sublimation comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2025-11-28. Where a claim depends on a specific study, the study is described rather than over-claimed.
Lyophilization, also called freeze-drying, is a dehydration process in which a solvent, usually water, is frozen and then removed by sublimation under reduced pressure. The method preserves heat-sensitive materials that would degrade in conventional drying. Large-scale use grew during the mid-twentieth century for blood plasma and antibiotics, and it later expanded to vaccines, enzymes, foods, and advanced materials. The process produces a dry, porous solid that usually reconstitutes rapidly. It is distinct from simple evaporation because the solvent bypasses the liquid phase during primary removal.
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.
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 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.
| Property | Value | Notes |
|---|---|---|
| Common names | Lyophilization; freeze-drying | Terms used interchangeably. |
| Phase change | Sublimation | Ice converts directly to vapor under vacuum. |
| Typical chamber pressure | 0.01–1 mbar | Below the triple point of water. |
| Primary drying product temperature | −40 to −10 °C | Kept below collapse or glass transition temperature. |
| Water content after drying | 0.5–3% w/w | Varies with formulation and cycle. |
Equipment for lyophilization includes a vacuum chamber, temperature-controlled shelves, a condenser, and a vacuum pump. A refrigeration system cools the shelves and condenser below the product's freezing point. Process monitoring often uses Pirani and capacitance manometers, thermocouples, and resistance sensors. Cycle development balances product quality with time and energy use. Some products are annealed during freezing to improve crystallization of bulking agents. Open questions remain about scaling cycles between laboratory, pilot, and production freeze-dryers.
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.
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.
=== Economics === Tavaborole began phase III clinical trials in December 2010 and was approved by the US FDA in July 2014. Originally developed by Anacor, it is now marketed in the United States by Novartis subsidiary Sandoz. Anacor was paid US$65 million and also entered into a profit sharing scheme for future sales.
== Pathophysiology == In cases of hypersomatotropism the growth hormone concentrations that circulate are chronically increased; however, the secretion of growth hormone remains the same. Growth hormone directly and indirectly affects the metabolic system; stimulation of IGF-1 synthesis is the indirect cause. Increased levels of growth hormone and IGF-1 result in proliferation of bone, cartilage, soft tissue, and increases the size of organs. These changes are responsible for the physical changes of hypersomatotropism that are characteristic to the condition. Both growth hormone and IGF-1 can impact insulin in different manners. Chronic growth hormone excess has been linked to defects in hepatic and extrahepatic insulin actions. Growth hormone increases hepatic glucose production and decreases glucose uptake in extrahepatic tissue. Studies have suggested that growth hormone excess reduces insulin sensitivity. IGF-1 increases insulin sensitivity in both hepatic and extrahepatic tissue; however, in hypersomatotropism IGF-1 levels are unable to deal with the insulin resistance caused by excessive growth hormone levels. In non-diabetic cases the insulin resistance is countered by increased insulin production from beta cells, which results in normoglycaemia (normal levels of blood sugar) being maintained. When beta cells fail to provide enough insulin production to compensate for the increased resistance diabetes mellitus develops. The cause for this failure is unknown. The vast majority of cats with hypersomatotropism also have diabetes mellitus.
Loss of perivascular collagen occurs; it is thought that this is due to the degradative enzymes released by extravasating leukocytes, such that the collagen and other connective tissue fibers surrounding blood vessels in the area dissolve. When this occurs the gums will appear bright red and either bulbous or rounded, from all the excess fluid building up in the infected area. The initial lesion appears within two to four days of gingival tissue being subjected to plaque accumulation. When not generated through clinical experimentation, the initial lesion may not appear at all, and instead, a detectable infiltrate similar to that of the early lesion, explained below, appears.
It was first synthesised in 1811 by Pierre Louis Dulong, who lost three fingers and an eye to its explosive tendencies. As a dilute gas it is less dangerous and is thus used industrially to bleach and sterilise flour. Nitrogen tribromide (NBr3), first prepared in 1975, is a deep red, temperature-sensitive, volatile solid that is explosive even at −100 °C. Nitrogen triiodide (NI3) is still more unstable and was only prepared in 1990. Its adduct with ammonia, which was known earlier, is very shock-sensitive: it can be set off by the touch of a feather, shifting air currents, or even alpha particles. For this reason, small amounts of nitrogen triiodide are sometimes synthesised as a demonstration to high school chemistry students or as an act of "chemical magic". Chlorine azide (ClN3) and bromine azide (BrN3) are extremely sensitive and explosive. Two series of nitrogen oxohalides are known: the nitrosyl halides (XNO) and the nitryl halides (XNO2). The first is very reactive gases that can be made by directly halogenating nitrous oxide. Nitrosyl fluoride (NOF) is colourless and a vigorous fluorinating agent. Nitrosyl chloride (NOCl) behaves in much the same way and has often been used as an ionising solvent. Nitrosyl bromide (NOBr) is red. The reactions of the nitryl halides are mostly similar: nitryl fluoride (FNO2) and nitryl chloride (ClNO2) are likewise reactive gases and vigorous halogenating agents.
