secondary drying raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
This page was last updated on 2026-04-19 and is reviewed periodically as new material appears.
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.
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.
After lyophilization, a product's quality depends on residual moisture, cake appearance, and reconstitution time. Residual moisture is often measured by Karl Fischer titration or thermogravimetric analysis. A low moisture content can slow chemical degradation, but overly dry cakes may be brittle or slow to dissolve. Stability studies track these attributes over months under defined temperature and humidity conditions. Batch records link these measurements to specific process runs and help identify trends before a product fails specification.
| Property | Value | Notes |
|---|---|---|
| Process name | Lyophilization or freeze-drying | Both terms appear in technical standards and literature. |
| Phase transition | Sublimation | Solid ice becomes vapor without a liquid step. |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product temperature and equipment. |
| Typical product temperature | -40 °C to -10 °C | Measured during primary drying; formulation sets limits. |
| Water content after drying | 0.5-3% w/w | Target varies by material and stability needs. |
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.
Quality control for freeze-dried forms includes visual inspection, water content measurement, and reconstitution time. A satisfactory cake is typically uniform, porous, and intact, although minor shrinkage or cracking may be acceptable if specifications allow. Karl Fischer titration, thermal gravimetric analysis, and near-infrared spectroscopy are used to measure water content. Reconstitution is assessed by adding a specified diluent and recording the time and ease of dissolution. Microbiological and particulate tests are added when the product is sterile or intended for injection.
Stability of a lyophilized solid depends on water content, temperature, and the physical state of the formulation. Amorphous products may slowly absorb moisture and drop below their glass transition temperature, causing collapse or crystallization. Some proteins and peptides can aggregate even in a dry state, especially when exposed to heat or moisture. Accelerated stability studies at elevated temperature and humidity help estimate shelf life, but real-time data remain the basis for expiration dating.
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.
Ernst on developing the first two-dimensional NMR experiments, and established the nuclear Overhauser effect as a convenient way of measuring distances within proteins. This research later led to the complete assignment of resonances for among others the bovine pancreatic trypsin inhibitor and glucagon. In October 2010, Wüthrich participated in the USA Science and Engineering Festival's Lunch with a Laureate program where middle and high school students will get to engage in an informal conversation with a Nobel Prize–winning scientist over a brown-bag lunch. Wüthrich is also a member on the USA Science and Engineering Festival's Advisory Board and a supporter of the Campaign for the Establishment of a United Nations Parliamentary Assembly, an organisation which campaigns for democratic reform in the United Nations. Wüthrich is a member of the Executive Advisory Board of the World.Minds Foundation, where he contributes to international dialogue on science, research, and innovation policy.
=== Pharmacokinetics and pharmacodynamics === Oral isotretinoin is best absorbed when taken with a high-fat meal because it has a high level of lipophilicity. The efficacy of isotretinoin doubles when taken after a high-fat meal compared to when taken without food. Due to isotretinoin's molecular relationship to vitamin A, it should not be taken with vitamin A supplements due to the danger of toxicity through cumulative overdosing. Accutane also negatively interacts with tetracycline, another class of acne drug, and with micro-dosed ('mini-pill') progesterone preparations, norethisterone/ethinylestradiol ('OrthoNovum 7/7/7'), St. John's Wort, phenytoin, and systemic corticosteroids. Isotretinoin is primarily (99.9%) bound to plasma proteins, mostly albumin. Three metabolites of isotretinoin are detectable in human plasma after oral administration: 4-oxo-isotretinoin, retinoid acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin). Isotretinoin also oxidizes, irreversibly, to 4-oxo-isotretinoin—which forms its geometric isomer 4-oxo-tretinoin. After an orally administered 80 mg dose of liquid suspension 14C-isotretinoin, 14C-activity in blood declines with a half-life of 90 hours. The metabolites of isotretinoin and its conjugates are then excreted in the subject's urine and faeces in relatively equal amounts. After a single, 80 mg oral dose of Isotretinoin to 74 healthy adult subjects under fed conditions, the mean ±SD elimination half-life (t1/2) of isotretinoin and 4-oxo-isotretinoin were 21.0 ± 8.2 hours and 24.0 ± 5.3 hours, respectively.
