Primary drying raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
Reviewed 2025-09-17. Anything still debated is marked as such rather than presented as settled.
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.
Analytical methods for lyophilized materials include X-ray diffraction for crystallinity, differential scanning calorimetry for thermal transitions, and scanning electron microscopy for pore morphology. Moisture sorption analysis shows how the cake responds to humidity. These methods help distinguish amorphous from crystalline states and detect phase changes. Open questions remain about how pore structure changes during long-term storage and how best to predict collapse under varied conditions. Comparisons across studies are complicated by differences in formulation, cycle, and storage history.
Quality control for lyophilized products focuses on appearance, moisture level, reconstitution time, and structural integrity. A cake should be uniform, intact, and free of meltback or collapse. Moisture level is measured by Karl Fischer titration or thermogravimetric analysis. Reconstitution time reflects pore structure and formulation. Visual inspection and vial integrity checks detect cracks, stopper defects, or particulate matter. These checks are often performed on samples from each batch. They help confirm that the drying cycle performed as intended.
Storage stability depends on water content, oxygen exposure, and temperature. Lyophilized solids are hygroscopic and can absorb water if exposed to humid air. Vials are usually sealed under vacuum or inert gas with rubber stoppers and aluminum crimps. Storage temperatures range from room temperature to refrigerated or frozen conditions depending on the material. Stability studies track potency, moisture, and physical form over time. Accelerated conditions can reveal sensitivity but may not predict long-term behavior.
| Property | Value | Notes |
|---|---|---|
| Process name | Lyophilization or freeze-drying | Both terms appear in technical standards and literature. |
| Phase transition | Sublimation | Solid ice becomes vapor without a liquid step. |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product temperature and equipment. |
| Typical product temperature | -40 °C to -10 °C | Measured during primary drying; formulation sets limits. |
| Water content after drying | 0.5-3% w/w | Target varies by material and stability needs. |
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.
Freeze-dried materials are hygroscopic to varying degrees and can take up moisture after drying. Storage therefore often uses sealed glass vials, rubber stoppers, and crimp seals to limit contact with ambient humidity. A desiccant may be included for moisture-sensitive products, although it is not universal. Controlled room temperature is sufficient for many lyophilizates, while others require refrigeration or freezing. Moisture ingress remains a primary cause of cake collapse, chemical degradation, and loss of reconstitution performance.
Quality assessment of a lyophilized product includes cake appearance, residual moisture, reconstitution time, and container closure integrity. A uniform, porous cake suggests that freezing and drying stayed within the formulation's design space. Cracks, shrinkage, meltback, or a glassy film can indicate thermal abuse or a formulation problem. Analysts also test for subvisible particles and sterility when the product requires those specifications. Visual inspection alone cannot confirm biological activity or chemical stability, so it is combined with analytical methods.
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.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
== Contribution, awards and achievements == He was awarded the Fellowship of Rockefeller Foundation Fellow in USA during 1960–61; Commonwealth Medical Fellowship and then Wellcome Research Fellowship in England during the 1970s. In London at the National Institute for Medical Research, he worked on mechanism of action of Pyrogen and in the field of thermoregulation, with Wilhelm Feldberg (1900–1993), a German-British-Jewish pharmacologist and biologist. Wilhelm Feldberg assisted many research workers who came to England as a part of their Commonwealth Medical Fellowship and Wellcome Research Fellowship. Under these Fellowships, Saxena and Feldberg published many papers during the 1970s. In total, Saxena has approximately 145 published research papers. He wrote Hospital Formulary in 1969 and a book-cum-manual for practical pharmacy and experimental pharmacology laboratory. He had been founding member of many academic bodies such Indian Pharmacological Society, Association of Physiologists and Pharmacologists of India, Indian Medical Association, Indian Academy of Neurosciences and Indian Association for the Advancement of Medical Education in India. Indian National Science Academy (INSA) elected him Fellow (FNA) in 1987.
