If you have been reading about Sublimation and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-02-28. Where a claim depends on a specific study, the study is described rather than over-claimed.
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.
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.
After drying, a lyophilized product is usually sealed under vacuum or an inert gas to limit moisture and oxygen exposure. The container closure system matters because stoppers and seals can allow moisture ingress over time. Storage conditions are selected from stability studies that track potency, cake appearance, and reconstitution behavior. Many freeze-dried materials are kept at controlled room temperature, while some require refrigeration or protection from light.
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.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying; lyophilisation; cryodesiccation | Regional spelling and historical terms. |
| Primary drying pressure | 0.05-0.5 mbar (5-50 Pa) | Kept below the triple point of water; product-specific. |
| Shelf temperature range | -40 to +40 °C | Freezing, primary, and secondary stages use different set points. |
| Cycle duration | 12-72 hours | Depends on fill volume, formulation, and equipment. |
| Condenser temperature | -50 to -80 °C | Must remain below the product's ice temperature. |
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.
Freezing determines ice crystal structure and pore size, which affect drying speed and product uniformity. Rapid freezing creates small crystals, while slow freezing creates larger crystals and often faster sublimation. During primary drying, chamber pressure is held below the vapor pressure of ice, and shelf temperature supplies heat for sublimation. The ice front recedes, leaving a porous matrix. Thermal limits such as collapse and eutectic temperatures set safe boundaries for formulation. These limits vary with solute composition and concentration.
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.
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.
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.
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.
=== No development reported === 4-Chlorokynurenine (4-CL-KYN; 7-CL-KYNA; AV-101) – ionotropic glutamate NMDA receptor antagonist and 3-hydroxyanthranilate oxidase inhibitor [146] α-Synuclein picobody (a-syn-pico) – positron-emission tomography (PET) enhancer – diagnosis [147] A-86929 – dopamine D1 receptor agonist [148] AB-4166 – microbiome modulator [149] ACI-12589 – positron-emission tomography (PET) enhancer – diagnosis [150] Affitope-PD03 (PD03; PD03A) – α-synuclein inhibitor and immunostimulant [151] ANPD-002 (ANPD002) – dopaminergic cell replacement [152] AP-472 – metabotropic glutamate mGlu4 receptor positive allosteric modulator [153] Aplindore (DAB-452; palindore; SLS-006; WAY-DAB 452) – dopamine D2 receptor agonist [154] Armesocarb (MLR-1019) – atypical dopamine reuptake inhibitor (DRI) [155] Atuzaginstat (COR-388) – peptide hydrolase inhibitor [156] ATV:aSyn (ATV:α-synuclein; ATV:αSyn) – α-synuclein inhibitor [157] Autologous adipose derived mesenchymal stem cells - Hope Biosciences – cell replacement [158] AZ-001 – undefined mechanism of action [159] Beperminogene perplasmid (AMG-0001; Collategene; hepatocyte growth factor gene therapy) – gene transference and hepatocyte growth factor (HGF) expression stimulant [160] BTRX-246040 (LY-2940094) – nociceptin receptor (NOP) antagonist [161] Cannabidiol/tetrahydrocannabinol (CBD/THC; CanChew; MedChew; THC/CBD) – cannabinoid CB1 and CB2 receptor agonist and other actions [162] Carbidopa/levodopa (WD-1603) – combination of carbidopa (aromatic L-amino acid decarboxylase (AAAD) inhibitor) and levodopa (dopamine precursor) [163] Carbidopa/levodopa oral solution (EXN-32) – combination of carbidopa (aromatic L-amino acid decarboxylase (AAAD) inhibitor) and