If you have been reading about Secondary drying and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Updated 2025-10-23. Numbers and descriptions here follow the published literature rather than marketing material.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | freeze-drying, lyophilisation, cryodesiccation | Lyophilization is common in pharmaceutical literature. |
| Typical chamber pressure during primary drying | 0.05–0.5 mbar (5–50 Pa) | Must remain below the triple point of water. |
| Typical shelf temperature during freezing | −40 to −20 °C | Lower temperatures may be used for eutectic systems. |
| Typical residual moisture after secondary drying | 0.5–3% w/w | Product-dependent; low moisture improves stability but can cause over-drying. |
| Typical analytical method for residual moisture | Karl Fischer titration or loss on drying | Thermogravimetric methods are also used. |
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.
Lyophilization removes water by freezing a material and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intermediate liquid state. Because the material remains frozen during primary drying, the structure often stays porous. This porous matrix can rehydrate quickly when water is added back. The low pressure also allows vapor to leave the solid matrix without boiling.
The process generally proceeds in three stages: freezing, primary drying, and secondary drying. During freezing, controlled cooling converts water into ice and may also crystallize or vitrify solutes. In primary drying, the pressure is lowered below the triple point, and heat is supplied so ice sublimes directly to vapor. Secondary drying removes water that remains bound to the solid matrix, yielding a low final water content. Product temperature must stay below the collapse or glass transition temperature to maintain structure. Cycle design therefore balances shelf temperature, chamber pressure, and time.
Freeze-drying is used for materials whose activity or structure depends on low temperature and low water content. Examples include certain biologics, diagnostic reagents, starter cultures, coffee, and porous inorganic precursors. The dried product forms a cake whose porosity aids rapid wetting and dissolution. Main drawbacks are high energy use, long cycle times, and sensitivity to formulation and equipment variation. Questions remain about how freezing rates and ice morphology affect batch uniformity, especially when moving from laboratory to production scale.
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.
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 legion was probably founded by Diocletian to help defend the Danube. I Pontica: the legion was founded by Dioceltian to help defend Pontus Polemoniacus. The legion was stationed in Trapezus. Legio II II Armeniaca II Britannica: comitatensis under Magister Peditum II Flavia Constantia: comitatensis under the command of the Magister Peditum II Flavia Virtutis: comitatensis under the command of the Magister Peditum II Herculia (devoted to Hercules): levied by Diocletian, stationed in Scythia Minor II Isaura II Iulia Alpina: pseudocomitatensis under the command of the Magister Peditum, in Comes Illyricum command. It was probably founded by Crispus or Constans. Its objective was to defend Alpes Cottiae II Felix Valentis Thebaeorum: comitatensis Legio III III Diocletiana III Flavia Salutis: comitatensis unit of the Late Roman Empire under the command of the Magister Militum in the west. The Legio III Flavia Salutis was raised by either Constantius II or Diocletian and was used to guard North Africa. III Herculea: comitatensis under the command of the Comes Illyricum III Isaura III Iulia Alpina: comitatensis under the command of the Magister Peditum command in Italy Legio IV IV Italica IV Martia IV Parthica Legio V V Iovia (maybe the Jovians) V Parthica Legio VI VI Gemella VI Gallicana VI Herculia (maybe the Herculians) VI Hispana VI Parthica Legio XII XII Victrix
=== Photodetector devices === Quantum dot photodetectors (QDPs) can be fabricated either via solution-processing, or from conventional single-crystalline semiconductors. Conventional single-crystalline semiconductor QDPs are precluded from integration with flexible organic electronics due to the incompatibility of their growth conditions with the process windows required by organic semiconductors. On the other hand, solution-processed QDPs can be readily integrated with an almost infinite variety of substrates, and also postprocessed atop other integrated circuits. Such colloidal QDPs have potential applications in visible- and infrared-light cameras, machine vision, industrial inspection, spectroscopy, and fluorescent biomedical imaging.
=== Journalistic opinions and investigations === Through the years, Ana Leal's investigative journalism in TVI brought new leads to Mendonça's case, always before the police. She followed leads from the Benidorm video, information from various pedophile photos from Holland and Switzerland. According to the journalist "it only has one explanation: negligence from the many teams of the Judiciary Police (...) There wasn't a political desire (..) They got followed TVI's investigations (...) it was annoying for TVI to be ahead (...) shame to a PJ team." In two photos presented in the PJ (Judiciary Police) process for a SIC report, the inspector Luís Bordadágua said that it was possible to see resemblances with Mendonça in the archives found with pedophiles. The reconnaissance was hindered due to the boy having his eyes shut in one of the photos. A Public Ministry agent alleged that the leads were fake and the PJ said later that they did not have leads to follow such a line of investigation. In another photo that Ana Leal had access to in 2002 and gave to the judiciary power, it's possible to see a gagged boy with signs of torture that the family recognized as Mendonça. With the appearance of these leads, Ricardo Sá Fernandes questioned the "worrying social passivity of the authorities of the European Union to destroy the international pedophile ring" and the "lack of capacity for investigation, mainly at a European level".
