Sublimation comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Updated 2025-09-10. Numbers and descriptions here follow the published literature rather than marketing material.
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.
Lyophilized products are typically hygroscopic and require protection from moisture during storage. Manufacturers seal them in glass vials, often under vacuum or an inert gas such as nitrogen. The container closure system, including the stopper and crimp seal, must prevent water vapor ingress. Storage temperature varies from controlled room temperature to refrigerated or frozen conditions, depending on the formulation. Humidity-controlled environments are essential because even brief exposure to ambient air can degrade the product.
Stability of a lyophilized product depends on its glass transition temperature, the temperature at which the amorphous cake transitions from a glassy to a rubbery state. Storage below this temperature minimizes molecular mobility and slows chemical degradation. If the storage temperature exceeds the glass transition temperature, the cake may collapse, shrink, or become sticky. Accelerated stability studies at elevated temperatures and humidity help predict shelf life, but they do not always reflect real-time behavior. Residual moisture content also plays a critical role in long-term stability.
Reconstitution involves adding a suitable diluent, often sterile water or a buffer, to the dried cake. Gentle swirling or inversion helps dissolve the material without creating excessive foam. The time required for complete dissolution can range from seconds to several minutes and depends on the cake structure and the diluent. Improper reconstitution, such as vigorous shaking or using the wrong diluent, can cause protein aggregation or loss of activity. After reconstitution, the product may have a limited shelf life and should be used according to its labeling.
| Property | Value | Notes |
|---|---|---|
| Common name | Freeze-drying | Process removes water by sublimation under vacuum. |
| Typical primary drying shelf temperature | -40 C to -10 C | Set below the formulation's collapse temperature. |
| Typical chamber pressure | 0.05-0.3 mbar | Low pressure allows ice to sublime below its triple point. |
| Water content after drying | 0.5-3% by weight | Higher values may reduce storage stability for some materials. |
| Key thermal parameter | Collapse temperature | Measured by freeze-drying microscopy or differential scanning calorimetry. |
Lyophilization removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts liquid water into ice and fixes the structure of the sample. After freezing, primary drying lowers pressure so ice changes directly to vapor without passing through a liquid phase. Secondary drying then removes bound water that remains after ice sublimation. The result is a dry, porous solid that often retains its original shape.
The low pressure used during drying allows water vapor to move from the ice surface to a cold condenser. Energy supplied as heat drives sublimation but must stay below the collapse temperature of the frozen matrix. If the product becomes too warm, the frozen structure may soften or melt, reducing pore formation and slowing drying. Formulations often include bulking agents, stabilizers, or buffers to support a rigid cake. The final moisture content depends on formulation, freezing rate, and the length of secondary drying.
Freeze-drying is distinct from simple evaporation and from spray drying. Evaporation removes water at temperatures above freezing, while spray drying rapidly dries droplets in a heated gas stream. Lyophilization avoids high temperatures, which can be useful for heat-sensitive materials such as proteins, vaccines, and some foods. The porous cake produced by sublimation dissolves or rehydrates more quickly than a dense dried mass. Not all materials tolerate freezing or the pH shifts that can occur as solutes concentrate during ice formation.
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.
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.
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.
15. Biofizika. 2014 Sep-Oct;59(5):1023-6. [Main mechanisms of rhabdomyolysis-caused kidney injury and their correction by organospecific peptides]. [Article in Russian] Zamorskiĭ II, Shchudrova TS. The influence of the organospecific peptides--kidney tripeptides T-31 and T-35, pineal tetrapeptide epitalon on the main mechanisms of kidney injury caused by experimental rhabdomyolysis--toxic injury of tubular cells, development of oxidative stress and energetic misbalance, leading to significant disturbances of the functional state of kidneys and development of acute kidney failure was studied. The renoprotective effect of oligopeptides realized by impact on all of the indicated mechanisms of kidney injury and confirmed by correlation between them was estimated.
