This is a working overview of primary drying, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-06-13 and is reviewed periodically as new material appears.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Primary phase change | Sublimation | Ice changes directly to vapor under reduced pressure |
| Typical chamber pressure | 0.01–0.5 mbar (1–50 Pa) | Below the triple point of water; product-specific |
| Typical product temperature during primary drying | −40 °C to −10 °C | Kept below collapse temperature |
| Typical residual moisture | 0.5–3% w/w | Target range varies by formulation and use |
| Common synonyms | Freeze-drying; lyophilisation | Lyophilization is the US spelling |
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.
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.
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.
Aqueous normal-phase chromatography (ANP) is a chromatographic technique that uses a polar stationary phase with a nonpolar mobile phase that contains water. It is "normal-phase" in the sense that polar analytes are retained by a polar stationary phase, but it differs from classical normal-phase chromatography in that the mobile phase contains water.
Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis.
== Places == Mass City, Michigan, also known as Mass, an unincorporated community in the United States Maß (Lauer) (pronounced "mass"), a river of Bavaria, Germany, left tributary of the Lauer Massachusetts (abbreviated Mass or MA), a U.S. state in New England Massachusetts Bay (abbreviated Mass Bay), a bay off the U.S. state of the same name
=== Pharmacokinetics === Risperidone undergoes hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe liver and kidney disease. The active metabolite of risperidone, paliperidone, is also used as an antipsychotic.
== Early life and education == Eke was born at the University of Nigeria Teaching Hospital in Enugu State, Nigeria. He attended Federal Government College, Wukari in Taraba State, before completing his medical degree (MBChB) at the University of Calabar. He earned a Master of Public Health (MPH) from the Harvard School of Public Health, concentrating in health policy and management. He completed residency training in Obstetrics and Gynecology in Nigeria at the Nnamdi Azikiwe University Teaching Hospital, and later at Michigan State University Obstetrics and Gynecology residency training program (now University of Michigan Health - Sparrow) in the United States. He went on to complete dual fellowships in maternal-fetal medicine and clinical pharmacology at Johns Hopkins University, where he earned a doctor of philosophy (PhD) in clinical investigation through the Graduate Training Program in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health.
Sources: en.wikipedia.org
The structure of somatostatin receptor antagonists is similar to that of the agonists. Some agonists were already approved by the FDA for clinical use, such as In-DTPA-octreotide and Ga-DOTATATE. Development started after the discovery of modifications that can be done to the octreotide group, an ssrt selective subtype agonist, to cause its agonistic effects to be lost and gain antagonistic effects. Different subtype receptor antagonists were later developed. Research has been done mostly on the sstr2 receptor antagonist, as the sstr2 receptor is expressed on most tumors. Somatostatin receptor antagonists are divided by generation based on the type of the subtype receptor antagonist. The first generation consists of sst2-ANT and BASS, which are sstr2 selective; and sst3-ODAN-8, which is selective for sstr3. After initial results of their increased sensitivity to neurocrine tumors appeared, ssrt2 selective antagonists that had even higher affinity were developed. These were LM3, JR10, and JR11, which make up the second generation. JR11 was shown to be the most effective among these 3 antagonists, and compounds that entered further clinical development to act as a PET imaging agent or therapeutic agent carried this subtype antagonist. The presence of a chelator coupled to the subtype antagonist was shown to affect the biological properties., by increasing the binding stability of the radionuclide to the rest of the compound, and increasing the binding affinity to the receptor by allowing conjugation of the radionuclide to the receptor.
Venus was of great interest in the field of planetary science due to its thick and opaque atmosphere, the atmospheres of other planets being a novel area of research at the time. In 1961 the Venera Programme was initiated by the Soviet Union, with the launch of Venera 1. The programme would go on to mark many firsts in the exploration of another planet. Despite the later successes however, Venera 1 and Venera 2, intended to flyby Venus, resulted in failure due to losses of contact. NASA would then initiate the Mariner program with the launch of Mariner 1 and Mariner 2. Mariner 1 failed shortly after launch, however Mariner 2 would become the first man-made object to flyby another planet in December 1962 when the probe passed by Venus. Later in 1965/66, Venera 3, marked the first time a man-made object made contact with another planet after it impacted Venus on March 1, 1966, despite operational difficulties resulting in loss of contact with the craft. In 1967, Mariner 5 flew by Venus and conducted atmospheric analysis.
=== Hydrogen === The element hydrogen, with one electron per neutral atom, is usually placed at the top of Group 1 of the periodic table because of its electron configuration. But hydrogen is not normally considered to be an alkali metal. Metallic hydrogen, which only exists at very high pressures, is known for its electrical and magnetic properties, not its chemical properties. Under typical conditions, pure hydrogen exists as a diatomic gas consisting of two atoms per molecule (H2); however, the alkali metals form diatomic molecules (such as dilithium, Li2) only at high temperatures, when they are in the gaseous state. Hydrogen, like the alkali metals, has one valence electron and reacts easily with the halogens, but the similarities mostly end there because of the small size of a bare proton H+ compared to the alkali metal cations. Its placement above lithium is primarily due to its electron configuration. It is sometimes placed above fluorine due to their similar chemical properties, though the resemblance is likewise not absolute. The first ionisation energy of hydrogen (1312.0 kJ/mol) is much higher than that of the alkali metals. As only one additional electron is required to fill in the outermost shell of the hydrogen atom, hydrogen often behaves like a halogen, forming the negative hydride ion, and is very occasionally considered to be a halogen on that basis.