==== Benign soft tissue neoplasms ==== Peripheral nerve sheath tumours: These most commonly are traumatic neuromas, a reactive response to trauma, neurilemmoma and neurofibroma which are large growing painless tumours usually found on the tongue. Neurofibroma may occur as a benign solitary lesion but can present as multiple lesions associated with (Von Reckllinghausen's Disease) neurofibromatosis. They can be preceded by café au lait pigmentation spots on the skin, and as they grow can become very disfiguring. Malignant change can occur in neurofibromatosis but very rarely in single lesion presentation. Mucosal neuromas can be associated with other conditions such as multiple endocrine neoplasia (MEN) syndrome and may precede thyroid cancer. Lipoma and fibrolipoma: These are tumours of adipose tissue, or fat, giving them a yellow appearance which varies according to fat content. They are usually soft, mobile, slow growing painless and occur mostly in middle age or the elderly. Granular cell tumour: These are also tumours arising from neural cells, though it was incorrectly thought to arise from muscle cells and therefore previously called granular cell myoblastoma. It also is slow growing large painless and occurs mostly in the tongue. Congenital epulis: These are also known as congenital granular cell tumours (but not related to granular cell tumours), and occur mostly on the upper gum, the maxillary alveolar ridge, of newborns, predominantly females. Rarely, they occur elsewhere, usually the tongue. They are usually self-resolving.
Fonterra's whey proteins have been key ingredients in foods and nutritional products sold around the world, including sports, medical, and beverage applications, and Fonterra continues to be a leading global supplier of whey protein.
Sources: en.wikipedia.org
Much of the work behind production of monoclonal antibodies is rooted in the production of hybridomas, which involves identifying antigen-specific plasma/plasmablast cells that produce antibodies specific to an antigen of interest and fusing these cells with myeloma cells. Rabbit B-cells can be used to form a rabbit hybridoma. Polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low, so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase (HGPRT), an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is also disrupted. Exposing cells to aminopterin (a folic acid analogue which inhibits dihydrofolate reductase) makes them unable to use the de novo pathway and become fully auxotrophic for nucleic acids, thus requiring supplementation to survive. The selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin and thymidine. This medium is selective for fused (hybridoma) cells. Unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells referred to as hybridomas, are able to grow indefinitely in the medium because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal (similar to a cancer cell).
Filament end-tracking protein (Formins, VASP and N-WASP) Filament-nucleator known as the Arp2/3 complex (Actin-related protein-2/3) Filament cross-linkers (e.g., α-actinin, fascin, and fimbrin) Actin monomer-binding proteins profilin and thymosin β4 Filament barbed-end cappers such as Capping Protein and CapG, etc. Filament-severing proteins like gelsolin. Actin depolymerizing proteins such as ADF/cofilin. The actin filament network in non-muscle cells is highly dynamic. The actin filament network is arranged with the barbed-end of each filament attached to the cell's peripheral membrane by means of clamped-filament elongation motors, the above-mentioned "actoclampins", formed from a filament barbed-end and a clamping protein (formins, VASP, Mena, WASP, and N-WASP). The primary substrate for these elongation motors is profilin-actin-ATP complex which is directly transferred to elongating filament ends. The pointed-end of each filament is oriented toward the cell's interior. In the case of lamellipodial growth, the Arp2/3 complex generates a branched network, and in filopodia a parallel array of filaments is formed.
The Beltrán-Leyva Cartel was founded by the four Beltrán Leyva brothers: Marcos Arturo, Carlos, Alfredo and Héctor. In 2004 and 2005, cartel leader Arturo Beltrán Leyva led groups of enforcers to compete for trafficking routes in northeastern Mexico against the Sinaloa Cartel. The Beltrán-Leyva Cartel infiltrated Mexico's political, judicial, and police institutions, including the Interpol in Mexico, to feed classified information about anti-drug operations against its rivals. Following the 2009 killing of Arturo Beltrán Leyva, the cartel entered into an internal power struggle between Arturo's brother, Héctor Beltrán Leyva, and his top enforcer Edgar Valdez Villarreal. Meanwhile, the cartel continued to dissolve with factions such as the South Pacific Cartel, La Mano Con Ojos, Independent Cartel of Acapulco, and La Barredora forming and the latter two cartels starting yet another intra-Beltrán Leyva Cartel conflict. The Mexican Federal Police considers the cartel to have been disbanded, and their last leader, Héctor Beltrán Leyva, was captured in October 2014.