Vasoactive intestinal polypeptide receptor 1 also known as VPAC1, is a protein, that in humans is encoded by the VIPR1 gene. VPAC1 is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes, liver, small intestine, heart, spleen, placenta, kidney, thymus and testis.
Sources: en.wikipedia.org
To treat complications, medications can be prescribed including midodrine for autonomic neuropathy, amiodarone for patients with atrial fibrillation to prevent arrhythmias, and warfarin used after a cardioembolic episode. Familial (ATTRm-CM) Treatment: In recent years there have been developments in the treatment of Familial/Transthyretin cardiac amyloidosis including methods to suppress transthyretin production, stabilize amyloid fibrils, and medications that can destroy already existing fibrils. For familial amyloidosis, ACE-inhibitors and beta-blockers can be prescribed if there is no autonomic neuropathy.
== History == Nemonapride was developed by scientists at Yamanouchi Pharmaceuticals via structural modification of the benzamide antiemetic and gastroprokinetic agent metoclopramide. It was first described in the scientific literature by 1980. The name nemonapride was first used by 1989 and this name was designated as its INNTooltip International Nonproprietary Name in 1991. The drug was launched in May 1991. However, other sources state that it was launched in 1997.
Some nuclei can undergo double beta decay (2β) where the charge of the nucleus changes by two units. Double beta decay is difficult to study, as it has an extremely long half-life. In nuclei for which both β decay and 2β are possible, the rarer 2β process is effectively impossible to observe. However, in nuclei where β decay is forbidden but 2β is allowed, the process can be seen and a half-life measured. Thus, 2β is usually studied only for beta stable nuclei. Like single beta decay, double beta decay does not change A; thus, at least one of the nuclides with some given A has to be stable with regard to both single and double beta decay. "Ordinary" 2β results in the emission of two electrons and two antineutrinos. If neutrinos are Majorana particles (i.e., they are their own antiparticles), then a decay known as neutrinoless double beta decay will occur. Most neutrino physicists believe that neutrinoless 2β has never been observed.
The raised square bar and multilevel dining became the company standard. Dallas doubled the sales and tripled profits of TGI Fridays' previous best. Families began visiting the new suburban locations during the day for casual food; "it took six or seven years, but T.G.I. Fridays became a very different animal", Stillman said. Attracted by this performance, he merged into the Dallas franchise, forming TGI Fridays, Inc., and Scoggin was the CEO for the next 15 years. Scoggin is credited with the then-new 200-seat prototype and many of the TGI Fridays innovations including a large from-scratch menu, potato skins, bartender Olympics, and frozen drinks. In 1975, the company was sold to Carlson Companies, and Stillman and the original investors departed. Stillman kept the original location and, now married, founded Smith & Wollensky in 1977 with Benson. Scoggin continued as CEO on an earn-out contract and finalized his sale in 1980, signing a new contract to continue as the company's CEO. When the company was passing through the 100-store mark, it issued an initial public offering in 1983 with Goldman Sachs. Scoggin developed the first international franchise and the template for future international development. The first restaurant was opened in the UK with Whitbread PLC. By the time Scoggin departed in 1986, the company had widened its appeal: alcohol consumption was de-emphasized, and quality was emphasized over quantity. The company became privately held again in 1989. The focus was then switched from singles to families.
ERAP1 belongs to the oxytocinase subfamily of the M1-family of zinc metalloproteases. It is composed of four structural domains. Domain I (residues 1–254) consists of an eight-stranded ß-sheet and provides binding sites for the N-terminus of substrates. It fits against the catalytic domain II and engages with domain IV through an elongated loop. Domain II (residues 255–529) is the thermolysin-like catalytic domain, composed by an alpha-helix and a five stranded beta sheet. This sheet comprises the specific for exopeptidases GAMEN motif which creates one part of the substrate binding-cleft. The catalytic Zn atom is coordinated by the residues His353, His357 and Glu386, found in the zinc-binding motif (H-E-X-X-H-X18-E) on the helix 6a. Domain III (residues 530–614) is composed by two beta-sheets forming a beta sandwich and acts as a linker between domains II and IV. Finally, domain IV (615–941) consists mainly of a-helices and exhibits a bowl-shaped form. At the closed (active) state, it juxtaposes with domain II forming a large internal cavity, which holds the C-term substrate binding site (Figure 2A). It is the most variable domain among this family of aminopeptidases.
