This is a working overview of Primary drying, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-10-24. Anything still debated is marked as such rather than presented as settled.
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.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
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.
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and fixes the structure of the sample. After freezing, primary drying lowers pressure so ice changes directly to vapor without passing through a liquid phase. Secondary drying then removes bound water that remains after ice sublimation. The result is a dry, porous solid that often retains its original shape.
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.
Osmium (76Os) has seven naturally occurring isotopes, five of which are stable: 187Os, 188Os, 189Os, 190Os, and (most abundant) 192Os. The other natural isotopes, 184Os and 186Os, have extremely long half-lives (1.12×1013 years and 2.0×1015 years, respectively) and for practical purposes can be considered to be stable as well. 187Os is the daughter of 187Re (half-life 4.12×1010 years) and is most often measured by the 187Os/188Os ratio. This ratio, as well as the 187Re/188Os ratio, have been used extensively in dating terrestrial as well as meteoric rocks. It has also been used to measure the intensity of continental weathering over geologic time and to fix minimum ages for stabilization of the mantle roots of continental cratons. There are also 31 artificial radioisotopes, the longest-lived of which are 194Os with a half-life of 6.0 years, 185Os with 92.95 days, and 191Os with 14.99 days; others are under 30 hours, with most under seven minutes. There are also 19 listed nuclear isomers, the longest-lived of which is 191mOs with a half-life of 13.10 hours. All isotopes and nuclear isomers of osmium are either radioactive or observationally stable, meaning that they are predicted to be radioactive but no actual decay has been observed.
On 2 May, a report accompanied by an open letter concludes that Alphabet Inc, against its voluntary promises, still runs climate misinformation ads. Statements by Elon Musk in 2022 suggest YouTube may also show ethically disputed advertising other than science-related misinformation such as extensively showing "scam ads". 25 May 5,000 marine species new to science are discovered in the Clipperton fracture zone, a proposed deep sea mining hotspot in the Pacific Ocean. Explainable deep learning is used to develop an experimental antibiotic called abaucin, which is shown to be effective against A. baumannii. Evidence for the existence of a second Kuiper Belt is presented by NASA scientists, which the New Horizons spacecraft could potentially visit during the late 2020s or early 2030s. A study reports observational evidence for problematic fast slowdown of the Antarctic bottom water current. Neuroengineers demonstrate induction of a torpor-like state in mice via ultrasound stimulation. 29 May A new record high efficiency of 19.3% for organic solar cells is reported. MBR Explorer is announced by the United Arab Emirates Space Agency, an uncrewed mission to explore seven asteroids, which includes an attempted surface landing on 269 Justitia in 2034. Scientists provide details of H5N1 bird flu's fast viral evolution of clade 2.3.4.4b including reassortment after "explosive geographic expansion in 2021 among wild birds", with relevance to measures such as existing candidate vaccines. 31 May The first X-ray of a single atom is reported.
The climate of Ghana is tropical, and there is wet season and dry season. Ghana sits at the intersection of three hydro-climatic zones. The eastern coastal belt is warm and comparatively dry, the south-west corner of Ghana is hot and humid, and the north of Ghana is hot and dry. Climate change in Ghana has impacts on the people of Ghana. Increasing temperatures and changes in rainfall, extreme weather, drought, wild fires, floods and sea-level rise are expected to negatively affect the country's infrastructure, hydropower production, food security, water supply, and coastal and agricultural livelihoods such as farming and fisheries. Ghana's economy will be impacted by climate change, due to its dependence on climate-sensitive sectors such as agriculture, energy, and forestry. Diseases like malaria, dengue fever and cholera are predicted to increase due to changes in water conditions. Ghana signed the Paris Agreement in 2016. It aims to avoid 64 million metric tons of greenhouse gas emissions by 2030, compared to a business-as-usual scenario for 2020–2030. Ghana has committed to net zero by 2060.
