Everything below concerns secondary drying. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-07-19. Where a claim depends on a specific study, the study is described rather than over-claimed.
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 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.
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.
| 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 |
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 physics of freeze-drying couples heat transfer, mass transfer, and phase change. Heat supplied through the shelf must reach the sublimation front without melting the ice or degrading the product. Water vapor then travels through the already dried layer and leaves the chamber, where low pressure and cold traps keep it from returning. The dried layer acts as a resistance to vapor flow, so drying rate changes as the front recedes. Open questions remain about how pore structure and formulation heterogeneity affect drying uniformity at larger scales.
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.
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.
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.
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.
Active esters are prominent in biochemistry. Glutamine synthetase is an enzyme that forms an active ester from the terminal carboxylate of glutamic acid. This activation, imparted by phosphorylation, facilitates the conversion of the carboxylate to an amide called glutamine.
== Overdose == Hydrocodone: Respiratory depression, extreme somnolence progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur. Paracetamol: Liver and kidney failure, low blood sugar, and coma may occur.
== Formation == Initial funding for the formation of Onyx came from biotechnology firm Chiron Corporation (granted a 43% stake in the new company) and venture capital investors: Avalon Ventures, Institutional Venture Partners (IVP), J. H. Whitney & Company and Kleiner Perkins. McCormick had been working on cancer treatments at Chiron before he was selected as vice president of research at the newly formed company, leading the company's research program. The acting president of the firm at its inception was Samuel D. Colella, a partner at early investor, IVP.
=== Industrial wastewater treatment === Manufacturers of antimicrobials need to improve the treatment of their wastewater (by using industrial wastewater treatment processes) to reduce the release of residues into the environment.
Annals of Clinical Biochemistry is a bimonthly peer-reviewed scientific journal covering all aspects of clinical biochemistry. The editor-in-chief is Michael J Murphy (University of Dundee). It was established 1960 and is published by SAGE Publications on behalf of The Association for Clinical Biochemistry and Laboratory Medicine.
Sources: en.wikipedia.org
Low-certainty evidence indicates that it mitigates worsening of peripheral neuropathy and disability from disease progression. Inotersen blocks gene expression of both wild-type and mutant TTR, reducing amyloid precursor. Moderate-certainty evidence suggests that it mitigates worsening of peripheral neuropathy. Long-term efficacy and safety of inotersen use in people with mutant TTR-related amyloidosis is still be evaluated in a phase-III clinical trial as of 2021. Both diflunisal and inotersen may also mitigate declines in quality-of-life, though the evidence for this effect is unclear. For people with cardiac ATTR the effect of inotersen use is inconclusive and requires further investigation. In 2018, inotersen was approved by the European Medicines Agency to treat polyneuropathy in adults with hereditary transthyretin amyloidosis. It has since been approved for use in Canada, the European Union and in the USA. Patisiran functions similarly to inotersen. Moderate-certainty evidence suggests that patisiran mitigates worsening of peripheral neuropathy and disability from disease progression. Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate of adverse events versus placebo. There is no evidence of an effect on mortality rate. A review of early data from use of patisiran in people with variant cardiac ATTR suggests that it may reduce mortality and hospitalization, however this is still being investigated and requires further investigation.
== External links == Anatomy photo: TermsCells&Tissues/connective/dense/dense1 - Comparative Organology at University of California, Davis - "Connective tissue, dense (LM, Low)" Histology at cytochemistry.net Overview at downstate.edu Archived 2016-03-03 at the Wayback Machine
Animals are multicellular, eukaryotic organisms belonging to the biological kingdom Animalia (). Animals consume organic material, breathe oxygen, have muscle cells, can reproduce sexually, and grow from a hollow sphere of cells, the blastula, during embryonic development. With few exceptions, animals are able to move. Animals form a clade, meaning that they arose from a single common ancestor. Over 1.5 million living animal species have been described, of which around 1.05 million are insects, over 85,000 are molluscs, and around 65,000 are vertebrates. It has been estimated there are as many as 7.77 million animal species on Earth. Animal body lengths range from 8.5 μm (0.00033 in) to 33.6 m (110 ft). They have complex ecologies and interactions with each other and their environments, forming intricate food webs. The scientific study of animals is known as zoology, and the study of animal behaviour is known as ethology. The animal kingdom is divided into five major clades, namely Porifera, Ctenophora, Placozoa, Cnidaria and Bilateria. Most living animal species belong to the clade Bilateria, a highly proliferative clade whose members have a bilaterally symmetric and significantly cephalised body plan, and the vast majority of bilaterians belong to two large clades: the protostomes, which include organisms such as arthropods, molluscs, flatworms, annelids and nematodes; and the deuterostomes, which include echinoderms, hemichordates and chordates, the last of which contains the vertebrates.
=== Diagnosing hEDS === Because no single gene has been identified as the sole cause of the most common type of EDS, the hypermobile type, obtaining a diagnosis is often difficult. The 2017 diagnostic criteria are as follows:
Sources: en.wikipedia.org
== Alternative names == Type V collagen has a few alternative names alpha 1 These include: type V collagen preproprotein, CO5A1_HUMAN, and collagen type V alpha. Type V collagen can also be abbreviated to COLV or collagen V.
== References == Fabbrocini G, De Vita V, Pastore F, et al. (April 2012). "Collagen induction therapy for the treatment of upper lip wrinkles". J Dermatolog Treat. 23 (2): 144–52. doi:10.3109/09546634.2010.544709. PMID 21810012. S2CID 34680894. Doddaballapur S (July 2009). "Microneedling with dermaroller". J Cutan Aesthet Surg. 2 (2): 110–1. doi:10.4103/0974-2077.58529. PMC 2918341. PMID 20808602. Asif, M., Kanodia, S. and Singh, K. (2016), Combined autologous platelet‐rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: a concurrent split‐face study. J Cosmet Dermatol, 15: 434-443. doi:10.1111/jocd.12207
Thrombotic thrombocytopenic purpura - uncommon and potentially fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ ischemia connected to diffuse microvascular platelet rich-thrombi, and microangiopathic hemolytic anemia. Relapsing polychondritis - uncommon multisystem autoimmune disease with an unclear etiology that is marked by progressive cartilaginous tissue loss and recurring episodes of inflammation. Mixed connective tissue disease - systemic autoimmune disease that shares characteristics with two or more other systemic autoimmune diseases, such as rheumatoid arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. It is an example of overlap syndrome. Undifferentiated connective tissue disease - unclassifiable systemic autoimmune disorders that do not meet any of the current classification requirements for connective tissue diseases, yet have clinical and serological signs similar to connective tissue diseases. Psoriatic arthritis - inflammatory musculoskeletal condition linked to psoriasis. Cryoglobulinemia - condition sometimes associated with systemic lupus erythematosus or rheumatoid arthritis in which there are abnormal proteins in the blood. IgG4-related disease - chronic inflammatory condition in which there is deposition of connective tissue (fibrosis) in different organs. Potentially life-threatening. Periaortitis - a group of rare vascular inflammatory diseases in which fibrous inflammatory tissue develops around the aorta or other structures such as the ureters.
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.
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.