73. Bromocriptine. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2026 Sep 15. Bromocriptine is usually not used during breastfeeding because it suppresses lactation. The indication of lactation suppression has been withdrawn in the U.S. and discouraged in other countries because it increases the risk of maternal stroke, seizures, cardiovascular disorders, death and possibly psychosis.[1-4] A low dose of 2.5 mg once daily has been used for 3 days to decrease overproduction of milk.[5] The drug was undetectable in milk with this dosage and infants had no adverse reactions, but the safety of this use is not clearly established. Postpartum women may clear bromocriptine more rapidly than others.[6] Case reports and series also exist of mothers treated with bromocriptine for amenorrhea-galactorrhea syndrome or prolactinoma during pregnancy and lactation who successfully breastfed their infants. Bromocriptine has been used to treat persistent galactorrhea following breast augmentation surgery.[7] It has also been used to mitigate hyperprolactinemia and galactorrhea caused by antipsychotic therapy.[8]
8 October – Tánaiste Micheál Martin said that the Department of Foreign Affairs had been in touch with the family of Kim Damti (22), an Irish-Israeli woman who was unaccounted for following the previous day's series of attacks launched by Hamas on Israel. On 11 October, Damti was confirmed dead. 10 October – Minister for Finance Michael McGrath and Minister for Public Expenditure, National Development Plan Delivery and Reform Paschal Donohoe announced Budget 2024, with three electricity credits for all households, a €12 increase to core social welfare payments and half-price travel for those aged under 25. 23 October – Yousef Palani was sentenced to two life sentences plus 20 years for the murder of two men and the stabbing of a third in Sligo, all of who he had sought out on a pretence of dating. 25 October – The Health Products Regulatory Authority (HPRA) said it had seized 254 units of falsified Semaglutide, a drug used for type 2 diabetes and as an unofficial aide to weight loss, during 2023. 27 October – Latest figures showed that homelessness in Ireland hit new records: 8,923 adults and 3,904 children accessed emergency accommodation in September 2023, bringing the total to 12,827 people.
Sources: pubmed.ncbi.nlm.nih.gov
The laser produces light of a selected wavelength. The beam of light hits the analyte in the spots of the microarrays and refracts. The mass of the analyte causes the angle of reflected light to be different from the angle of incident light. The reflective properties of the CD/DVD change based on the quantity of analyte in the sample. The attenuated signal reaches the photodiode of the drive's pickup. Analog signals are extracted, digitized, and converted to an image. The signal or optical density of the image is inversely proportional to concentration. The refractive index of light, which is directly proportional to concentration, can also be measured. A readable signal is only generated if the sample is at least 200 nm, otherwise it is too small to significantly disrupt reflection of incident laser light. DVD diagnostic software programs such as Kprobe, ODC, and PlexUtilities can also be used for testing arrays and assays prepared on DVDs. These programs rely on a basic DVD error correcting algorithm. DVDs are organized by sectors which each consist of 2064 bytes. A logical error correction code (ECC) block consists of 16 data sectors. The ECC block is the basic unit for testing disk quality by counting the number of parity inner errors (PIE) or parity inner failures (PIF). The software programs can analyze PIF density which is proportional to analyte concentration.
Gingras has published > 200 articles that have been cited > 35,000 times (Google Scholar; Feb 2020). In 2011, Gingras was named one of Canada's Top 100 Most Powerful Women. In 2015, Gingras was elected a fellow of the Royal Society of Canada. Her work on interaction proteomics, was awarded, alongside John Yates, the Discovery Award in Proteomics from the Human Proteome Organization (2019). She also received the Jeanne Manery Fisher Memorial Lecture award at the 2019 meeting of the Canadian Society for Molecular Biosciences.
BioLegend is a global developer and manufacturer of antibodies and reagents used in biomedical research located in San Diego, California. It was incorporated in June 2002 and has since expanded to include BioLegend Japan KK, where it is partnered with Tomy Digital Biology Co., Ltd. in Tokyo, BioLegend Europe in the United Kingdom, BioLegend GmbH in Germany, and BioLegend UK Ltd in the United Kingdom. In July 2021, BioLegend was acquired by PerkinElmer for $5.25 billion and now operates as Revvity. BioLegend manufactures products in the areas of neuroscience, cell immunophenotyping, cytokines and chemokines, adhesion, cancer research, T regulatory cells, stem cells, innate immunity, cell-cycle analysis, apoptosis, and modification-specific antibodies. Reagents are created for use in flow cytometry, proteogenomics, ELISA, immunoprecipitation, Western blotting, immunofluorescence microscopy, immunohistochemistry, and in vitro or in vivo functional assays.
