The short version of Sublimation fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-07-30 and is reviewed periodically as new material appears.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
Residual moisture is a key quality attribute for lyophilized products. Water that remains after secondary drying can affect chemical stability, cake structure, and shelf life. Karl Fischer titration is a common method for measuring water content in the dried solid. The target range varies by product, but many biologics are dried to between 0.5% and 3% water by weight. Acceptable limits are set during development and confirmed by stability studies.
Stability studies examine how temperature, humidity, and time influence a lyophilized product. Accelerated conditions provide early information about degradation pathways, while long-term studies support shelf-life claims. The glass transition temperature of the dried formulation can indicate its physical stability, and storage above this temperature may increase molecular mobility and lead to collapse or aggregation. Container closure integrity also matters because moisture or oxygen ingress can degrade the product, so vial stoppers and seals are part of the quality system.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilisation is the British spelling; the process is not simple evaporation. |
| Primary drying pressure | 0.05–0.3 mbar | Pressure must remain below the vapor pressure of ice at the product temperature. |
| Sublimation temperature | Below 0 °C | Ice changes directly to vapor while the product remains frozen. |
| Typical shelf temperature | −40 to −10 °C | Exact setting depends on formulation critical temperature and equipment. |
| Cycle duration | 12–72 hours | Time varies with fill volume, formulation, and dryer performance. |
Lyophilization, also called freeze-drying, removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts free water into ice and may also produce a glassy phase. Primary drying then lowers chamber pressure so ice sublimes directly to vapor without passing through a liquid stage. Secondary drying raises the temperature modestly to remove bound water. The result is a porous, dry solid that usually reconstitutes quickly. Each stage influences pore structure, residual moisture, and stability.
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
Quality control for lyophilized materials includes visual inspection, residual moisture measurement, and reconstitution testing. Cake appearance can reveal process problems such as collapse, shrinkage, or meltback, although appearance alone does not prove potency. Residual moisture is commonly measured by Karl Fischer titration or by loss on drying. Reconstitution time is checked because a slow or incomplete dissolve can indicate a change in pore structure. Stability studies track these attributes over time under defined temperature and humidity conditions.
Analytical methods for lyophilized solids must account for the low moisture content and the fragile cake. Karl Fischer titration is widely used for water content, while near-infrared spectroscopy can measure moisture non-destructively in sealed containers. X-ray diffraction and modulated differential scanning calorimetry help identify crystalline or amorphous phases. Residual solvent analysis may be needed if organic solvents were used during formulation. The combination of these methods supports batch release and long-term stability assessment.
== Doubly substituted isotopologues == Measurement of the abundance of clumped isotopes (doubly substituted isotopologues) of gases has been used in the field of stable isotope geochemistry to trace equilibrium and kinetic processes in the environment inaccessible by analysis of singly substituted isotopologues alone. Currently measured doubly substituted isotopologues include:
Tetra Pak also works with Chinese schools to regulate storage, distribution and recycling of school milk. They certified 53 schools as 'Promotion Model Schools' in 2017 and aimed to certify 50 more schools in 2018. During the COVID-19 pandemic, Tetra Pak helped maintain the delivery of school feeding programmes via online orders and non-contact delivery methods. The Tetra Laval Group donates 10 million Euro to various voluntary organisations supporting health care systems. Following the 2022 Russian invasion of Ukraine, Tetra Pak condemned the invasion and Tetra Laval donated 10 million Euro towards organisations including UNICEF, Save The Children, The Red Cross and Doctors Without Borders.
=== Cellulose nanofiber plate === A bottom up approach can be used to create a high-performance bulk material with low density, high strength and toughness, and great thermal dimensional stability: cellulose nanofiber plate (CNFP). Cellulose nanofiber hydrogel is created by biosynthesis. The hydrogels can then be treated with a polymer solution or by surface modification and then are hot-pressed at 80 °C. The result is bulk material with excellent machinability. "The ultrafine nanofiber network structure in CNFP results in more extensive hydrogen bonding, the high in-plane orientation, and "three way branching points" of the microfibril networks". This structure gives CNFP its high strength by distributing stress and adding barriers to crack formation and propagation. The weak link in this structure is bond between the pressed layers which can lead to delamination. To reduce delamination, the hydrogel can be treated with silicic acid, which creates strong covalent cross-links between layers during hot pressing.
Sources: en.wikipedia.org
These early experiments with animal blood provoked a heated controversy in Britain and France. Finally, in 1668, the Royal Society and the French government both banned the procedure. The Vatican condemned these experiments in 1670. Blood transfusions fell into obscurity for the next 150 years.
