A practical reference on Primary drying: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.
Reviewed 2026-05-10. Anything still debated is marked as such rather than presented as settled.
Industries use lyophilization for pharmaceuticals, biological products, and food preservation. In the pharmaceutical sector, it extends the shelf life of injectable drugs, vaccines, and proteins that are unstable in aqueous solution. Food manufacturers apply freeze-drying to coffee, fruits, and ready meals to retain flavor and texture. The process is energy-intensive and requires specialized equipment, which limits its use to high-value products. Ongoing research examines how formulation and process parameters affect the quality of the final dried product.
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.
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.
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.
| 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. |
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.
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.
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.
A formulation often contains excipients that protect the active ingredient during freezing and drying. Bulking agents provide structure, while lyoprotectants stabilize sensitive molecules. The freezing step can produce ice crystals whose size and distribution affect the drying rate, and cycle design includes freezing, annealing, and drying phases. If the product temperature rises above a critical value, the cake may collapse or lose its porous structure. Successful lyophilization therefore depends on the interaction between formulation, equipment, and cycle design.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen to convert liquid water into ice. Next, the pressure is reduced below the triple point of water so that ice changes directly into vapor without passing through a liquid phase. This step is called primary drying. The result is a porous solid or cake that retains the original shape of the frozen solution.
After primary drying, secondary drying removes water that remains bound to the material. This stage raises the shelf temperature while maintaining low pressure, which encourages desorption of unfrozen water. Residual moisture can be reduced to a low percentage, improving stability for many products. The process parameters, including freezing rate, shelf temperature, and chamber pressure, influence the final pore structure and reconstitution behavior. Control of these variables helps prevent collapse or meltback during drying.
Irvine stated that he "criticized Freud and other theorists for projecting male constructs of sexuality onto women" and "viewed the clitoris as the main center of sexual response". He considered the vagina to be "relatively unimportant" for sexual satisfaction, relaying that "few women inserted fingers or objects into their vaginas when they masturbated". Believing that vaginal orgasms are "a physiological impossibility" because the vagina has insufficient nerve endings for sexual pleasure or climax, he "concluded that satisfaction from penile penetration [is] mainly psychological or perhaps the result of referred sensation". Masters and Johnson's research, as well as Shere Hite's, generally supported Kinsey's findings about the female orgasm. Masters and Johnson were the first researchers to determine that the clitoral structures surround and extend along and within the labia. They observed that both clitoral and vaginal orgasms have the same stages of physical response, and found that the majority of their subjects could only achieve clitoral orgasms, while a minority achieved vaginal orgasms. On that basis, they argued that clitoral stimulation is the source of both kinds of orgasms, reasoning that the clitoris is stimulated during penetration by friction against its hood. The research came at the time of the second-wave feminist movement, which inspired feminists to reject the distinction made between clitoral and vaginal orgasms.
where the ion AB+ collides with the neutral species M and subsequently breaks apart. The details of this process are described by collision theory. Due to different instrumental configuration, two main different types of CID are possible: (i) beam-type (in which precursor ions are fragmented on-the-flight) and (ii) ion trap-type (in which precursor ions are first trapped, and then fragmented). A third and more recent type of CID fragmentation is higher-energy collisional dissociation (HCD). HCD is a CID technique specific to orbitrap mass spectrometers in which fragmentation takes place external to the ion trap, it happens in the HCD cell (in some instruments named "ion routing multipole"). HCD is a trap-type fragmentation that has been shown to have beam-type characteristics. Freely available large scale high resolution tandem mass spectrometry databases exist (e.g. METLIN with 960,000 molecular standards each with experimental CID MS/MS data), and are typically used to facilitate small molecule identification.