Also in 2012, the group of Juho Rousu at University of Helsinki, Finland, introduced a machine learning method to predict molecular properties from tandem MS data. This concept was brought together with the fragmentation tree concept in 2015 resulting in CSI:FingerID, being introduced in SIRIUS 3. The fragmentation tree is used to predict a molecular fingerprint of the unknown molecule using machine learning, which in turn is used to search a molecular structure database such as PubChem. Molecular structure databases are orders of magnitude larger than reference spectra libraries (PubChem containing ~111 million compounds in 2021 compared to NIST Tandem Mass Spectral Library containing ~50.000 compounds in 2023). This kind of structure identification refers to the identity and connectivity (with bond multiplicities) of the atoms, but not stereochemistry information. Elucidation of stereochemistry is currently beyond the power of automated search engines. SIRIUS 3 also introduced the graphical user interface (GUI). In 2020, in cooperation with the group of Pieter C Dorrestein at UC San Diego, USA, molecular formula identification was improved based on derivative networks from complete biological datasets to rank molecular formula candidates. This method is called ZODIAC and has been integrated into SIRIUS 4. Also in 2020, in cooperation with Rousu's and Dorrestein's groups, CANOPUS for systematic compound class annotation was introduced to SIRIUS 4.
==== Portugal ==== Founded in 1970, the SEDES is one of the oldest Portuguese civic associations and think tanks. Contraditório think tank was founded in 2008. Contraditório is a non-profit, independent and non-partisan think tank.
Sources: en.wikipedia.org
In advanced cases, bulging of the cornea can result in a localized rupture of Descemet's membrane, an inner layer of the cornea. Aqueous humor from the eye's anterior chamber seeps into the cornea before Descemet's membrane reseals. The patient experiences pain and a sudden severe clouding of vision, with the cornea taking on a translucent milky-white appearance known as a corneal hydrops. Although disconcerting to the patient, the effect is normally temporary and after a period of six to eight weeks, the cornea usually returns to its former transparency. The recovery can be aided nonsurgically by bandaging with an osmotic saline solution. Although a hydrops usually causes increased scarring of the cornea, occasionally it will benefit a patient by creating a flatter cone, aiding the fitting of contact lenses. Corneal transplantation is not usually indicated during corneal hydrops.
Although scientifically obsolete because it does not meet the definition of a complementary color in which a neutral or black color must be mixed, it is still a model used in artistic environments, causing confusion about primary and complementary colors. It can be considered an approximation of the CMY color model. The RYB color model relates specifically to color in the form of paint and pigment application in art and design. Other common color models include the light model (RGB) and the paint, pigment and ink CMY color model, which is much more accurate in terms of color gamut and intensity compared to the traditional RYB color model, the latter emerging in conjunction with the CMYK color model in the printing industry.
=== Lymph production === Because the pores in the hepatic sinusoids are very permeable and allow ready passage of both fluid and proteins into the perisinusoidal space, the lymph draining from the liver usually has a protein concentration of about 6 g/dl, which is only slightly less than the protein concentration of plasma. Also, the high permeability of the liver sinusoid epithelium allows large quantities of lymph to form. Therefore, about half of all the lymph formed in the body under resting conditions arises in the liver.
radical Also free radical. Any atom, molecule, or ion that has at least one unpaired valence electron. With few exceptions, such unpaired electrons make radicals highly chemically reactive, and therefore organic radicals are usually short-lived.
Sources: en.wikipedia.org
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.
Lowering pressure reduces the boiling point of water and allows ice to sublimate at temperatures below freezing. Vacuum also limits convective heat transfer, so heat is usually supplied by shelves or radiation. The pressure must stay below the vapor pressure of ice at the product temperature.
The cycle typically includes freezing, primary drying, and secondary drying. Freezing solidifies water and sets the pore structure; primary drying removes bulk ice; secondary drying removes bound water. Some cycles add annealing or pre-freezing steps.
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.