Everything below concerns primary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-09-11. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback during drying.
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.
Storage conditions for dried products usually aim to exclude moisture and oxygen. Vials are sealed under vacuum or with an inert gas, and stoppers must maintain a barrier during transport. Temperature recommendations vary; some materials remain stable at room temperature, while others need refrigeration or frozen storage. Humidity control is critical because dried cakes can absorb water rapidly once a container is opened. Desiccant packs and moisture-barrier bags add further protection during shipping.
Quality control also examines cake structure, color, and reconstitution behavior. A collapsed or shrunken cake can indicate a thermal excursion during drying. Analytical methods such as X-ray diffraction, differential scanning calorimetry, and near-infrared spectroscopy can detect crystallinity or moisture distribution. Regulatory expectations focus on validated assays and lot-to-lot consistency. Questions remain about how well accelerated stability tests predict long-term behavior for every formulation. Visual inspection remains common but is subjective without trained reviewers and reference images.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilization is the American spelling; lyophilisation is British |
| Primary drying mechanism | Sublimation of ice | Occurs under vacuum below the triple point |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product and equipment |
| Typical shelf temperature during freezing | -40 to -20 °C | Lower temperatures may be used for labile products |
| Resulting product form | Porous cake or powder | Appearance depends on formulation and cycle |
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.
Handling practices aim to prevent moisture ingress and mechanical damage. Vials should remain stoppered and crimped until use, and reconstitution should follow the labeled diluent and volume. Shipping may involve temperature-controlled containers and desiccants, but direct contact between desiccant and product is avoided. Regulatory guidance expects documented storage conditions, excursion assessments, and stability commitments. Open questions remain about how best to predict long-term stability from short accelerated studies for every formulation class.
After lyophilization, the product is usually a porous cake or powder with a large internal surface area. This structure can absorb moisture quickly if exposed to humid air, so vials are sealed under vacuum or an inert gas. Moisture uptake may lower the glass transition temperature of the dried matrix and accelerate chemical or physical degradation. Storage conditions therefore depend on the formulation, container, and intended shelf life. Some products remain stable at room temperature, while others require refrigeration or freezing.
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.
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.
== Progress and status == The project has genetically engineered microorganisms to produce long-acting (glargine) and short-acting (lispro) insulin analogs using standard techniques in biotechnology and according to their December 2018 release the "first major milestone ― the production of insulin at lab scale ― is almost complete". The cost to produce insulin via Open Insulin methods is estimated by the project to be such that "roughly $10,000 should be enough to get a group started with the equipment needed to produce enough insulin for 10,000 people". A more recent estimate (May 2020) by the Open Insulin Foundation states that it will cost $200,000 (one-time price, per patient of $7-$20) for used equipment and up to $1,000,000 (one-time price, per patient of $73) for new equipment. The average price per vial was estimated to be $7 with each patient needing two vials per month.
=== Synthesis === Progesterone is commercially produced by semisynthesis. Two main routes are used: one from yam diosgenin first pioneered by Marker in 1940, and one based on soy phytosterols scaled up in the 1970s. Additional (not necessarily economical) semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in chloroform to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.
== Appearance and properties == Emulsions contain both a dispersed and a continuous phase, with the boundary between the phases called the "interface". Emulsions tend to have a cloudy appearance because the many phase interfaces scatter light as it passes through the emulsion. Emulsions appear white when all light is scattered equally. If the emulsion is dilute enough, higher-frequency (shorter-wavelength) light will be scattered more, and the emulsion will appear bluer – this is called the "Tyndall effect". If the emulsion is concentrated enough, the color will be distorted toward comparatively longer wavelengths, and will appear more yellow. This phenomenon is easily observable when comparing skimmed milk, which contains little fat, to cream, which contains a much higher concentration of milk fat. Two special classes of emulsions – microemulsions and nanoemulsions, with droplet sizes below 100 nm – appear translucent. This property is due to the fact that light waves are scattered by the droplets only if their sizes exceed about one-quarter of the wavelength of the incident light. Since the visible spectrum of light is composed of wavelengths between 390 and 750 nanometers (nm), if the droplet sizes in the emulsion are below about 100 nm, the light can penetrate through the emulsion without being scattered. Due to their similarity in appearance, translucent nanoemulsions and microemulsions are frequently confused.