== Participants == The negotiations involved senior political, diplomatic, and security officials from both countries. The United States delegation of nearly 300 members was led by Vice President JD Vance and included senior officials such as special envoy Steve Witkoff and presidential adviser Jared Kushner. According to a senior official cited by BBC News, the broader delegation also included National Security Adviser Andrew Baker and Asian affairs adviser Michael Vance. Additional subject-matter experts were present in Islamabad, with further support teams based in Washington, D.C. The Iranian delegation consisted of around 70 members, led by parliamentary speaker Mohammad Bagher Ghalibaf and Foreign Minister Abbas Araghchi, along with additional political, security, and economic officials. The reported members included:
=== Partnerships === In 2012, Safeway invested $350 million into retrofitting 800 locations with clinics that would offer in-store blood tests. After many missed deadlines and questionable results from a trial clinic at Safeway's corporate offices, the deal was terminated in 2015. In 2013, Theranos partnered with Walgreens to offer in-store blood tests at more than 40 locations. Although Theranos blood tests were reportedly used on drug trial patients for GlaxoSmithKline and Pfizer, both companies stated in October 2015 that there were no active projects with Theranos. In June 2016, Walgreens terminated its partnership with Theranos. In November 2016, it filed a suit against Theranos in federal court in Delaware for breach of contract. In June 2017, Theranos reported to investors that the suit, which originally sought $140 million in damages, was settled for less than $30 million. In March 2015, the Cleveland Clinic announced a partnership with Theranos to test its technology and decrease the cost of lab tests. In July 2015, Theranos became the lab-work provider for Pennsylvania insurers AmeriHealth Caritas and Capital Blue Cross. The same month, the Food and Drug Administration approved the use of the company's fingerstick blood testing device for the herpes simplex virus (HSV-1) outside a clinical laboratory setting. Theranos was named the 2015 Bioscience Company of the Year by the Arizona BioIndustry Association (AzBio).
Sources: en.wikipedia.org
=== Veterinary use === An SSRI (fluoxetine) has been approved for veterinary use in treatment of canine separation anxiety. Like in human medicine, fluoxetine is extensively used off-label in animal medicine. In dogs and cats, it is mainly prescribed off-label for behavior problems.
The US Food and Drug Administration granted the application for datopotamab deruxtecan priority review and breakthrough therapy designations. Efficacy was evaluated in TROPION-Breast02 (NCT05374512), a multicenter, open-label, randomized trial of 644 participants with unresectable or metastatic triple-negative breast cancer who had not received prior chemotherapy or other systemic anti-cancer therapy for unresectable or metastatic breast cancer and who were not candidates for PD-1/PD-L1 inhibitor therapy. Participants were excluded for a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening. Randomization was stratified by geographical region (United States, Canada and Europe, or rest of world), PD-L1 status (positive or negative) and disease-free interval history (de novo or ≤12 months or >12 months). Participants were randomized (1:1) to receive either datopotamab deruxtecan-dlnk (N=323) or investigator's choice of chemotherapy (N=321); paclitaxel (28%), nab-paclitaxel (54%), capecitabine (2.2%), eribulin (11%) or carboplatin (4.7%).
The prefect of Puno, Benito Laso de la Vega, tried to convince his colleagues in Lampa, Agustín Gamarra from Cuzco and Antonio Gutiérrez de la Fuente from Arequipa, of a project of "microfederalism" or "provincial federation" to separate the south and force the whole country to join the Andean federation of Bolívar. Santa Cruz did everything he could to prevent greater autonomy in the regions and persecute any separatist movement. He removed Laso from his duties and warned the other two. Later, during the Gran Colombian-Peruvian War, Sucre's anti-Peruvian attitudes were denounced, who, to commemorate the triumph of the Gran Columbian army over the Peruvian advance, ordered the construction of a commemorative obelisk on the site where the battle occurred, with an inscription increasing the number of Peruvian soldiers that took part in action and decreasing their own, in the following terms: "The Peruvian army of 8,000 soldiers that invaded the land of their liberators, was defeated by 4,000 braves from Colombia on February 27, 1829." José de la Mar protested the words on the monument, which he considered triumphalist and erroneous. In addition, he complained about the treatment received by the Peruvian dead and prisoners after the battle, with emphasis on the decapitation of the corpse of Pedro Raulet, one of the officers who fell in Tarqui, whose head was nailed to a pike and paraded through the streets of Cuenca.
=== Biogas production === The biogas produced from feces when it is contained in sewage and treated in an anaerobic digestion process could be worth as much as US$9.5 billion. Washington DC plans to produce biogas from sewage sludge, the by-product of sewage treatment, which will save US$13 million a year. Teams from the Cambridge Development Initiative, led by Stanford researcher Maisam Pyarali, began a project in 2015 to convert sewage from the slums of Dar Es Salaam into biogas and fertilizer with solar concentrators.
=== Side effects === Nicomorphine's side effects are similar to those of other opioids and include itching, nausea and respiratory depression. It is considered by doctors to be one of the better analgesics for the comprehensive mitigation of suffering, as opposed to purely clouding the noxious pain stimulus, in the alleviation of chronic pain conditions.
