Everything below concerns residual moisture. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-10-12. Where a claim depends on a specific study, the study is described rather than over-claimed.
Lyophilization, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
The process relies on the phase diagram of water, where the triple point marks the conditions at which ice, liquid water, and vapor coexist. By maintaining pressure below this point, typically around 0.01 to 0.1 millibar, sublimation becomes the dominant mechanism. Formulations often include excipients such as sugars or polymers that act as lyoprotectants and bulking agents. These additives help preserve the structure of the active ingredient and prevent collapse during drying. The choice of excipient and freezing rate influences the final cake morphology and stability.
Quality control for lyophilized products includes appearance, cake structure, reconstitution time, pH, residual moisture, and potency. Residual moisture is a key attribute because excess water can reduce stability, while excessively low moisture may cause structural changes or aggregation in some systems. Stability studies compare real-time and accelerated conditions to estimate shelf life. Analytical methods must be validated for the specific matrix, container, and moisture range. Sterility and container integrity are also monitored for sterile products.
Handling practices aim to prevent moisture ingress and mechanical damage. Vials should remain stoppered and crimped until use, and reconstitution should follow the labeled diluent and volume. Shipping may involve temperature-controlled containers and desiccants, but direct contact between desiccant and product is avoided. Regulatory guidance expects documented storage conditions, excursion assessments, and stability commitments. Open questions remain about how best to predict long-term stability from short accelerated studies for every formulation class.
After lyophilization, the product is usually a porous cake or powder with a large internal surface area. This structure can absorb moisture quickly if exposed to humid air, so vials are sealed under vacuum or an inert gas. Moisture uptake may lower the glass transition temperature of the dried matrix and accelerate chemical or physical degradation. Storage conditions therefore depend on the formulation, container, and intended shelf life. Some products remain stable at room temperature, while others require refrigeration or freezing.
| Property | Value | Notes |
|---|---|---|
| Common name | Freeze-drying | Lyophilization is the technical synonym. |
| Typical chamber pressure | 0.01–0.1 mbar | Below the triple point of water. |
| Primary drying temperature | −40 to −10 °C | Depends on formulation and equipment. |
| Residual moisture | 1–5% | Target for many pharmaceutical products. |
| Typical equipment | Vacuum freeze-dryer | Includes drying chamber and condenser. |
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.
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.
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 depend on the formulation and the intended shelf life. Many pharmaceutical and biological freeze-dried products are kept at 2–8 °C, while some stable foods and reagents tolerate room temperature. Others require −20 °C or colder to slow chemical degradation or aggregation. Protection from light and oxygen is common because oxidation can continue in the dry state. Stability studies usually monitor potency, appearance, moisture, and reconstitution time over months or years. Predictions from accelerated studies are useful but may not fully capture real-time changes.
Quality control for freeze-dried lots combines visual inspection with instrumental tests. Cake appearance, color, and shrinkage are recorded against a reference, while residual moisture is measured by Karl Fischer titration or loss on drying. Thermal analysis can reveal phase transitions and crystallization events, and X-ray diffraction distinguishes amorphous from crystalline solids. Microbiological tests and container closure integrity checks are also routine for sterile products. Analytical methods must be validated for the matrix, because excipients and low moisture can affect accuracy. Open questions include how best to predict long-term stability from short-term data.
=== Definition === The definition of chemistry has changed over time, as new discoveries and theories add to the functionality of the science. The term "chymistry", in the view of noted scientist Robert Boyle in 1661, meant the subject of the material principles of mixed bodies. In 1663, the chemist Christopher Glaser described "chymistry" as a scientific art, by which one learns to dissolve bodies, and draw from them the different substances on their composition, and how to unite them again, and exalt them to a higher perfection. The 1730 definition of the word "chemistry", as used by Georg Ernst Stahl, meant the art of resolving mixed, compound, or aggregate bodies into their principles; and of composing such bodies from those principles. In 1837, Jean-Baptiste Dumas considered the word "chemistry" to refer to the science concerned with the laws and effects of molecular forces. This definition further evolved until, in 1947, it came to mean the science of substances: their structure, their properties, and the reactions that change them into other substances—a characterization accepted by Linus Pauling. More recently, in 1998, Professor Raymond Chang broadened the definition of "chemistry" to mean the study of matter and the changes it undergoes.