Sources: en.wikipedia.org
== Further reading == Bryant, Alfred T. (1964). A History of the Zulu and Neighbouring Tribes. Cape Town: C. Struik. p. 157. Cana, Frank Richardson (1911). "Zululand" . Encyclopædia Britannica. Vol. 28 (11th ed.). pp. 1050–1055.
== History == While the practice of immunisation can be traced back to the 12th century, in which ancient Chinese at that time employed the technique of variolation to confer immunity to smallpox infection, the modern era of vaccination has a short history of around 200 years. It began with the invention of a vaccine by Edward Jenner in 1798 to eradicate smallpox by injecting relatively weaker cowpox virus into the human body. The middle of the 20th century marked the golden age of vaccine science. Rapid technological advancements during this period of time enabled scientists to cultivate cell culture under controlled environments in laboratories, subsequently giving rise to the production of vaccines against poliomyelitis, measles and various communicable diseases. Conjugated vaccines were also developed using immunologic markers including capsular polysaccharide and proteins. Creation of products targeting common illnesses successfully lowered infection-related mortality and reduced public healthcare burden. Emergence of genetic engineering techniques revolutionised the creation of vaccines. By the end of the 20th century, researchers had the ability to create recombinant vaccines apart from traditional whole-cell vaccine, for instance Hepatitis B vaccine, which uses the viral antigens to initiate immune responses.
=== Autonomic neuropathy === During hypoglycemia, the body normally releases epinephrine (more commonly known as adrenaline) and related substances. This serves two purposes: The β-effect of epinephrine is responsible for the palpitations and tremors, giving the patient warning that hypoglycemia is present. The β-effect of epinephrine also stimulates the liver to release glucose (gluconeogenesis and glycogenolysis). In other words, the epinephrine warns the patient that hypoglycemia is present and signals the liver to release glucose to reverse it. In the absence of epinephrine release, or when it is attenuated (reduced) during hypoglycemia, the patient may not be aware that his/her glucose level is low. This is termed 'hypoglycemic unawareness'. The problem is compounded since, in the absence of an appropriate epinephrine response, the usual responses of glycogenolysis and gluconeogenesis may also be lost or blunted. Since epinephrine release is a function of the autonomic nervous system, the presence of autonomic neuropathy (i.e., a damaged autonomic nervous system) will cause the epinephrine release in response to hypoglycemia to be lost or blunted. Unfortunately, damage to the autonomic nervous system in the form of autonomic neuropathy is a common complication of long-standing diabetes (especially type 1 diabetes), so the presence of hypoglycemic unawareness may be a sign of autonomic neuropathy, although the autonomic response to hypoglycemia is already impaired in patients with type 1 diabetes mellitus even in the absence of autonomic neuropathy.
The PLA is a component of the armed forces of China, which also includes the PAP, the reserves, and the militia. The armed forces are controlled by the CCP under the doctrine of "the Party commands the gun". The PLA and the PAP have the largest delegation in the National People's Congress (NPC), which are elected by servicemember election committees of top-level military subdivisions, including the PLA's theater commands and service branches. At the 14th National People's Congress; the joint delegation has 281 deputies—over 9% of the total—all of whom are CCP members.
aminoglycosides (gentamicin, amikacin, tobramycin, but not kanamycin) quinolones (ciprofloxacin, levofloxacin, but not moxifloxacin) cephalosporins (ceftazidime, cefepime, cefoperazone, cefpirome, ceftobiprole, but not cefuroxime, cefotaxime, or ceftriaxone) antipseudomonal penicillins: carboxypenicillins (carbenicillin and ticarcillin), and ureidopenicillins (mezlocillin, azlocillin, and piperacillin). P. aeruginosa is intrinsically resistant to all other penicillins. carbapenems (meropenem, imipenem, doripenem, but not ertapenem) polymyxins (polymyxin B and colistin) monobactams (aztreonam) As fluoroquinolones are one of the few antibiotic classes widely effective against P. aeruginosa, in some hospitals, their use is severely restricted to avoid the development of resistant strains. On the rare occasions where infection is superficial and limited (for example, ear infections or nail infections), topical gentamicin or colistin may be used. For pseudomonal wound infections, acetic acid with concentrations from 0.5% to 5% can be an effective bacteriostatic agent in eliminating the bacteria from the wound. Usually a sterile gauze soaked with acetic acid is placed on the wound after irrigation with normal saline. Dressing would be done once per day. Pseudomonas is usually eliminated in 90% of the cases after 10 to 14 days of treatment.