=== Spread === E. floccosum can remain viable for long periods of time by producing arthroconidia in skin scales. Arthroconidia are thick-walled spores with higher resistance to drying and heat conditions than mycelium. Arthroconidia formation allows E. floccosum to survive for years in showers, baths, swimming pools, towels, blankets, sheets, shoes and other clothing. The fungus commonly spreads by contact in showers and gym facilities.
Sources: en.wikipedia.org
== Cancer resistance to immunotherapy == While immunotherapy has provided a tool for combating cancer, a significant clinical challenge comes with it. Cancer cells can develop resistance to immunotherapy treatment, which decreases the efficacy of the treatment. A substantial proportion of patients either begin treatment with resistance, causing failure in response, or develop resistance after the medication is administered. A recent review estimated that a majority of patients with solid tumors eventually acquire resistance to immunotherapy. Resistance to immunotherapy falls under either the category of primary or innate resistance, which causes a lack of response to immunotherapy treatment from the get-go, or acquired resistance, where there is an initial positive response to treatment followed by regression. Resistance arises through mechanisms that alter the interaction between tumor cells, the immune system, and the tumor microenvironment. Tumor antigenicity, or the ability for the immune system to recognize cancer cells, is a primary target for resistance. Resistance mutations that down-regulate (decrease) the expression of antigen-presenting factors allow the immune system to ignore the presence of cancer cells. The major histocompatibility complex (MHC), which presents antigens on the cell surface to prompt immune recognition, is often a target. When T cells can no longer identify malignant cells, this renders therapies and immune recognition useless. A second mechanism of immunotherapy resistance is impaired immune cell function.
=== Artificial intelligence === Artificial intelligences (and to a lesser degree, the non-sentient computers omnipresent in all material goods), form the backbone of the technological advances of the Culture. Not only are they the most advanced scientists and designers the Culture has, their lesser functions also oversee the vast (but usually hidden) production and maintenance capabilities of the society. The Culture has achieved artificial intelligences where each Mind has thought processing capabilities many orders of magnitude beyond that of human beings, and data storage drives which, if written out on paper and stored in filing cabinets, would cover thousands of planets skyscraper high (as described by one Mind in Consider Phlebas). Yet it has managed to condense these entities to a volume of several dozen cubic metres (though much of the contents and the operating structure are continually in hyperspace). Minds also demonstrate reaction times and multitasking abilities orders of magnitude greater than any sentient being; armed engagements between Culture and equivalent technological civilisations sometimes occur in timeframes as short as microseconds, and standard Orbital Minds are capable of running all of the vital systems on the Orbital while simultaneously conversing with millions of the inhabitants and observing phenomena in the surrounding regions of space.
== Treatment == The treatment of burn scar contracture and deformity begins upon hospitalization. Wound care and functional outcomes can be predicted from the initial assessment of wound depth and location. Epidermal and partial thickness wounds heal in 1 to 3 weeks through epithelial migration from the wound edges and epithelial budding from the appendages of the sweat and hair glands. These wounds pose only a small risk of contracture and hypertrophic scarring. Full-thickness (FT) injuries cause dermal wound healing, which is characterized by maturation (contraction and increased tensile strength), proliferation (collagen synthesis leading to wound closure), and inflammation (edema). FT wounds heal by excision and grafting, contracture, or epithelial ingrowths from the margins. Because of insufficient tissue length and extensibility, severe damage to the integument system may result in significant impairment and disability. By using stress-strain curves, where stress is equal to force and strain is equal to tissue elongation, mechanical engineering principles can be used to assess the biomechanics of skin and scars. Stretching an adult burn scar is similar to stretching a tendon in terms of elasticity. On the other hand, persistent force applied to tissue will cause it to elongate, which will lead to a plastic change in length and an increase in range of motion. Fast and forceful stress is much less effective than a gentle, prolonged stretch that the patient can tolerate.
In nuclear physics, the island of stability is a predicted set of isotopes of superheavy elements that may have considerably longer half-lives than known isotopes of these elements. It is predicted to appear as an "island" in the chart of nuclides, separated from known stable and long-lived primordial radionuclides. Its theoretical existence is attributed to stabilizing effects of predicted "magic numbers" of protons and neutrons in the superheavy mass region.