Recent advancements on the nanoscale such as devices that fabricate both spherical and non-spherical droplets that are ultrafast and homogeneous mixed are being produced for large scale production of powdered particles in industrial applications. Monodispersed nanoparticles are also of great interest in catalyst fabrication. Many heterogeneous catalytic systems efficiencies rely on high surface areas of transition metal particles. Microfluidic techniques have been used to fabricate gold nanoparticles through the interfacial interaction of droplets containing gold chloride, hexane, and a reducing agent with a surrounding aqueous phase. This process can also control both the size and shape of nanoparticles/nanosheets with precision and high throughput compared to other methods such as physical vapor deposition. The use of droplets containing various materials such as silica or transition metals such as gold flowed through an immiscible oil phase has been shown to be effective in controlling both size of nanoparticles as well as pore size, which allows for design of efficient absorptive gas capture devices and heterogeneous catalysts. Monodispersed nanoparticles of gold and silver have been synthesized using gold and silver chloride droplets dosed with a reducing agent to cleave metal-ligand bonds, leading to the agglomeration of monodispersed metal nanoparticles which can be easily filtered out of solution.
=== European Union === The European Union defines a VOC as "any organic compound as well as the fraction of creosote, having at 293.15 K a vapour pressure of 0.01 kPa or more, or having a corresponding volatility under the particular conditions of use;". The VOC Solvents Emissions Directive was the main policy instrument for the reduction of industrial emissions of volatile organic compounds (VOCs) in the European Union. It covers a wide range of solvent-using activities, e.g. printing, surface cleaning, vehicle coating, dry cleaning and manufacture of footwear and pharmaceutical products. The VOC Solvents Emissions Directive requires installations in which such activities are applied to comply either with the emission limit values set out in the Directive or with the requirements of the so-called reduction scheme. Article 13 of The Paints Directive, approved in 2004, amended the original VOC Solvents Emissions Directive and limits the use of organic solvents in decorative paints and varnishes and in vehicle finishing products. The Paints Directive sets out maximum VOC content limit values for paints and varnishes in certain applications. The Solvents Emissions Directive was replaced by the Industrial Emissions Directive from 2013.
Materials science is an interdisciplinary field concerned with understanding the relationships between the structure of materials and their properties and using this knowledge to design materials for specific applications. The internal structure of a material—from atomic arrangements to microscopic features—strongly influences its mechanical, electrical, thermal, and optical behavior. In engineering practice, materials science and engineering are often described through the processing–structure–properties–performance paradigm, in which processing determines structure, structure determines properties, and properties ultimately control the performance of a material in service. The intellectual origins of materials science stem from the Age of Enlightenment, when researchers began to use analytical thinking from chemistry, physics, and engineering to understand ancient, phenomenological observations in metallurgy and mineralogy. Materials science still incorporates elements of physics, chemistry, and engineering. As such, the field was long considered by academic institutions as a sub-field of these related fields. Beginning in the 1940s, materials science began to be more widely recognized as a specific and distinct field of science and engineering, and major technical universities around the world created dedicated schools for its study. By studying how the history of a material (processing) influences its structure, properties, and performance, materials scientists have made many contributions to new technologies in biomaterials, metallurgy, and nanotechnology.
In modern-day 21st century, medicine has evolved to involve past treatments such as leech therapy, as well as advancing wound prevention and the treatment. A large part of wound care is wound treatment. This involves promoting healing, preventing infections, and getting rid of an already existent infection. Deciding on a treatment depends on the type of wound that a person has sustained. Varying from infections to burns, wound care is a priority in saving the limb, extremity, or life of a person. In a hospital or medical care setting, more severe wounds like diabetic ulcers, decubitus ulcers, and burns require sterile or clean (depending on the severity of the wound) dressings and wound care. The types of wound dressing include: dry dressings, wet-to-dry dressings, chemical-impregnated dressings, foam dressings, alginate dressings, hydrofiber dressings, transparent film dressings, hydrogel dressings, and hydrocolloid dressings. All of the listed dressing types require different materials to complete the dressing.
