample of silicon contributes to quantum decoherence. Extremely pure (>99.9998%) samples of 28Si can be produced through selective ionization and deposition of 28Si from silane gas. Due to the extremely high purity that can be obtained in this manner, the Avogadro project sought to develop a new definition of the kilogram by making a 93.75 mm (3.691 in) sphere of the isotope and determining the exact number of atoms in the sample. Silicon-28 is produced in stars during the alpha process and the oxygen-burning process, and drives the silicon-burning process in massive stars shortly before they go supernova.
== Alternative Medicine == The effect of Ayurvedic treatments has been researched, however due to methodological flaws of relevant studies and research, it has not been possible to draw conclusions regarding efficacy of these treatments and there is insufficient evidence to recommend them.
== 2016 presidential campaign (2015–2016) == In December 2015, Trump's personal physician, Harold Bornstein, released a letter praising Trump for "extraordinary physical strength and stamina". The letter asserted that Trump would be "the healthiest individual ever elected to the presidency" and said that a recent medical exam yielded "only positive results". Before Bornstein's death in 2021, he told CNN that Trump had dictated the entire letter. The language used was in Trump's style and not typical of a medical doctor; in particular, the American journalist Kurt Eichenwald noted that positive test results do not necessarily mean a favorable outcome for the patient. A follow-up medical report by Bornstein claimed that Trump's blood pressure, liver and thyroid functions were within the normal range, and that he takes a statin. At 6 feet 3 inches (191 centimeters) and 236 pounds (107 kilograms), Trump's body mass index of 29.5 registered on the higher end of overweight BMIs. During the 2016 Republican Party presidential primaries, presidential candidate and primary opponent Jeb Bush speculated in February 2016 that Trump had mental health issues, stating, "I'm not a psychiatrist or a psychologist, but the guy needs therapy."
==== Abnormal tongue motion ==== Abnormal tongue motion of infants is commonly caused by nipple confusion. When infants are given a rubber nipple and pacifier, they may sip at the maternal nipple as if it was a rubber nipple. The tongue movements used in breastfeeding and bottle-feeding are different: infants use a wave-like motion to remove breast milk in breastfeeding and thrusting action against the latex nipple to control milk flow in bottle-feeding. If the infant pinches and presses the nipple with the gums repeatedly, it creates a large friction and results in nipple soreness and bruising.
Sources: en.wikipedia.org
Primary drying removes ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, often under the same vacuum. The two stages differ in the water state being removed.
Freezing determines ice crystal size, pore structure, and the concentration of solutes in remaining liquid. Faster freezing generally creates smaller ice crystals and a denser dried matrix. These features affect drying rate and reconstitution behavior.
Lyophilization reduces water content but usually leaves a small amount of water in the dried material. Some water remains bound to solids or trapped in the dried matrix. Very low water targets can require extended secondary drying, which may alter product stability.
Lyophilization removes water by sublimation from a frozen material, while evaporation changes liquid water into vapor. The low-pressure freezing step avoids the liquid phase and can preserve heat-sensitive structures.