A practical reference on secondary drying: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
This page was last updated on 2025-11-26 and is reviewed periodically as new material appears.
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.
The process relies on the phase diagram of water, where the triple point marks the conditions at which ice, liquid water, and vapor coexist. By maintaining pressure below this point, typically around 0.01 to 0.1 millibar, sublimation becomes the dominant mechanism. Formulations often include excipients such as sugars or polymers that act as lyoprotectants and bulking agents. These additives help preserve the structure of the active ingredient and prevent collapse during drying. The choice of excipient and freezing rate influences the final cake morphology and stability.
Industries use lyophilization for pharmaceuticals, biological products, and food preservation. In the pharmaceutical sector, it extends the shelf life of injectable drugs, vaccines, and proteins that are unstable in aqueous solution. Food manufacturers apply freeze-drying to coffee, fruits, and ready meals to retain flavor and texture. The process is energy-intensive and requires specialized equipment, which limits its use to high-value products. Ongoing research examines how formulation and process parameters affect the quality of the final dried product.
Lyophilization, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
| Property | Value | Notes |
|---|---|---|
| Physical state | Solid, porous cake or powder | Depends on formulation and container |
| Typical storage temperature | 2–25 °C, protected from moisture | Some materials require colder conditions |
| Solubility class | Usually readily soluble after reconstitution | Not an intrinsic chemical property |
| Common analytical method | Karl Fischer titration | Used for residual moisture |
| Common synonyms | Freeze-drying; lyophilisation | Lyophilisation is a spelling variant |
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.
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.
Freezing is the first stage and sets the ice structure that later becomes the pore network. The formulation is cooled below its freezing point, often with a controlled ramp, and solutes concentrate as ice forms. Primary drying then lowers chamber pressure and supplies heat to sublime the ice. The product temperature must stay below its collapse or eutectic temperature to prevent structural loss. Secondary drying raises the temperature modestly to remove bound water and achieve a low residual moisture.
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.
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.
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.
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.
Whereas the Principal Allied Powers have also agreed that the Mandatory should be responsible for putting into effect the declaration originally made on November 2nd, 1917, by the Government of His Britannic Majesty, and adopted by the said Powers, in favor of the establishment in Palestine of a national home for the Jewish people, it being clearly understood that nothing should be done which might prejudice the civil and religious rights of existing non-Jewish communities in Palestine, or the rights and political status enjoyed by Jews in any other country.... A statement on "British Policy in Palestine," issued on 3 June 1922 by the Colonial Office, placed a restrictive construction upon the Balfour Declaration. The statement excluded "the disappearance or subordination of the Arabic population, language or customs in Palestine" or "the imposition of Jewish nationality upon the inhabitants of Palestine as a whole", and made it clear that in the eyes of the mandatory Power, the Jewish National Home was to be founded in Palestine and not that Palestine as a whole was to be converted into a Jewish National Home. The Committee noted that the construction, which restricted considerably the scope of the National Home, was made prior to the confirmation of the Mandate by the Council of the League of Nations and was formally accepted at the time by the Executive of the Zionist Organization. The Partition Resolution of the UN General Assembly died at birth when rejected by the Arabs. The UNGA has only the power to recommend.
=== Hunger === Because patients are being fed intravenously, the subject does not physically eat, resulting in intense hunger pangs (pains). The brain uses signals from the mouth (taste and smell), the stomach and gastrointestinal tract (fullness) and blood (nutrient levels) to determine conscious feelings of hunger. In cases of TPN, the taste, smell and physical fullness requirements are not met, and so the patient experiences hunger, although the body is being fully nourished. Patients who eat food despite the inability can experience a wide range of complications, such as refeeding syndrome.
=== Public utilities === Buildings in Moscow, as in other Russian cities, are warmed by district heating. Before 2004, state unitary enterprises were responsible for producing and supplying heat to clients by operating the heating stations and distribution system of Mosgorteplo, Mosteploenergo, and Teploremontnaladka; these provided service to the heating substations in the northeastern part of the city. Clients were divided among enterprises according to location. A major reform launched in 2004 consolidated companies under MIPC, which became the municipal heat supplier. Its subsidiaries were new joint-stock companies. The city's main source of heating is Mosenergo's power station, which was reformed in 2005, when about ten subsidiaries were detached. One of the newly independent companies was the District Heating Network Company (MTK) (Russian: Московская теплосетевая компания). In 2007, the Government of Moscow bought controlling stakes in this company. "Our city" is a geoinformation portal created in 2011 under Moscow's mayor, Sergei Sobyanin, to initiate constructive dialogue between Moscow residents and the city's executive authorities. This portal is being developed by the State Public Institution "New Management Technologies", together with the Moscow Department of Information Technologies. During its 10 years of operation, more than 1.7 million users have registered for the portal; it has become effective for monitoring urban infrastructure.