Sources: en.wikipedia.org
Vaccines must be handled and transported according to international regulations, be maintained at controlled temperatures that vary across vaccine technologies, and be used for immunization before deterioration in storage. The scale of the COVID‑19 vaccine supply chain is expected to be vast to ensure delivery worldwide to vulnerable populations. Priorities for preparing facilities for such distribution include temperature-controlled facilities and equipment, optimizing infrastructure, training immunization staff, and rigorous monitoring. RFID technologies are being implemented to track and authenticate a vaccine dose from the manufacturer along the entire supply chain to the vaccination. In September 2020, Grand River Aseptic Manufacturing agreed with Johnson & Johnson to support the manufacture of its vaccine candidate, including technology transfer and fill and finish manufacturing. In October 2020, it was announced that the Moderna vaccine candidate will be manufactured in Visp, Switzerland by its partner Lonza Group, which plans to produce the first doses in December 2020. The newly built 2,000-square-metre facility will ramp up production to 300 million doses annually. The ingredient will be shipped frozen at −70 °C to Spain's Laboratorios Farmacéuticos Rovi SA for the final stage of manufacturing. Lonza's site in Portsmouth, New Hampshire, aimed to start making vaccine ingredients exclusively for the U.S. by November 2020.
=== TikTok === TikTok has especially become a social media platform where mental health and illnesses are talked about more freely. The National institutes of Health (NIH) released in 2015 that more than 1/3 of Americans use the internet to help "diagnose their ailments", including mental illnesses. TikTok videos promoting either self-diagnosis or possible symptoms of different illnesses has caused an increase of internet users to believe they have a disorder, when in reality they may or may not. Additionally, TikTok keeps up with the latest trends, and some trends touch upon mental health (positively or negatively, depending on the point of view). One trend, as explained by the Philadelphia Magazine, uses intermittent fasting to heal anxiety. However, some individuals, including licensed counselors such as Akua K. Boateng argue that this advice is actually very detrimental in actually promoting bad mental habits instead, including the possible development of eating disorders. Other trends, including "What I eat in a day" Tiktoks, have been also labeled as harmful by health professionals, since these videos may lead viewers to habits of unhealthy comparison and goals of developing the "societal accepted body". With a majority of these videos reaching women especially, many believe that viewers may become more vulnerable, leading to unhealthy eating habits.
== Notable acid-fast structures == Very few structures are acid-fast; this makes staining for acid-fastness particularly useful in diagnosis. The following are notable examples of structures which are acid-fast or modified acid-fast:
=== N05BA Benzodiazepine derivatives === N05BA01 Diazepam N05BA02 Chlordiazepoxide N05BA03 Medazepam N05BA04 Oxazepam N05BA05 Dipotassium clorazepate N05BA06 Lorazepam N05BA07 Adinazolam N05BA08 Bromazepam N05BA09 Clobazam N05BA10 Ketazolam N05BA11 Prazepam N05BA12 Alprazolam N05BA13 Halazepam N05BA14 Pinazepam N05BA15 Camazepam N05BA16 Nordazepam N05BA17 Fludiazepam N05BA18 Ethyl loflazepate N05BA19 Etizolam N05BA21 Clotiazepam N05BA22 Cloxazolam N05BA23 Tofisopam N05BA24 Bentazepam N05BA25 Mexazolam N05BA26 Oxazolam N05BA27 Metaclazepam N05BA56 Lorazepam, combinations
The new refrigerating technology first met with widespread industrial use as a means to freeze meat supplies for transport by sea in reefer ships from the British Dominions and other countries to the British Isles. Although not actually the first to achieve successful transportation of frozen goods overseas (the Strathleven had arrived at the London docks on 2 February 1880 with a cargo of frozen beef, mutton and butter from Sydney and Melbourne), the breakthrough is often attributed to William Soltau Davidson, an entrepreneur who had emigrated to New Zealand. Davidson thought that Britain's rising population and meat demand could mitigate the slump in world wool markets that was heavily affecting New Zealand. After extensive research, he commissioned the Dunedin to be refitted with a compression refrigeration unit for meat shipment in 1881. On February 15, 1882, the Dunedin sailed for London with what was to be the first commercially successful refrigerated shipping voyage, and the foundation of the refrigerated meat industry. The Times commented "Today we have to record such a triumph over physical difficulties, as would have been incredible, even unimaginable, a very few days ago ...". The Marlborough — sister ship to the Dunedin — was immediately converted and joined the trade the following year, along with the rival New Zealand Shipping Company vessel Mataurua, while the German Steamer Marsala began carrying frozen New Zealand lamb in December 1882.
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.
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.