Sources: en.wikipedia.org
In the US, chlorothalonil is used predominantly on peanuts (about 34% of usage), potatoes (about 12%), and tomatoes (about 7%), although the EPA recognizes its use on many other crops. It is also used on golf courses and lawns (about 10%) and as a preservative additive in some paints (about 13%), resins, emulsions, and coatings. Chlorothalonil is commercially available in many different formulations and delivery methods. It is applied as a dust, dry or water-soluble grains, a wettable powder, a liquid spray, a fog, and a dip. It may be applied by hand, by ground sprayer, or by aircraft.
Hydrogen ions, or protons, will diffuse from a region of high proton concentration to a region of lower proton concentration, and an electrochemical concentration gradient of protons across a membrane can be harnessed to make ATP. This process is related to osmosis, the movement of water across a selective membrane, which is why it is called "chemiosmosis". ATP synthase is the enzyme that makes ATP by chemiosmosis. It allows protons to pass through the membrane and uses the free energy difference to phosphorylate adenosine diphosphate (ADP) into ATP. The ATP synthase contains two parts: F0 and F1. The breakdown of the proton gradient leads to conformational change in F1—providing enough energy in the process to convert ADP to ATP. The generation of ATP by chemiosmosis occurs in mitochondria and chloroplasts, as well as in most bacteria and archaea. For instance, in chloroplasts during photosynthesis, an electron transport chain pumps H+ ions (protons) in the stroma (fluid) through the thylakoid membrane into the thylakoid spaces. The stored energy is used to photophosphorylate ADP, making ATP, as protons move through ATP synthase.
In the therapeutic long term, the emplacement of a prosthetic breast through a periareolar incision tends to a greater rate of incidence of capsular contracture, and also risks severing the breastmilk ducts and the nerves of the NAC, which would impede breastfeeding. Transaxillary incision: The plastic surgeon makes an incision at the axilla area (armpit) that allows tunnelling medially (cutting across) under the skin of the thorax — from the armpit to the bust area of the chest — in order to emplace the breast prosthesis into the implant-pocket of the breast to be augmented. The surgeon emplaces the prosthetic breast by cutting the cross-wise tunnel either bluntly (by hand) or mechanically (with an endoscope). The surgical approach of the transaxillary incision avoids cutting and scarring the skin envelope of the breast. The technical challenge is determining the ideal position of the prosthetic-breast within the implant-pocket in order to achieve a symmetrical breast hemisphere. Transumbilical incision: To realise an endoscopic TUBA procedure (trans-umbilical breast augmentation), the surgeon makes an incision at the navel to allow tunneling superiorly (cutting upwards) under the abdominal skin — from the waist to the chest — in order to emplace the saline prosthetic breast into the implant-pocket of the breast to be augmented. The endoscopic surgical approach of the TUBA incision avoids cutting and scarring the skin envelope of the breast.
== Lawsuits == In 1998, GNC was accused of purposely running its franchisees out of business in order to "retake" the stores into corporate control. An April 30, 2003, article states that the GNC corporate company was sued by numerous franchise owners. The complaint is that the parent company was allowing their corporate owned stores to sell products for less than the franchise stores are allowed to sell them for. The suit also claimed that GNC charged high "reset fees" to franchisees when there is new signage that needs to be changed in the store or an image facelift that must be done by GNC corporate. A similar lawsuit was filed again in an article written on October 20, 2004. In February 2015, New York Attorney General Eric Schneiderman sent cease and desist letters to GNC and other major retailers due to concerning laboratory tests regarding the accuracy of the claimed contents of supplements. GNC shortly afterwards removed some stock from sales while working with the Attorney General. In September 2016, GNC, the New York Office of the Attorney General, and other supplement retailers ultimately came to an agreement and retailers are now accomplishing more robust testing of supplements to ensure accurate labeling. In October 2015, the Attorney General of Oregon filed a lawsuit against GNC alleging that the company knowingly sold products containing the ingredients picamilon and BMPEA, which are banned by the FDA.
Sources: en.wikipedia.org
Yes, the terms are generally interchangeable. Lyophilization is more common in pharmaceutical and laboratory contexts, while freeze-drying appears widely in food science and general writing. Both describe removal of solvent by sublimation under vacuum after freezing.
Reduced pressure keeps the process below the triple point of water, so ice can sublimate directly to vapor. It also lowers the temperature needed for drying, which helps preserve heat-sensitive materials. Without vacuum, melting or boiling could occur instead of controlled sublimation.
The rate depends on heat transfer to the product and mass transfer of vapor through the dried layer. A cold condenser, adequate vacuum, and suitable shelf temperature all influence speed. Formulation properties such as solid content and collapse temperature also set practical limits.
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.