== Further reading == Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Administration of radioactive substances advisory committee. March 2006. Produced by the Health Protection Agency. Malabsorption. In: The Merck Manual of Geriatrics, chapter 111. Leukoscan summary of product characteristics (Tc99m-Sulesomab). Schwochau, Klaus. Technetium. Wiley-VCH (2000). ISBN 3-527-29496-1
Physical-chemical testing; Toxicity studies; Mutagenicity studies; Environmental toxicity studies on aquatic and terrestrial organisms; Studies on behavior in water, soil, and air; bioaccumulation; Studies to determine pesticide residues in food or animal feedstuffs; Studies on effects on mesocosms and natural ecosystems; Analytical and clinical chemistry testing. Safety testing data must be submitted to regulatory authorities for product marketing authorization. During the review process, the submitted data undergoes verification to ensure compliance with GLP standards. Additionally, the GLP compliance status of the testing facility where the study was conducted is assessed by referring to inspection information from national GLP compliance monitoring programs. OECD member countries where non-clinical health and environmental safety testing follows the OECD Principles of Good Laboratory Practice (GLP) have established national GLP Compliance Monitoring Programs (CMP) responsible for overseeing GLP compliance of test facilities within their jurisdictions. These CMPs verify GLP compliance through inspections of test facilities and audits of GLP studies. Test facilities that undergo periodic inspections by a CMP and are found to operate in accordance with GLP principles are recognized as GLP compliant. In OECD-member countries, testing facilities seeking recognition as GLP compliant can apply to the national CMP. The CMP then conducts inspections to assess if the test facility adheres to the OECD Principles of GLP.
Some proteins are synthesized by nonribosomal peptide synthetases, which can be big protein complexes, each specializing in synthesizing only one type of peptide. Nonribosomal peptides often have cyclic or branched structures and can contain non-proteinogenic amino acids – both of these factors differentiate them from ribosome synthesized proteins. An example of nonribosomal peptides are some of the antibiotics.
Sources: en.wikipedia.org
Before the widespread use of a vaccine against measles, rates of disease were so high that infection was felt to be "as inevitable as death and taxes." Reported cases of measles in the United States fell from hundreds of thousands to tens of thousands per year following introduction of the vaccine in 1963. Increasing uptake of the vaccine following outbreaks in 1971, and 1977, brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. Fewer than 200 cases have been reported in the US each year between 1997 and 2013, and the disease is no longer considered endemic there. The benefit of measles vaccination in preventing illness, disability, and death has been well documented. The first 20 years of licensed measles vaccination in the US prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability, and 5,200 deaths. During 1999–2004, a strategy led by the World Health Organization and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. Between 2000 and 2018, measles vaccination resulted in a 73% decrease in deaths from the disease. Measles is common in many areas of the world. Although it was declared eliminated from the US in 2000, high rates of vaccination and good communication with people who refuse vaccination are needed to prevent outbreaks and sustain the elimination of measles in the US.
Ir-catalyzed Lys and N-terminus (reductive) alkylation Imines formed from the condensation of aldehydes with lysines or the N-terminus can be reduced efficient by a water-stable [Cp*Ir(bipy)(H2O)]SO4 complex in the presence of formate ions (serving as the hydride source). The reaction happens readily under physiologically relevant conditions and results in high conversion for various aromatic aldehydes.
=== Solution === The key to solving these equations in real devices is whenever possible to select regions in which most of the mechanisms are negligible so that the equations reduce to a much simpler form.
Treatment of hypocalcaemia – hypoparathyroidism, osteomalacia (adults), rickets (infants, children), renal osteodystrophy, chronic kidney disease Treatment of osteoporosis Prevention of corticosteroid-induced osteoporosis Calcitriol has been used in an ointment for the treatment of psoriasis, although the vitamin D analogue calcipotriol (calcipotriene) is more commonly used. Calcitriol has also been given by mouth for the treatment of psoriasis and psoriatic arthritis. Research on the noncalcemic actions of calcitriol and other VDR-ligand analogs and their possible therapeutic applications has been reviewed.
== Prevention == Methods in preventing amputation, limb-sparing techniques, depend on the problems that might cause amputations to be necessary. Chronic infections, often caused by diabetes or decubitus ulcers in bedridden patients, are common causes of infections that lead to gangrene, which, when widespread, necessitates amputation. There are two key challenges: first, many patients have impaired circulation in their extremities, and second, they have difficulty curing infections in limbs with poor blood circulation. Crush injuries where there is extensive tissue damage and poor circulation also benefit from hyperbaric oxygen therapy (HBOT). The high level of oxygenation and revascularization speed up recovery times and prevent infections. A study found that the patented method called Circulator Boot achieved significant results in prevention of amputation in patients with diabetes and arteriosclerosis. Another study found it also effective for healing limb ulcers caused by peripheral vascular disease. The boot checks the heart rhythm and compresses the limb between heartbeats; the compression helps cure the wounds in the walls of veins and arteries, and helps to push the blood back to the heart. For victims of trauma, advances in microsurgery in the 1970s have made replantation of severed body parts possible. The establishment of laws, rules, and guidelines, and the employment of modern equipment help protect people from traumatic amputations.