Sources: en.wikipedia.org
==== Pharmacokinetics ==== Nabilone can be readily absorbed from the small intestine into the systemic circulation. The rate and extent of absorption of nabilone are not affected by food intake. It takes around 2 hours to reach its highest concentration in blood. It is distributed extensively and quickly in various body tissues including liver where it is rapidly metabolised into several active metabolites. CYP450 enzymes may also be involved in some of its metabolism. Nabilone is mainly excreted with faeces.
== Awards and honors == 2023- Women's Empowerment Influencer Award Icahn School of Medicine at Mount Sinai 2017 – Elected Fellow of the American Society for Cell Biology 2015 – Senior Leadership Award of the Women in Cell Biology of the American Society for Cell Biology, named the Sandra K. Masur Leadership Award 2008 – Jacobi Medallion, Mount Sinai Alumni Association 2007 – Rosalind Franklin Society Invited Member of Founding Board 2001 Women in Medicine Silver Achievement Award, Association of American Medical Colleges 1997 Outstanding Woman Scientist – Association for Women in Science, Metropolitan New York Chapter 1997 Lew R. Wasserman Merit Award 1996 Outstanding Faculty Achievement Award 1978 Brotherhood Education Award, Conference of Christians and Jews
== External links == Media related to Coups d'état at Wikimedia Commons Quotations related to Coup d'état at Wikiquote The dictionary definition of coup d'état at Wiktionary John J. Chin, David B. Carter & Joseph G. Wright. Dataset on all military and non-military coup attempts in the world since 1946. Powell, Jonathan & Clayton Thyne. Global Instances of Coups from 1950–Present via Archive.org.
=== Discontinued === 2-BUMP – monoamine oxidase B (MAO-B) inhibitor [238] A-77636 – dopamine D1 receptor agonist [239] Acamprosate/baclofen (PXT-864) – combination of acamprosate (various actions) and baclofen (GABAB receptor agonist) [240] Adrogolide (ABT-431; DAS-431; A-86929 O,O′-diacetate) – dopamine D1 receptor agonist (prodrug of A-86929) [241] AP-001 – various actions [242] Apomorphine inhalation (VR-004; VR-040; VR-400) – non-selective dopamine receptor agonist and other actions [243] Apomorphine intranasal – non-selective dopamine receptor agonist and other actions [244] Apomorphine subcutaneous (ND-0701) – non-selective dopamine receptor agonist and other actions [245] Apomorphine transdermal patch – non-selective dopamine receptor agonist and other actions [246] Arimoclomol (BRX-345; Miplyffa; OR-01; OR-04) – undefined mechanism of action [247] Arundic acid (Arocyte Injection; Cereact Capsule; MK-0724; ONO-2506; Proglia) – various actions [248] Atomoxetine (LY-139603; Strattera; Tomoxetine) – norepinephrine reuptake inhibitor (NRI) [249] AVE-8112 (AVE8112; AVE-8112A) – phosphodiesterase PDE4 inhibitor [250] AX-201 (AX201) – nerve growth factor (NGF) stimulant [251] Bifeprunox (DU-127090) – serotonin 5-HT1A receptor agonist and dopamine D2 receptor agonist [252] BP-897 – dopamine D3 receptor agonist [253] Carbidopa/levodopa (AP-09004; AP-CD/LD) – combination of carbidopa (aromatic L-amino acid decarboxylase (AAAD) inhibitor) and levodopa (dopamine precursor) [254] CEP-1347 (KT-7515) – mitogen-activated protein kinase inhibitor and mixed-lineage kinase inhibitor [255] CERE-120 (AAV-NRTN; AAV-NTN; AAV2-neurturin; AAV2-NTN; neurturin gene therapy) – gene therapy, nerve tissue protein modulator, and neurturin agonist [256] Cinpanemab (BIIB-054) – monoclonal antibody against α-synuclein [257] CVXL-0107 – glutamate release inhibitor [258] Dactolisib (BEZ-235; NVP-BEZ-235; NVP-BEZ235-ANA; NVP-BEZ235-NX; RTB-101) – 1-phosphatidylinositol 3 kinase inhibitor and mTOR inhibitor [259] Davunetide intranasal (AL-108; NAP; NAPVSIPQ) – various actions [260] Dihydrexidine (DAR-0100) – dopamine D1 receptor agonist [261] Dihydrexidine (IP-202) – dopamine D1 and D5 receptor agonist [262] DNS-7801 – undefined mechanism of action [263] Embryonic neural cell therapy-Parkinson's Disease - CellFactors (Parkinson's disease cell therapy) – dopaminergic cell replacement [264] Emlenoflast (inzomelid; IZD-174; MCC-7840) – NLR family pyrin domain containing 3 (NLRP3) inhibitor [265] Entacapone (Comtan; Comtess; OR-611) – catechol O-methyltransferase (COMT) inhibitor [266] Ethyl eicosapentaenoic acid (AMR-101; Ethyl-EPA; LAX-101; Miraxion; Vascepa; Vazkepa) – various actions [267] Etrabamine (14-839JL; JL-14839) – dopamine D2 receptor agonist [268] Ezaladcigene resoparvovec (AAV-AADC; AV-201; GZ-404477; NBIb-1817) – gene transference and aromatic-L-amino-acid decarboxylase (AAAD) replacement [269] Fipamezole (BVF-025; JP-1730) – α2-adrenergic receptor antagonist [270] Florbenazine F18 (18F-DTBZ; 18F-AV-133; 18F-FP-dihydrotatetrabenazine; AV-133) – vesticular monoamine transporter 2 (VMAT2) inhibitor and radiopharmaceutical – diagnosis [271] Foliglurax (PXT-2331; PXT002331) – metabotropic glutamate mGlu4 receptor positive allosteric modulator [272] FRM-0334 (EVP-0334) – class I and class II histone deacetylase inhibitor [273] GYKI-52895 – dopamine reuptake inhibitor (DRI) [274] Levetiracetam (Keppra; L-059; SIB-S1; UCB-059; UCB-22059; UCB-L059) – synaptic vesicle glycoprotein 2A (SV2A) modulator [275] Lu-AA47070 (LU-AA-47070) – adenosine A2A receptor antagonist [276] Methylthioninium chloride (MTC; methylene blue; TRx-0014; TRx-014) – various actions [277] Naxagolide (L-647339) – dopamine D2 and D3 receptor agonist [278] Nebicapone (BIA-3202) – catechol O-methyltransferase (COMT) inhibitor [279] Nitecapone (OR-462) – catechol O-methyltransferase (COMT) inhibitor Nitisinone (NTBC; Orfadin; SC-0735; SYN-118) – 4-hydroxyphenylpyruvate dioxygenase inhibitor and dopamine release stimulant [280] NPT-088 (NPT088) – immunoglobulin fusion general amyloid interaction motif (GAIM) based dimer [281] NPT-189 (NPT189) – immunoglobulin fusion protein [282] NW-1048 – monoamine oxidase B (MAO-B) inhibitor [283] NYX-458 – ionotropic glutamate NMDA receptor positive allosteric modulator [284] ODM-103 – catechol O-methyltransferase (COMT) inhibitor [285] Omigapil (CGP-3466; SNT-317; TCH-346) – glyceraldehyde 3 phosphate dehydrogenase (GAPDH) inhibitor [286] OPM-201 (S-221237) – leucine-rich repeat kinase 2 (LRRK2) inhibitor [287] OSU-6162 (OSU6162; PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT2A receptor partial agonist (non-hallucinogenic), dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer") [288] Paliroden (SR-57667; SR-57667B) – nerve growth factor (NGF) stimulant [289] Pardoprunox (SLV-308; SME-308) – dopamine D2 and D3 receptor partial agonist, serotonin 5-HT1A receptor full agonist, and other actions [290] Parkinson's disease gene therapy - Oxford BioMedica (AXO Lenti PD; OXB-101; OXB-102; ProSavin) – gene transference [291] Pegipanermin (DN-TNF; INB-03; LIVNate™; Quellor™; soluble tumour necrosis factor inhibitor; XENP1595; XENP345; XPro 1595; XPro595; XProTM) – tumour necrosis factor alpha (TNFα) inhibitor and immunostimulant [292] PF-06412562 (CVL-562) – dopamine D1 and D5 receptor partial agonist [293] Piclozotan (SUN-4057; SUN-N-4057) – serotonin 5-HT1A