levodopa (dopamine precursor) [164] Ciforadenant (CPI-444, V-81444) – adenosine A2A receptor antagonist CM-4612 (CM-ADHD; CM-AT; CM-PK) – enzyme replacement and modulator [165] Crisdesalazine (AAD-2004) – microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor [166] CTx-GBA1 – gene transference [167] Cu(II)ATSM (copper(II)-ATSM; Cu-ATSM) – neuron modulator [168] Debamestrocel (autologous bone marrow derived mesenchymal stem cell therapy; NurOwn) – dopaminergic cell replacement [169] DNL-201 – leucine-rich repeat kinase 2 (LRRK2) inhibitor [170] Dopamine intranasal – non-selective dopamine receptor agonist [171] DX-0308 (DX-308) – retinoic acid metabolism modulator [172] Emrusolmin (anle-138b; TEV-56286) – α-synuclein inhibitor and protein aggregation inhibitor [173] ESB-1609 – sphingosine-1-phosphate (S1P) receptor agonist [174] ESB-5070 – leucine-rich repeat kinase 2 (LRRK2) inhibitor [175] F-14413 – α2-adrenergic receptor inverse agonist [176] FB-101 (1ST-102) – Bcr-Abl tyrosine kinase inhibitor [177] Fibroblast growth factor 1 (FGF-1) – fibroblast growth factor stimulant and angiogenesis-inducing agent [178] GO-101 – gene transference [179] GT-02329 – β-glucocerebrosidase (GCase) activator and/or chaperone [180] ISC-hpNSC (human parthenogenetic neural stem cells) – dopaminergic cell replacement [181] Itanapraced (CHF-5074; CSP-1103) – γ-secretase modulator and non-steroidal anti-inflammatory drug (NSAID) derivative lacking cyclooxygenase (COX) inhibition [182] Levodopa deuterated (deuterium-containing levodopa; SD-1077) – dopamine precursor and indirect non-selective dopamine receptor agonist [183] Liatermin (BVF-014; GDNF; glial-derived neutrotrophic factor; r-metHuGDNF) – neuron stimulant [184] Lu-AE-04621 (Lu-AE04621) – dopamine receptor agonist (prodrug of Lu-AA40326) [185] Masupirdine (SUVN-502; SUVN502) – serotonin 5-HT6 receptor antagonist [186] Mesocarb (MLR-1017) – atypical dopamine reuptake inhibitor (DRI) [187] MTK-458 – protein-serine-threonine kinase stimulant [188] NPT-200-11 (NPT200-11; UCB-1332) – α-synuclein inhibitor [189] NPT-520-34 (NPT520-34) – 1-phosphatidylinositol 3 kinase modulator and other actions [190] ODM-104 – catechol O-methyltransferase (COMT) inhibitor [191] OP-101 (dendrimer N-acetylcysteine) – various actions [192] OP-501 – catechol O-methyltransferase (COMT) inhibitor [193] Ordopidine (ACR-325) – low-affinity dopamine D2 receptor antagonist and dopaminergic stabilizer [194] PD-04 (a-Syn-PD-04; Affitope PD-04; PD04) – peptide vaccine against α-synuclein [195] Rasagiline – monoamine oxidase B (MAO-B) inhibitor [196] Rasagiline transdermal patch (TPU-002RA) – monoamine oxidase B (MAO-B) inhibitor [197] Research programme: adenosine A2A/A1 selective antagonists - Domain Therapeutics/CleveXel Pharma (CVXL-0069; DT-1133; DT0926; FP-0692; FP-1133) – adenosine A1 receptor antagonists and adenosine A2A receptor antagonists [198] Research programme: catalytic antioxidants - Aeolus Pharmaceuticals (AEOL-10113; AEOL-11207) – antioxidants [199] Research programme: central nervous system therapeutics - Delpor – undefined mechanism of action [200] Research programme: cGAS/STING antagonists - IFM Due – nucleotidyltransferase inhibitors [201] Research programme: COMT inhibitors - Avalo Therapeutics (AVTX-406; CERC-425; CERC-406) – catechol O-methyltransferase (COMT) inhibitors [202] Research programme: dopamine D1 receptor agonists - Takeda – dopamine D1 receptor agonists [203] Research programme: exosome therapeutics - ArunA Biomedical – undefined mechanism of action [204] Research programme: GPCR modulators - Nxera Pharma – various actions [205] Research programme: KEAP1 inhibitors - Keapstone Therapeutics – Kelch-like ECH-associated protein 1 (KEAP1) inhibitors [206] Research programme: long-acting neuropsychiatric therapeutics - Teva (NP-201; NP-202; risperidone/ropinirole implants) – various actions [207] Research programme: LRRK2 inhibitor - GlaxoSmithKline – leucine-rich repeat kinase 2 (LRRK2) inhibitors [208] Research programme: LRRK2 inhibitors - Novartis – leucine-rich repeat kinase 2 (LRRK2) inhibitors [209] Research programme: neurodegenerative disorder gene therapies - Denali Therapeutics (AAV-LF2; CNS-directed AAV-based gene therapies) – gene transference [210] Research programme: neurodegenerative disorders therapeutics - BioArctic Neuroscience (AD-0802; AD-1502; AD-2203; AE-1501; BAN-2203; BAN-2502; BAN2401 back-up) – various actions [211] Research programme: neurodegenerative disorder therapeutics - Celgene Corporation/Evotec (BMSxxx) – cell replacements [212] Research programme: neurodegenerative disease therapeutics - ProteoTech (DP-68; DP-74; PD-61-W3; PeptiClere; PTI-19; PTI-51; PTI-51-CH3; Synuclere; TauPro) – various actions [213] Research programme: neurological disorders therapeutics - Gloriana therapeutics (ECB-PD; ECT-PD; Meteorin; Ns-G34; NsG-0301; NsG-33) – glial cell line-derived neurotrophic factor modulators [214] Research programme: Parkinson's disease therapeutics - Alectos Therapeutics – glucocerebrosidase 2 (GBA2) protein inhibitor [215] Research programme: Parkinson's disease therapies - Zymes (co-Q10; coenzyme Q10; ubidecarenone) – antioxidants [216] Research programme: Parkinson's disease therapy - AbbVie – dopamine D2 and D3 receptor agonists [217] Research programme: positive allosteric modulators - Proximagen – various actions [218] Research programme: protective autoimmunity enhancer - Proneuron Biotechnologies (PN-277) – immunomodulators [219] Research programme: protein phosphatase 2A modulators - Signum Biosciences (SIG-1012; SIG-1106) – protein phosphatase 2A (PP2A) modulator [220] Research programme: small molecule therapeutics - Amathus Therapeutics – mitochondrial protein stimulants [221] Research programme: small molecule therapeutics - Aranda Pharma/Tarrex Biopharma (ADA-308; ADA-409; Backup; MDA-308; MDA-409) – androgen receptor antagonists [222] Research programme: transmembrane protein 175 agonists - AbbVie/Caraway Therapeutics – TMEM175 stimulants [223] Rotigotine controlled release (SER-214) – non-selective dopamine receptor agonist and other actions [224] S-32504 – dopamine D2 and D3 receptor agonist [225] SAGE-324 (BIIB-124) – GABAA receptor positive allosteric modulator and neurosteroid [226] Saracatinib (AZD-0530) – Src-family kinase inhibitor [227] Selegiline transdermal (Emsam) – monoamine oxidase B (MAO-B) inhibitor and other actions [228] Seridopidine (ACR343; ACR-343) – dopamine receptor modulator and so-called "dopaminergic stabilizer" [229] SLS-004 (LV-dCas9-DNMT3A) – gene therapy and α-synuclein expression inhibitor [230] Sonlicromanol (KH-176) – prostaglandin-E synthase inhibitor and reactive oxygen species modulator [231] SPN-803 (SPN803) – undefined mechanism of action [232] STEL-101 (AMA-101; STL-101) – undefined mechanism of action [233] UB-312 – immunostimulant [234] YKP-10461 (SKL-PD; YKP10461) – monoamine oxidase B (MAO-B) inhibitor [235] YTX-7739 – stearoyl-CoA desaturase inhibitor [236] Xenon (NBTX-001) – ionotropic glutamate NMDA receptor antagonist [237]
Following ISIL's successful Anbar campaign and June 2014 offensive, the Badr Organization mobilized and won a series of battles against ISIL, including the Liberation of Jurf Al Sakhr and the Lifting of the Siege of Amirli. In early February 2015, the group, operating from its base at Camp Ashraf, fought in Diyala Governorate against ISIL. Over 100 militia were killed in the fighting, including 25 in Al Mansouryah. Badr's leader, Hadi al-Amiri, said his militiamen were committed to the safety of Sunnis, but deep mutual suspicions remained in the light of recent sectarian killings and the suspicion that some Sunni tribes were allied with IS. A leaked US diplomatic cable cited sources alleging that Hadi al-Amiri had personally ordered attacks on Sunnis.