Eosin is most often used as a counterstain to hematoxylin in H&E (haematoxylin and eosin) staining. H&E staining is one of the most commonly used techniques in histology. Tissue stained with haematoxylin and eosin shows cytoplasm stained pink-orange and nuclei stained darkly, either blue or purple. Eosin also stains red blood cells intensely red. For staining, eosin Y is typically used in concentrations of 1 to 5 percent weight by volume, dissolved in water or ethanol. For prevention of mold growth in aqueous solutions, thymol is sometimes added. A small concentration (0.5 percent) of acetic acid usually gives a deeper red stain to the tissue. It is listed as an IARC class 3 carcinogen (safe).
Sources: en.wikipedia.org
Although the dissolution of the Soviet Union ended the Cold War in 1991 and greatly reduced the political tensions between the United States and Russia, the Soviet Union's formal successor state, both countries remained in a "nuclear stand-off" due to the continuing presence of a very large number of deliverable nuclear warheads on both sides. Additionally, the end of the Cold War led the United States to become increasingly concerned with the development of nuclear technology by other nations outside of the former Soviet Union. In 1995, a branch of the U.S. Strategic Command produced an outline of forward-thinking strategies in the document "Essentials of Post–Cold War Deterrence". In 1995, a Black Brant sounding rocket launched from the Andøya Space Center caused a high alert in Russia, known as the Norwegian Rocket Incident. The Russians thought it might be a nuclear missile launched from an American submarine. In 1996, a Russian continuity of government facility, Kosvinsky Mountain, which is believed to be a counterpart to the US Cheyenne Mountain Complex, was completed. It was designed to resist US earth-penetrating nuclear warheads, and is believed to host the Russian Strategic Rocket Forces alternate command post, a post for the general staff built to compensate for the vulnerability of older Soviet era command posts in the Moscow region. In spite of this, the primary command posts for the Strategic Rocket Forces remains Kuntsevo in Moscow and the secondary is the Kosvinsky Mountain in the Ural Mountains.
== Regulations == In 1961 phenoperidine was added to the 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs by the World Health Organization via the Single Convention on Narcotic Drugs. In the US it is classified as a Drug Enforcement Administration (DEA) Schedule I controlled substance opiate with a corresponding code 9641.
Radiation therapy is usually reserved for people who have tumours remaining after surgery. These people often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. People monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.
ADIME, or Assessment, Diagnosis, Intervention, and Monitoring/Evaluation, is a process used to ensure high quality nutrition care to patients and clients from nutrition professionals, such as Registered Dietitians (RD) or Registered Dietitian Nutritionist (RDN). ADIME is used as a means of charting patient progress and to encourage a universal language amongst nutrition professionals. The ADIME process consists of four steps:
Side effects of midazolam in the elderly are listed above. People experiencing amnesia as a side effect of midazolam are generally unaware their memory is impaired, unless they had previously known it as a side effect. Long-term use of benzodiazepines has been associated with long-lasting deficits in memory, and show only partial recovery six months after stopping benzodiazepines. It is unclear whether full recovery occurs after longer periods of abstinence. Benzodiazepines can cause or worsen depression. Paradoxical excitement occasionally occurs with benzodiazepines, including a worsening of seizures. Children and elderly individuals or those with a history of excessive alcohol use and individuals with a history of aggressive behavior or anger are at increased risk of paradoxical effects. Paradoxical reactions are particularly associated with intravenous administration. After nighttime administration of midazolam, residual 'hangover' effects, such as sleepiness and impaired psychomotor and cognitive functions, may persist into the next day. This may impair the ability of users to drive safely and may increase the risk of falls and hip fractures. Sedation, respiratory depression and hypotension due to a reduction in systematic vascular resistance, and an increase in heart rate can occur. If intravenous midazolam is given too quickly, hypotension may occur. A "midazolam infusion syndrome" may result from high doses, is characterised by delayed arousal hours to days after discontinuation of midazolam, and may lead to an increase in the length of ventilatory support needed.
Sources: en.wikipedia.org
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.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
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.