Sources: en.wikipedia.org
In March 2003, Cambridge Antibody Technology (CAT) stated its wish to "initiate discussions regarding the applicability of the royalty offset provisions for Humira" with Abbott Laboratories in the High Court of London. In November 2004, the trial began, and in December 2004, Justice Hugh Laddie ruled for CAT. A short version of the full statement of the proceedings was released. In it Justice Laddie remarked, "Abbott was in error when it made its first royalty payment to CAT calculated on the basis that only 2% of the Net Sales was due. It should have calculated on the basis of the full royalty of just over 5% and should have paid and continued to pay CAT accordingly." Justice Laddie went on to observe "...that the construction advanced by Abbott does violence to the language of the agreements, renders them obscure and makes little or no commercial sense. For this reason CAT wins the action." Abbott was required to pay CAT US$255 million, some of which was to be passed to its partners in development. Of this sum, the Medical Research Council received US$191 million, and in addition, Abbott was asked to pay the MRC a further US$7.5 million over five years from 2006, providing that Humira remains on the market. The MRC also is to receive a further £5.1 million (sterling) in respect of past royalties.
Network Science, Part 5: Solvent-Accessible Surfaces AREAIMOL is a command line tool in the CCP4 Program Suite for calculating ASA. NACCESS solvent accessible area calculations. FreeSASA Open source command line tool, C library and Python module for calculating ASA. Surface Racer Oleg Tsodikov's Surface Racer program. Solvent accessible and molecular surface area and average curvature calculation. Free for academic use. ASA.py — a Python-based implementation of the Shrake-Rupley algorithm. Michel Sanner's Molecular Surface – the fastest program to calculate the excluded surface. pov4grasp render molecular surfaces. Molecular Surface Package — Michael Connolly's program. Volume Voxelator — A web-based tool to generate excluded surfaces. ASV freeware Analytical calculation of the volume and surface of the union of n spheres (Monte-Carlo calculation also provided). Vorlume Computing Surface Area and Volume of a Family of 3D Balls. GetArea Calculate solvent accessible surface area of proteins online. ProMS ProMS - Protein Molecular Surface Calculator
ProIAPP consists of 67 amino acids, which follow a 22 amino acid signal peptide which is rapidly cleaved after translation of the 89 amino acid coding sequence. The human sequence (from N-terminus to C-terminus) is: (MGILKLQVFLIVLSVALNHLKA) TPIESHQVEKR^ KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTYG^ KR^ NAVEVLKREPLNYLPL. The signal peptide is removed during translation of the protein and transport into the endoplasmic reticulum. Once inside the endoplasmic reticulum, a disulfide bond is formed between cysteine residues numbers 2 and 7. Later in the secretory pathway, the precursor undergoes additional proteolysis and posttranslational modification (indicated by ^). 11 amino acids are removed from the N-terminus by the enzyme proprotein convertase 2 (PC2) while 16 are removed from the C-terminus of the proIAPP molecule by proprotein convertase 1/3 (PC1/3). At the C-terminus Carboxypeptidase E then removes the terminal lysine and arginine residues. The terminal glycine amino acid that results from this cleavage allows the enzyme peptidylglycine alpha-amidating monooxygenase (PAM) to convert the terminal glycine to an amine group (releasing glycolate). After this step, the transformation from the precursor protein proIAPP to the biologically active IAPP (amylin) is complete (IAPP sequence: KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2).
Sources: en.wikipedia.org
Primary drying removes ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, often under the same vacuum. The two stages differ in the water state being removed.
Freezing determines ice crystal size, pore structure, and the concentration of solutes in remaining liquid. Faster freezing generally creates smaller ice crystals and a denser dried matrix. These features affect drying rate and reconstitution behavior.
Lyophilization reduces water content but usually leaves a small amount of water in the dried material. Some water remains bound to solids or trapped in the dried matrix. Very low water targets can require extended secondary drying, which may alter product stability.
Lyophilized products should be stored in airtight containers, protected from moisture and light, at the temperature specified by the manufacturer. Many require refrigeration at 2–8 °C, while some need frozen storage. Always check the product label for specific conditions.