Sources: en.wikipedia.org
Haptophytes are similar and closely related to cryptophytes or heterokontophytes. Their chloroplasts lack a nucleomorph, their thylakoids are in stacks of three, and they synthesize chrysolaminarin sugar, which are stored in granules completely outside of the chloroplast, in the cytoplasm of the haptophyte.
== Molecular and crystal structure == The structure of the molecule of urea is O=C(−NH2)2. The urea molecule is planar when in a solid crystal because of sp2 hybridization of the N orbitals. It is non-planar with C2 symmetry when in the gas phase or in aqueous solution, with C−N−H and H−N−H bond angles that are intermediate between the trigonal planar angle of 120° and the tetrahedral angle of 109.5°. In solid urea, the oxygen center is engaged in two N−H−O hydrogen bonds. The resulting hydrogen-bond network is probably established at the cost of efficient molecular packing: The structure is quite open, the ribbons forming tunnels with square cross-section. The carbon in urea is described as sp2 hybridized, the C−N bonds have significant double bond character, and the carbonyl oxygen is relatively basic. Urea's high aqueous solubility reflects its ability to engage in extensive hydrogen bonding with water. By virtue of its tendency to form porous frameworks, urea has the ability to trap many organic compounds. In these so-called clathrates, the organic "guest" molecules are held in channels formed by interpenetrating helices composed of hydrogen-bonded urea molecules. In this way, urea-clathrates have been well investigated for separations.
=== Applications in cementitious materials === Molecular dynamics (MD) simulations have also been increasingly applied in cement and concrete research to investigate the nanoscale mechanical behavior and structural characteristics of hydration products. In particular, MD has been used to estimate the elastic properties of major clinker phases (C3S, C2S, C3A, and C4AF) and to evaluate the performance of different force fields in predicting their bulk, shear, and Young's moduli. Further studies have focused on calcium silicate hydrate (C–S–H) gel, which constitutes approximately 50–70% of hydrated cement paste. Using MD and Monte Carlo simulations, the influence of water content, Ca/Si ratio, and structural defects on the mechanical properties and stiffness of C–S–H have been explored in detail, revealing that increasing water content or Ca/Si ratio generally decreases the Young's modulus of the gel. Such nanoscale insights contribute to multiscale modeling frameworks that link atomic-scale properties of cement hydrates to the macroscopic performance of concrete, enabling the design of low-clinker, high-performance, and more sustainable cementitious materials.
Orthopoxviruses and some other nucleocytoplasmic large DNA viruses synthesize RNA using a virally encoded multi-subunit RNAP. They are most similar to eukaryotic RNAPs, with some subunits minified or removed. Exactly which RNAP they are most similar to is a topic of debate. Most other viruses that synthesize RNA use unrelated mechanics. Many viruses use a single-subunit DNA-dependent RNAP (ssRNAP) that is structurally and mechanistically related to the single-subunit RNAP of eukaryotic chloroplasts (RpoT) and mitochondria (POLRMT) and, more distantly, to DNA polymerases and reverse transcriptases. Perhaps the most widely studied such single-subunit RNAP is bacteriophage T7 RNA polymerase. ssRNAPs cannot proofread. B. subtilis prophage SPβ uses YonO, a homolog of the β+β′ subunits of msRNAPs to form a monomeric (both barrels on the same chain) RNAP distinct from the usual "right hand" ssRNAP. It probably diverged very long ago from the canonical five-unit msRNAP, before the time of the last universal common ancestor. Other viruses use an RNA-dependent RNAP (an RNAP that employs RNA as a template instead of DNA). This occurs in negative strand RNA viruses and dsRNA viruses, both of which exist for a portion of their life cycle as double-stranded RNA. However, some positive strand RNA viruses, such as poliovirus, also contain RNA-dependent RNAP.
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate water from a material, while lyophilization freezes the material and removes water by sublimation under vacuum. This avoids the liquid phase and reduces thermal damage to sensitive substances. The result is a porous cake that reconstitutes quickly.
A vacuum lowers the pressure below the triple point of water, allowing ice to sublimate directly into vapor without melting. It also removes water vapor from the product chamber and speeds up the drying process. Without vacuum, the ice would melt rather than sublimate.
Not all substances are suitable for lyophilization. Materials must form a stable frozen matrix and tolerate freezing and low pressure. Some small molecules, oils, or volatile compounds may not form a proper cake or may be lost during processing.
Collapse occurs when the product temperature rises above its collapse or eutectic temperature during drying. The frozen matrix loses structure, producing a shrunken or melted appearance. This can slow reconstitution and may affect stability.