=== Venezuela === Colombia and neighbouring Venezuela have met regularly in the South American Championship, the Copa América and World Cup qualification. Colombia has historically held the superior head-to-head record, but the fixture has gained importance as Venezuela's national team became more competitive from the late 1990s. Venezuela's 1–0 victory in Barranquilla during 2006 World Cup qualification was regarded as a landmark result for the Venezuelan side. In 2026 World Cup qualification, Colombia won 1–0 in Barranquilla in September 2023 and 6–3 in Maturín in September 2025; the latter result eliminated Venezuela from contention for the CONMEBOL inter-confederation play-off place.
Sources: en.wikipedia.org
Research of arthrogryposis has shown that anything that inhibits normal joint movement before birth can result in joint contractures. Arthrogryposis could be caused by genetic and environmental factors. In principle: any factor that curtails fetal movement can result in congenital contractures. The exact causes of arthrogryposis are unknown.
=== Gluconeogenesis === Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis (see figure). For the breakdown of proteins, these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol, odd-chain fatty acids (although not even-chain fatty acids, see below); and from other parts of metabolism they include lactate from the Cori cycle. Under conditions of prolonged fasting, acetone derived from ketone bodies can also serve as a substrate, providing a pathway from fatty acids to glucose.
This result shattered the Centre Party's hopes of being indispensable for obtaining a majority in parliament. The party was now faced with two alternatives – either to persist in protesting and risk reprisals like Communists and Social Democrats, or to declare their loyal cooperation, in order to protect their members. As shown by subsequent events, though deeply uncomfortable with the new government, the party opted for the latter alternative.
Sources: en.wikipedia.org
Joseph Abram, Le Havre: Modern City, 2011 Nathalie Castetz, Le Havre, Seine Estuary, Paris, Héliopoles, 2012, ISBN 978-2-919006-10-6 Franck Godard and Olivier Bouteiller, Le Havre, Déclics, 2011, ISBN 978-2-84768-231-1 Unusual Le Havre, Renée Grimaud, Les beaux jours, 2012, ISBN 978-2-35179-101-1 Jean-François Massé, Le Havre, attached port, Acanthe, 2003, ISBN 2-84942-003-4 Tristan Gaston-Breton, Le Havre 1802–2002: Two centuries of economic adventure, Le Cherche midi, 2002, ISBN 2-7491-0028-3 E. Simon, A. Fiszlewicz, Le Havre: What an Estuary!, Petit à Petit, 2002, ISBN 2-914401-26-4 Madeleine Brocard, Atlas of the Estuary of the Seine, Rouen, Presses de l'université de Rouen, 1996 Emanuelle Real, The Industrial Landscape of Basse-Seine, Connaissance du patrimoine en Haute-Normandie, 2009, ISBN 2-910316-33-5, 264 pages Jacques Basile and Didier Guyot, Another Blue City, Editions Point de Vues, 2011, 120 pages, ISBN 978-2-915548-63-1
=== GPI-anchor === Bioinformatic analysis predicts the addition of a GPI-anchor on many AGPs. The early synthesis of the GPI moiety occurs on the ER cytoplasmic surface and subsequent assembly take place in the lumen of the ER. These include the assembly of tri-mannose (Man), galactose, non-N-acetylated glucosamine (GlcN) and ethanolamine phosphate to form the mature GPI moiety. AGPs undergo GPI-anchor addition while co-translationally migrating into the ER and these two processes finally converge. Subsequently, a transamidase complex simultaneously cleaves the core protein at the C-terminus when it recognizes the ω cleavage site and transfers the fully assembled GPI-anchor onto the amino acid residue at the C-terminus of the protein. These events occur prior to prolyl hydroxylation and glycosylation. The core glycan structure of GPI anchors is Man-α-1,2-Man-α-1,6-Man-α-1,4-GlcN-inositol (Man: mannose, GlcN: glucosaminyl), which is conserved in many eukaryotes. The only plant GPI anchor structure characterized to date is the GPI-anchored AGP from Pyrus communis suspension-cultured cells. This showed a partially modified glycan moiety compared to previously characterized GPI anchors as it contained β-1,4-Gal. The GPI anchor synthesis and protein assembly pathway is proposed to be conserved in mammals and plants. The integration of a GPI-anchor enables the attachment of the protein to the membrane of the ER transiting to the GA leading to secretion to the outer leaflet of the plasma membrane facing the wall.
(Stone, 2017) Depression is a major problem globally, affecting an estimated 4.4 percent of the world population in 2017, roughly equivalent to 300 million people. The depression is multifactorial and has been on the increase due to societal pressure, genetic association and increase in use of drugs (Zhang et al. 2016). incorporation of nursing in management of depression may seem important in that nursing hold a pivotal role in health care delivery where they are they are the health practitioners that have been trained to be versatile from clinical to psychological care Their incorporation shared decision making in treating depression may be important as nurses are known to have the best interpersonal relationship with the patients thus a better collaborative model can be achieved due to this fact (Williams et al. 2016). With this in mind, the nurses may serve to administer drugs in management, prepare and maintain the patient's records, interaction with other care staff to achieve optimum care, and organizing therapy sessions (Lu et al. 2019). Kathleen Walsh, 2017, recognizes that Dr. Velligan stated that SDM is of importance in demonstrating patient preferences in decision making when there is no clear approach to treatment. In addition, numerous tools can be used to make the decision making the process easier these include the Controlled Preferences Scale that informs clinicians on how to actively involve patients.
The Roman author Vitruvius reported the health dangers of lead and modern writers have suggested that lead poisoning played a major role in the decline of the Roman Empire. Other researchers have criticized such claims, pointing out, for instance, that not all abdominal pain is caused by lead poisoning. According to archaeological research, Roman lead pipes increased lead levels in tap water but such an effect was "unlikely to have been truly harmful". When lead poisoning did occur, victims were called "saturnine", dark and cynical, after the ghoulish father of the gods, Saturn. By association, lead was considered the father of all metals. Its status in Roman society was low as it was readily available and cheap.
Sources: en.wikipedia.org
Simple drying usually removes water by evaporation from a liquid or solid, often with heat. Lyophilization first freezes the material and then removes ice by sublimation under vacuum. This avoids prolonged exposure to liquid water and high temperatures.
Reduced pressure lowers the boiling point of water and allows ice to sublime at temperatures below freezing. It also helps remove water vapor from the product toward the condenser. The exact pressure is chosen to stay below the triple point of water.
No. Materials with low solids content or high volatile solvents may form weak or collapsed cakes. Some proteins and cells require stabilizers to survive freezing and drying stresses. Feasibility depends on formulation and process design.
Sealed vials or containers should be kept at the temperature specified by stability data, often controlled room temperature or 2–8 °C. Moisture and oxygen barriers are important because both can degrade sensitive materials. Opened containers may need immediate use or protection from ambient humidity.