receptor agonist – dyskinesia in Parkinson's disease [294] Preclamol ((–)-3-PPP) – dopamine D2 receptor partial agonist [295] Preladenant (MK-3814; privadenant; SCH-420814) – adenosine A2A receptor antagonist [296] Proxison – synthetic flavonoid-based antioxidant [297] Quinelorane (LY-163502) – dopamine D2 receptor agonist [298] Raseglurant (ADX-10059) – metabotropic glutamate mGlu5 receptor negative allosteric modulator [299] Razpipadon (CVL-871; PF-6669571; PF-06669571; PW-0464) – dopamine D1 receptor agonist [300] Renzapride (ATL-1251; AZM-112; BRL-24924) – serotonin 5-HT3 receptor antagonist and serotonin 5-HT4 receptor agonist [301] Research programme: Alzheimer's and Parkinson's disease diagnostic agents - Bayer HealthCare Pharmaceuticals/TauRx – undefined mechanism of action – diagnosis [302] Research programme: AMC therapeutics - Animuscure – undefined mechanism of action [303] Research programme: Ig fusion GAIM dimers - Proclara Biosciences (NPT-288; NPT-007; NPT-014; NPT-289) – various actions [304] Research programme: Parkinson's disease therapeutics - Araclon Biotech (AB-03) – undefined mechanism of action [305] Research programme: Parkinson's disease therapies - Neose/Neuronyx – undefined mechanism of action [306] Research programme: Parkinson's disease therapies - Proteome Systems (EUK-418) – free radical scavenger and oxygen radical scavenger [307] Research programme: Parkinson's disease therapeutics - TauRx Therapeutics (G2 PD; TRx 018) – synuclein inhibitor [308] Research programme: protein aggregation inhibitors - Proclara Biosciences (NPT-001; NPT-002) – various actions [309] Riluzole (PK-26124; Rilutek; RP-54274) – various actions [310] Ropinirole implant – dopamine D2, D3, and D4 receptor agonist [311] Sarsasapogenin (Cogane; JNX-1001; PYM-50028; Smilagenin) – various actions [312] Sipagladenant (KW-6356) – adenosine A2A receptor antagonist [313] SPD-474 – undefined mechanism of action [314] Sumanirole (PNU-95666; U-95666) – dopamine D2 receptor agonist [315] TAK-065 – undefined mechanism of action [316] TAK-071 – muscarinic acetylcholine M1 receptor positive allosteric modulator [317] Tc 99m TRODAT-1 – single-photon emission-computed tomography (SPECT) enhancer – diagnosis [318] Terguride (Dironyl; Mysalfon; SH-406; Teluron; transdihydrolisuride; VUFB-6638; ZK-31224) – dopamine D2 receptor agonist and other actions [319] Tozadenant (A2a-(3); RO4494351; SYN-115) – adenosine A2A receptor antagonist [320] Utreloxastat (EPI-857; PTC-857) – 15-lipoxygenase (15-LOX/ALOX15) inhibitor [321] Vipadenant (BG-14; BIIB-014; BIIB14; CEB-4520; V-2006; VER-11135; VER-A00-11; VER-A00049; VER-ADO-49; VR-2006) – adenosine A2A receptor antagonist [322] [323]
Sources: en.wikipedia.org
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.
Lowering pressure reduces the boiling point of water and allows ice to sublimate at temperatures below freezing. Vacuum also limits convective heat transfer, so heat is usually supplied by shelves or radiation. The pressure must stay below the vapor pressure of ice at the product temperature.
The cycle typically includes freezing, primary drying, and secondary drying. Freezing solidifies water and sets the pore structure; primary drying removes bulk ice; secondary drying removes bound water. Some cycles add annealing or pre-freezing steps.
Karl Fischer titration is a common method, using coulometric or volumetric detection. Thermogravimetric analysis can also measure weight loss on heating. Results depend on sample handling because the dried solid can absorb moisture quickly.