==== 1.C Pore-forming toxins (proteins and peptides) ==== 1.C.3 α-Hemolysin (αHL) family 1.C.4 Aerolysin family 1.C.5 ε-toxin family 1.C.11 RTX-toxin superfamily 1.C.12 Membrane attack complex/perforin superfamily 1.C.13 Leukocidin family 1.C.14 Cytohemolysin (CHL) family 1.C.39 Thiol-activated cholesterol-dependent cytolysin family 1.C.43 Lysenin family 1.C.56 Pseudomonas syringae HrpZ cation channel family 1.C.57 Clostridial cytotoxin family 1.C.58 The Microcin E492/C24 (Microcin E492) Family 1.C.74 Snake cytotoxin (SCT) family 1.C.97 Pleurotolysin pore-forming family
Sources: en.wikipedia.org
=== Darlene Conner-Olinsky === Darlene Conner-Olinsky is played by Sara Gilbert. She is Dan and Roseanne's second child and younger daughter, born in 1977. Darlene, who has inherited her mother's acerbic sense of humor, is artistic, tomboyish, and socially awkward. In the early seasons, Darlene mostly focuses on sports and, though highly intelligent, underperforms academically. She often mocks her older sister Becky for being a model student, her feminine pursuits, and for chasing boys. As a teenager, Darlene grows increasingly moody and withdrawn, her malaise gradually leading to a brief bout of depression. She is a strong animal rights activist and becomes a vegetarian, which closely reflects Gilbert's real-life views. In middle school, Darlene is generally uninterested in boys though she has a few dates. As a high school freshman, she begins dating David Healy (called Kevin Healy in his first appearance, though the name was changed). David (Johnny Galecki) is the younger brother of Becky's punk boyfriend (later husband) Mark. Darlene is sarcastic and domineering like her mother, often causing the two to clash. Her strong personality dominates the meek David, who usually defers to her. Darlene is a talented aspiring writer and David is a budding graphic artist, leading them to collaborate on a graphic novel. Darlene's goal is to become a professional writer and is talented enough to be awarded early admission and a scholarship to an arts college in Chicago. After David's application to the same school is declined, he wants Darlene to remain in Lanford.
== Tissue distribution == CART is an anorectic peptide and is widely expressed in both the central and peripheral nervous systems, particularly concentrated in the hypothalamus. CART is also expressed outside of the nervous system in pituitary endocrine cells, adrenomedullary cells, islet somatostatin cells, and in rat antral gastrin cells. Other structures and pathways associated with CART expression include the mesolimbic pathway (linking the ventral tegmental area to the nucleus accumbens) and amygdala. CART is also found in a subset of retinal ganglion cells (RGCs), the primary afferent neurons in the retina. Specifically, it labels ON/OFF Direction Selective Ganglion Cells (ooDSGCs), a subpopulation of RGCs that stratify in both the ON and OFF sublamina of the Inner Plexiform Layer (IPL) of the retina. It is also found in a subset of amacrine cells in the Inner Nuclear Layer. No role as of yet has been proposed for the location of this protein in these cell types.
== History == Effective pharmaceutical female sex-hormonal medications, including androgens, estrogens, and progestogens, first became available in the 1920s and 1930s, and might have been prescribed for transitions as early as the late 30s or 40s. The earliest report of hormone therapy in transgender women was published by Danish endocrinologist Christian Hamburger in 1953. One of his patients was Christine Jorgensen, who he had treated starting in 1950. Additional reports of hormone therapy in transgender women were published by Hamburger, the German-American endocrinologist Harry Benjamin, and other researchers in the mid-to-late 1960s. However, Benjamin had several hundred transgender patients under his care by the late 1950s, and had treated transgender women with hormone therapy as early as the late 1940s or early 1950s. In any case, Hamburger is said to be the first to treat transgender women with hormone therapy. One of the first transgender health clinics was opened in the mid-1960s at the Johns Hopkins School of Medicine. By 1981, there were almost 40 such centers. A review of the hormonal regimens of 20 of the centers was published that year. The first International Symposium on Gender Identity, chaired by Christopher John Dewhurst, was held in London in 1969, and the first medical textbook on transness, titled Transsexualism and Sex Reassignment and edited by Richard Green and John Money, was published by Johns Hopkins University Press in 1969. This textbook included a chapter on hormone therapy written by Christian Hamburger and Harry Benjamin.
==== Montessori ==== Prince George's County Public Schools has implemented two facilities dedicated to the Montessori instructional program — the Robert Goddard Montessori School and the John Hanson Montessori School. As dedicated facilities, these schools do not have a neighborhood attendance area. Entry into the program is through the random lottery application process only. The Montessori Primary Program for children ages 3 to 6 years old is based on the Montessori educational philosophy. Taught by Montessori accredited teachers, young children are guided in developing an inner discipline, strengthening their coordination, and extending their concentration span. These accomplishments result with their readily learning to read, write and grasp mathematics. The program consists of a half-day morning for preschoolers (ages 3 ). Children older than four must be enrolled in a certified Montessori program to be accepted into the program. The Montessori Lower Elementary Program is designed for students ages 6 to 9 years old with prior Montessori experience. Rapid growth and learning is observed in classrooms filled with appropriate educational materials. The Montessori Upper Elementary Program continues for the next age grouping of students ages 9–12 with prior Montessori experience. Taught by Montessori accredited teachers, these elementary program students study an integrated curriculum that includes: mathematics, geometry, language, cultural studies, astronomy, biology, chemistry, geography, history, geology, philosophy, art, music and physical education.