In 1973, the borough increased in size when the West Rouge area, formerly within the Township of Pickering, was transferred to it with the creation of the Regional Municipality of Durham. The borough's status was changed to city in 1983. The number of aldermen was increased to 14 and the term of office extended to three years from two.
== Une ville célèbre, l’Angora ou l’antique Ancyre (A Famous city, the Angora or the Antik Ancyra) == In 1923, at the same time as publishing L’Art islamique, Raymond published a volume on the treasures of Turkey, Une ville célèbre, l’Angora ou l’antique Ancyre (A Famous City, Angora or Antique Ancyra) once again with Schulz. It also discusses the history of Ankara. This book is dedicated to the memory of Pierre Loti. The book was reviewed in a 1926 edition of Revue des études byzantines by L. Barral, who called it "abundantly but unevenly illustrated". He praised Raymond's plan of the town of Yeni-Chéir, and twelve plates of the Temple of Augustus and Rome, particularly two where Raymond had "attempted an interesting reconstruction of the same temple transformed into a church".
Sources: en.wikipedia.org
A growing number of cases seek to enforce liability on gas, oil and coal polluters. In Friends of the Earth v Royal Dutch Shell plc, the Hague District Court held that Shell was bound by the tort provisions of the Dutch Civil Code, Book 6, section 162(2), interpreted in light of the Paris Agreement 2015 article 2(1) and ECHR articles 2 and 8 (rights to life and home), to immediately start cutting all of its emissions by 45% by 2030, whether generated directly by its corporate group (scope 1), indirectly from its purchases (scope 2), or indirectly from its value chain or the purchase and use of its products (scope 3). It emphasised the 'serious and irreversible consequences of dangerous climate change in the Netherlands... pose a threat to the human rights of Dutch residents'. After this loss, Shell dropped "Royal Dutch" from its name, and moved its headquarters to London. In Lliuya v RWE AG Mr Lliuya, who lives in Huaraz, Peru has claimed that RWE AG should pay 0.47% of the costs of flood defences against a melting mountain glacier that increases the size of Lake Palcacocha, because RWE is responsible for 0.47% of historic global greenhouse gas emissions. The Higher Regional Court of Essen gave leave to appeal on whether there is causation of damage, and in 2022 visited the lake. There has also been heightened responsibility on member state governments.
== Mechanisms == The effective overall energy unit for the available body energy is referred to as the daily glycogen generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the mitochondria in all of the cells of the human body; however, the relation between the energy generated by the mitochondria and the glycogen capacity is very loose and is mediated by many biochemical pathways. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable.
=== Dimerization === Dimerization of CK1δ has also been described as a regulatory mechanism through the interaction interface contained by the DD of CK1δ. Following dimerization, Arg-13 inserts into the adenine binding pocket and prevents binding of ATP and perhaps also of large substrates. Although CK1δ in solution is always purified as monomers, biological relevance of dimerization could be demonstrated by showing that the binding of dominant-negative mutant CK1δ to wild type CK1δ resulted in the total reduction of CK1δ-specific kinase activity.
=== Malaysia === According to the Malaysian Food Act 1983 and Regulations (as of 5 January 2010), ractopamine is allowed in pig muscle and fat (MRL of 10 ppb), pig liver (MRL of 40 ppb), and pig kidney (MRL of 90 ppb). Ractopamine is allowed as its half-life is lower, leading to reduced residues in the food, and the dose required to affect humans is much higher than other beta agonists. On 30 December 2008, the Malaysian Veterinary Services Department quarantined 10 of the 656 pig farms in Malaysia, as the livestock were found to contain the banned chemical.
Sources: en.wikipedia.org
The main change is sublimation, in which ice becomes water vapor without melting into liquid water. This occurs when the chamber pressure is held below the vapor pressure of ice while mild heat is supplied. The result is a dry, porous solid that retains much of its original shape.
Freezing determines ice crystal size, solute distribution, and the pore network left after drying. A slow or fast freezing rate can produce different cake structures and affect reconstitution. It also sets whether the formulation follows an amorphous or crystalline drying path.
It removes most free water during primary drying and part of the bound water during secondary drying. A small residual moisture content often remains and is specified for each product. Complete removal is generally neither practical nor desirable for stability.
Residual moisture can influence chemical degradation, cake collapse, and long-term stability. Low moisture levels usually improve stability, but each product has an optimal range.