For the isolation and enumeration of B. cereus, there are two standardized methods by International Organization for Standardization (ISO): ISO 7932 and ISO 21871. Because of B. cereus' ability to produce lecithinase and its inability to ferment mannitol, there are some proper selective media for its isolation and identification such as mannitol-egg yolk-polymyxin (MYP) and polymyxin-pyruvate-egg yolk-mannitol-bromothymol blue agar (PEMBA). B. cereus colonies on MYP have a violet-red background and are surrounded by a zone of egg-yolk precipitate. Below is a list of differential techniques and results that can help to identify B. cereus from other bacteria and Bacillus species.
Sources: en.wikipedia.org
=== Generic names === Mirtazapine is the English and French generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopeia, BANTooltip British Approved Name, DCFTooltip Dénomination Commune Française, and JANTooltip Japanese Accepted Name. Its generic name in Spanish, Italian, and Portuguese is mirtazapina and in German, Turkish and Swedish is mirtazapin.
==== Medicare drug negotiation ==== The law reverses aspects of Medicare's price negotiation program, allowing more drugs to be purchased without negotiation and increasing costs for consumers. The Congressional Budget Office estimated $5 billion in lost savings for the government over ten years.
==== Underage users ==== As with other platforms popular with children, underage users may inadvertently reveal their daily routine and whereabouts, raising concerns of potential misuse by sexual predators. At the time of reporting (2018), TikTok had only two privacy settings, either private or completely public, without any middle ground. Comment sections of "sexy" videos, such as young girls dancing in revealing clothes, were found to contain requests for nude pictures. Despite safety concerns, TikTok began rolling out photo, video, and voice messaging around 2025. As of January 2026, the features are only available in certain regions, including the United States and Canada. In recent years, the US has charged and sentenced sexual predators for illegal activities on TikTok against underage girls. On 22 January 2021, the Italian Data Protection Authority demanded that TikTok temporarily suspend Italian users whose age could not be established. The order came after the death of a 10-year-old Sicilian girl involved in an Internet challenge. TikTok asked its users in Italy to confirm again that they were over 13 years old. By May, over 500,000 accounts had been removed for failing the age check. In July 2021, the Dutch Data Protection Authority fined TikTok €750,000 for offering privacy statements only in English but not in Dutch.
=== Category:EC 3.4 (act on peptide bonds - Peptidase) === Category:EC 3.4.11 Alanine aminopeptidase Category:EC 3.4.15 Angiotensin converting enzyme Category:EC 3.4.21 Serine protease Chymotrypsin (EC 3.4.21.1) Trypsin (EC 3.4.21.4) Thrombin (EC 3.4.21.5) Factor X (EC 3.4.21.6) Plasmin (EC 3.4.21.7) Acrosin (EC 3.4.21.10) Factor VII (EC 3.4.21.21) Factor IX (EC 3.4.21.22) Prolyl oligopeptidase (EC 3.4.21.26) Factor XI (EC 3.4.21.27) Elastase (EC 3.4.21.37) Factor XII (EC 3.4.21.38) Proteinase K (EC 3.4.21.64) Tissue plasminogen activator (EC 3.4.21.68) Protein C (EC 3.4.21.69) Category:EC 3.4.22 Separase (EC 3.4.22.49) Category:EC 3.4.23 Pepsin (EC 3.4.23.1) Rennet (EC 3.4.23.4) Renin (EC 3.4.23.15) Trypsinogen (EC 3.4.23.18) and (20/21/23/24/26) Plasmepsin (EC 3.4.23.39) Category:EC 3.4.24 Matrix metalloproteinase (EC 3.4.24.7) Category:EC 3.4.25 Metalloendopeptidase
=== Journal articles === —— (1927). "The Theoretical Prediction of the Physical Properties of Many-Electron Atoms and Ions. Mole Refraction, Diamagnetic Susceptibility, and Extension in Space". Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences. 114 (767): 181–211. Bibcode:1927RSPSA.114..181P. doi:10.1098/rspa.1927.0035. —— (1929). "The Principles Determining the Structure of Complex Ionic Crystals". Journal of the American Chemical Society. 51 (4): 1010–1026. Bibcode:1929JAChS..51.1010P. doi:10.1021/ja01379a006. —— (1931). "The Nature of the Chemical Bond. I. Application of Results Obtained from the Quantum Mechanics and from a Theory of Paramagnetic Susceptibility to the Structure of Molecules". Journal of the American Chemical Society. 53 (4): 1367–1400. Bibcode:1931JAChS..53.1367P. doi:10.1021/ja01355a027. —— (1931). "The Nature of the Chemical Bond. II. The One-Electron Bond and the Three-Electron Bond". Journal of the American Chemical Society. 53 (9): 3225–3237. Bibcode:1931JAChS..53.3225P. doi:10.1021/ja01360a004. —— (1932). "The Nature of the Chemical Bond. III. The Transition from One Extreme Bond Type to Another". Journal of the American Chemical Society. 54 (3): 988–1003. Bibcode:1932JAChS..54..988P. doi:10.1021/ja01342a022. —— (1932). "The Nature of the Chemical Bond. IV. The Energy of Single Bonds and the Relative Electronegativity of Atoms". Journal of the American Chemical Society. 54 (9): 3570–3582. Bibcode:1932JAChS..54.3570P. doi:10.1021/ja01348a011. ——; Wheland, G. W. (1933). "The Nature of the Chemical Bond. V.