"Absinthe's second coming" Archived 2008-12-03 at the Wayback Machine – An April 2001 article in Cigar Aficionado about the first absinthe commercially produced in France since the 1915 ban. "Swiss face sobering future after legalizing absinthe" Archived 2016-12-02 at the Wayback Machine – A March 2005 Reuters article about the legalising of absinthe in Switzerland. "The Mystery of the Green Menace" – A November 2005 Wired magazine article about a New Orleans man who has researched the chemical content of absinthe and now distills it in France "The Return of the Green Faerie" – A wine and spirit journal article about the history, ritual, and artistic cult of absinthe The Wormwood Society Archived 2006-04-24 at the Wayback Machine – An independent organisation supporting changes to the US laws and regulations concerning absinthe. Provides articles, a forum and legal information. "What Is Absinthe" – Article discussing absinthe and its effect over mind and body. Absinthe in the online Culinary Heritage of Switzerland database.
Sources: en.wikipedia.org
DX-9065a was the first synthetic compound that inhibited FXa without inhibiting thrombin. That was attained by inserting a carboxyl group which seemed to be the most important moiety for a selective binding to FXa. Those early developed small molecules yet had amidine-groups or even higher-basic functions, which were thought to be necessary as mimics for an arginine residue in prothrombin, the natural substrate of factor Xa. Nevertheless, these basic functions are also related to a very poor oral bioavailability (e.g. 2–3% for DX-9065a). In 1998 Bayer Healthcare, a pharmaceutical company started searching for low-molecular-weight direct factor Xa inhibitors with higher oral bioavailability. High-throughput screening and further optimisation at first lead to several substances from the class of isoindolinones demonstrating that much less basic substances can also act as potent Xa inhibitors to an IC50 value of up to 2 nM. Although isoindolinones have a better oral bioavailability than the original compounds it was insufficient. However, the project later lead to the class of n-aryloxazolidinones that provides substances with both high potency of inhibiting factor Xa and high bioavailability. One compound of this class, Rivaroxaban (IC50 = 0.7 nM, bioavailability: 60%), was granted marketing authorization for the prevention of venous thromboembolism in Europe and Canada in September 2008.
== Basic procedure == Cells that are to be studied need to be collected. Breaking the cell membranes open exposes the DNA along with the cytoplasm within (cell lysis). Lipids from the cell membrane and the nucleus are broken down with detergents and surfactants. Breaking down proteins by adding a protease (optional). Breaking down RNA by adding an RNase (optional). The solution is treated with a concentrated salt solution (saline) to make debris such as broken proteins, lipids, and RNA clump together. Centrifugation of the solution, which separates the clumped cellular debris from the DNA. DNA purification from detergents, proteins, salts, and reagents is used during the cell lysis step. The most commonly used procedures are: Ethanol precipitation usually by ice-cold ethanol or isopropanol. Since DNA is insoluble in these alcohols, it will aggregate together, giving a pellet upon centrifugation. Precipitation of DNA is improved by increasing ionic strength, usually by adding sodium acetate. Phenol–chloroform extraction in which phenol denatures proteins in the sample. After centrifugation of the sample, denatured proteins stay in the organic phase while the aqueous phase containing nucleic acid is mixed with chloroform to remove phenol residues from the solution. Minicolumn purification relies on the fact that the nucleic acids may bind (adsorption) to the solid phase (silica or other) depending on the pH and the salt concentration of the buffer.
==== Hillary Clinton's 2008 and 2016 presidential campaigns ==== After running for Congress in 1998, Pritzker transitioned away from electoral politics, becoming a significant donor to Democratic candidates. In this role he first met former First Lady and then-U.S. Senator Hillary Clinton, hosting a fundraiser at his Chicago home for her 2006 reelection campaign. When Clinton ran for president in 2008, she named Pritzker a national co-chair of her campaign. After Clinton withdrew from the race, he supported the party's nominee, Barack Obama, helping merge the Clinton and Obama campaigns in Illinois. While Pritzker had no official role in Clinton's 2016 presidential campaign, he was one of her largest donors, giving more than $17.5 million to her super PAC and campaign combined. Pritzker and his wife were also in attendance at Clinton's watch party in the Javits Center when she conceded the 2016 election to Donald Trump.
Sources: en.wikipedia.org
Lyophilization relies on sublimation, so water moves from solid ice to vapor without becoming liquid. The material is frozen, pressure is reduced, and controlled heat is supplied. Vapor is captured on a cold condenser, leaving a dry porous solid.
The process has three main stages: freezing, primary drying, and secondary drying. Freezing sets the ice structure, primary drying removes free ice, and secondary drying removes bound water. Each stage uses specific temperature, pressure, and time settings.
No, it is a drying method rather than a sterilization method. Removing water can limit microbial growth, but it does not reliably kill microorganisms. Sterility must come from separate steps such as filtration, heat treatment, or aseptic processing.
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.