Sources: en.wikipedia.org
=== From titration curves === From the titration of protonatable group, one can read the so-called pKa1⁄2 which is equal to the pH value where the group is half-protonated (i.e. when 50% such groups would be protonated). The pKa1⁄2 is equal to the Henderson–Hasselbalch pKa (pKHHa) if the titration curve follows the Henderson–Hasselbalch equation. Most pKa calculation methods silently assume that all titration curves are Henderson–Hasselbalch shaped, and pKa values in pKa calculation programs are therefore often determined in this way. In the general case of multiple interacting protonatable sites, the pKa1⁄2 value is not thermodynamically meaningful. In contrast, the Henderson–Hasselbalch pKa value can be computed from the protonation free energy via
The efferent leg of the peripheral nervous system is responsible for conveying commands to the muscles and glands, and is ultimately responsible for voluntary movement. Nerves move muscles in response to voluntary and autonomic (involuntary) signals from the brain. Deep muscles, superficial muscles, muscles of the face and internal muscles all correspond with dedicated regions in the primary motor cortex of the brain, directly anterior to the central sulcus that divides the frontal and parietal lobes. In addition, muscles that react to reflexive nerve stimuli do not always send signals all the way to the brain. In this case, the signal from the afferent fiber does not reach the brain, but produces the reflexive movement by direct connections with the efferent nerves in the spine. However, the majority of muscle activity is volitional, and the result of complex interactions between various areas of the brain like the basal ganglia, thalamus, cerebellum, and other neuron groups in the midbrain and brain stem. Nerves that control skeletal muscles in mammals correspond with neuron groups along the primary motor cortex of the brain's cerebral cortex. Commands are routed through the basal ganglia and are modified by input from the cerebellum before being relayed through the pyramidal tract to the spinal cord and from there to the motor end plate at the muscles. Along the way, feedback, such as that of the extrapyramidal system contribute signals to influence muscle tone and response.
Further, due to the small size of available samples, the melting point of einsteinium was often deduced by observing the sample being heated inside an electron microscope. Thus, surface effects in small samples could reduce the melting point. The metal is trivalent and has a noticeably high volatility. In order to reduce the self-radiation damage, most measurements of solid einsteinium and its compounds are performed right after thermal annealing. Also, some compounds are studied under the atmosphere of the reductant gas, for example H2O+HCl for EsOCl so that the sample is partly regrown during its decomposition. Apart from the self-destruction of solid einsteinium and its compounds, other intrinsic difficulties in studying this element include scarcity—the most common 253Es isotope is available only once or twice a year in sub-milligram amounts—and self-contamination due to rapid conversion of einsteinium to berkelium and then to californium at a rate of about 3.3% per day:
As exciting and promising as Kermani's attempt to ground the belief in revelation in aesthesis and to understand the knowledge of God as a perception of the heart may be, this approach raises the question of how to deal with the sensory experiences of pain and the absence of God in the world. The abysses of suffering in our world —especially with this kind of aesthetic approach to the belief in revelation — compel us to ask how experiences of suffering and salvation, of horror and the beauty of God can be reconciled.
=== Droplet merging === As an existing droplet can be split to form discrete droplets using electrodes (see From an existing droplet), droplets can be merged into one droplet by electrodes as well. Utilizing the same concept applied for creating new droplets through splitting an existing droplet with electrodes, an aqueous droplet resting on an uncharged electrode can move towards a charged electrode where droplets will join and merge into one droplet. However, the merged droplet might not always form a circular shape even after the merging process is over due to surface tension. This problem can be solved by implementing a superhydrophobic surface between the droplets and the electrodes. Oil droplets can be merged in the same way as well, but oil droplets will move towards uncharged electrodes unlike aqueous droplets.
Sources: en.wikipedia.org
Yes. Lyophilization and freeze-drying are synonyms for the same vacuum-assisted sublimation process. The term lyophilization is more common in pharmaceutical and laboratory settings, while freeze-drying is widely used in food and general contexts.
Reduced pressure lowers the boiling point of water and allows ice to sublime below its triple point. Without sufficient vacuum, melting or boiling may occur instead of sublimation, which can damage the product structure.
Heat and mass transfer limit drying once the ice front recedes. The dried layer insulates the frozen core and resists vapor flow, so increasing shelf temperature too quickly can cause collapse or meltback.
Primary drying removes ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, often under the same vacuum. The two stages differ in the water state being removed.