Sources: en.wikipedia.org
==== Israel ==== Dunkin' Donuts Israel (Hebrew: דאנקן דונאטס) was an Israeli franchise of the chain. Dunkin' Donuts Israel opened their first location in Israel in 1996 in Tel Aviv. Their main flagship store was located in Rabin Square, with their factory in Lod. Upon opening their first location, Dunkin' was a huge hit. When the original location opened, it broke Dunkin's own sales records by selling 3 million doughnuts in the first eight months. The chain's manager was quoted saying "Israelis do not stop eating doughnuts, They buy such quantities, quantities that we would never have believed they would buy. They buy boxes of 12, eat them here, and then buy more boxes to take home." In 2001, when Dunkin' Donuts Israel decided to close, the company had accumulated a large amount of debt. When the Second Intifada broke out, Israeli tourism slowed, and Dunkin' decided to close. Approximately $2 million was invested in Dunkin' Donuts Israel when it failed. At the peak, Dunkin' Donuts had 9 branches in Israel, short of their original goal of 15, including 3 in Jerusalem.
Flowers removed from the plant remain alive. Respiration and photosynthesis continue, but no longer have a storehouse of sugars to support them. Additionally, the flowers no longer receive water from the roots, yet transpiration continues. In many countries, cut flowers are a local crop because of their perishable nature. In India, much of the product has a shelf life of only a day. Among these are marigold flowers for garlands and temples, which are typically harvested before dawn, and discarded after use the same day. The postharvest life or vase life of cut flowers can be several days. The vase life of cut flowers and cut greens can be extended with thoughtful care. This care starts from the moment of harvest and continues until they are enjoyed by a flower consumer. Everyone involved must participate in the, "Floral Chain-of-Life", or the life of the cut flowers and cut greens is reduced. Flowers are harvested in the cool part of the day, generally morning, and placed into water as soon as possible to reduce water loss from transpiration. The cut stems go into clean buckets with low pH water as a hydrating solution. Next, the cut stems are refrigerated to slow respiration, photosynthesis and transpiration. Vacuum coolers and hydrocoolers are used for large numbers of flowers on commercial farms. When cold, 2–4 °C (36–39 °F), the cut stems are sized and graded for shipment. Additionally, most or all of the leaves are removed from the cut flower stems to reduce the cost of shipping and reduce disease issues.
=== Bribing providers for prescriptions === In August 2025, Texas sued Lilly for allegedly "bribing" providers to prescribe Mounjaro and Zepbound. Lilly allegedly offered illegal incentives to medical providers in Texas, including "free nurses" and reimbursement support services, while the costs of the drugs were covered by Medicaid.
=== Elevated levels === Hyperprolactinaemia, or excess serum prolactin, is associated with hypoestrogenism, anovulatory infertility, oligomenorrhoea, amenorrhoea, unexpected lactation and loss of libido in women and erectile dysfunction and loss of libido in men. Causes of Elevated Prolactin Levels
== General and cited references == Gabriele Froböse, Rolf Froböse, Michael Gross (Translator): Lust and Love: Is It More than Chemistry? Royal Society of Chemistry, 2006; ISBN 0-85404-867-7. Michael Scott: Pillow Talk: A Comprehensive Guide to Erotic Hypnosis and Relyfe Programming. Blue Deck Press, 2011; ISBN 0-98341-640-0.
Sources: en.wikipedia.org
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.
Vacuum lowers the pressure below the triple point of water, allowing ice to sublimate directly into vapor. It also helps remove water vapor from the product chamber and shortens primary drying.
Many aqueous solutions and suspensions can be freeze-dried, but some formulations collapse or do not form a stable cake. The process requires careful formulation and cycle development.
Karl Fischer titration is a common reference method that quantifies water by a chemical reaction. Thermogravimetric analysis can also estimate moisture by weight loss on heating. Method choice depends on sample size and whether other volatile substances are present.