=== Slipping === The method of slipping is one which exploits the thermodynamic stability of the rotaxane. If the end groups of the dumbbell are an appropriate size it will be able to reversibly thread through the macrocycle at higher temperatures. By cooling the dynamic complex, it becomes kinetically trapped as a rotaxane at the lower temperature.
Sources: en.wikipedia.org
=== Medications === Oral contraceptives containing ethinylestradiol can increase SHBG levels 2- to 4-fold and decrease free testosterone concentrations by 40 to 80% in women. They can be used to treat symptoms of hyperandrogenism like acne and hirsutism. Some oral contraceptives, namely those containing high doses of ethinylestradiol (which have been discontinued and are no longer marketed), can increase SHBG levels as much as 5- to 10-fold. Some medications, such as certain anabolic steroids like mesterolone and danazol and certain progestins like levonorgestrel and norethisterone, have high affinity for SHBG and can bind to it and displace endogenous steroids from it, thereby increasing free concentrations of these endogenous steroids. It has been estimated that therapeutic levels of danazol, methyltestosterone, fluoxymesterone, levonorgestrel, and norethisterone would respectively occupy or displace from testosterone 83–97%, 48–69%, 42–64%, 16–47%, and 4–39% of SHBG binding sites, while others with low affinity for SHBG such as ethinylestradiol, cyproterone acetate, and medroxyprogesterone acetate would occupy or displace from testosterone 1% or fewer SHBG binding sites. Selective androgen receptor modulators (SARMs) also reduce SHBG.
In 1963, Carl F. Essig of the Addiction Research Center of the National Institute of Mental Health stated that meprobamate, glutethimide, ethinamate, ethchlorvynol, methyprylon and chlordiazepoxide were drugs whose usefulness “can hardly be questioned.” However, Essig labeled these “newer products” as “drugs of addiction,” like barbiturates, whose habit-forming qualities were more widely known. He mentioned a 90-day study of chlordiazepoxide, which concluded that the automobile accident rate among 68 users was 10 times higher than normal. Participants' daily dosage ranged from 5 to 100 milligrams. Chlordiazepoxide is a drug of potential misuse and is frequently detected in urine samples of drug users who have not been prescribed the drug.
=== Patent expiry === Patent protection for insulin glargine expired in the European Union and the United States in 2014. Insulin glargine from competitor Eli Lilly became available in most countries during 2015, under the brand names Basaglar (as a follow-on in the US) and Abasaglar (as a biosimilar in the EU).
==== Issue of citizenship ==== The report further stated that Russian citizenship, given to the vast part of Abkhaz and Ossetians can not be considered "legally binding under international law" and "the purportedly naturalised persons from South Ossetia and Abkhazia are not Russian nationals in terms of international law." The commission concluded that Abkhaz and South Ossetians legally were citizens of Georgia since 1993, and had not lost their Georgian citizenship at the time of the conflict. The commission also concluded: "The large-scale naturalisations of residents of South Ossetia and Abkhazia with no other factual connection to Russia must be equated to so-called collective (ex lege) naturalisations of foreign residents", which was prohibited. The commission concluded that the creation of Russian citizens in Georgia massively "may be a basis (or rather a pretext) for military intervention", and would amount as a violation of Georgia's sovereignty. The commission concluded that some parts of the Russian Law on Citizenship violated a territorial sovereignty of Georgia. The commission made conclusions that Russian "passportisation" was a meddling in Georgian affairs and demonstrated that Russia was the bad neighbour. The commission stated that humanitarian obstacles caused by Russia to the residents of Abkhazia and South Ossetia "do not justify the large-scale naturalisation of Georgian citizens." The commission stated that "Russia is not allowed under international law to issue passports directly in South Ossetia and Abkhazia, and to pay pensions there".
Sources: en.wikipedia.org
Freezing only converts liquid to solid. Lyophilization adds vacuum and controlled warming so frozen solvent sublimes, leaving a dry porous solid. The two steps are related but not interchangeable.
Reduced pressure keeps the solvent below its triple point, allowing ice to become vapor without melting. Vacuum also helps remove water vapor from the product chamber. The exact pressure is chosen with the formulation and equipment.
Residual moisture is water that remains in the dried solid after secondary drying. It is often measured by Karl Fischer titration, near-infrared spectroscopy, or thermogravimetry. Acceptable levels depend on the material and its stability profile.
Conventional drying uses heat to evaporate water from a material, while lyophilization freezes the material and removes water by sublimation under vacuum. This avoids the liquid phase and reduces thermal damage to sensitive substances. The result is a porous cake that reconstitutes quickly.