In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are: Hard-shelled capsules, which contain dry, powdered ingredients or miniature pellets made by e.g. processes of extrusion or spheronization. These are made in two halves: a smaller-diameter “body”, filled and sealed using a larger-diameter “cap”. Soft-shelled capsules used for oils and for active ingredients that are dissolved or suspended in oil. Both of these classes of capsules are made from aqueous solutions of gelling agents, such as animal protein or plant polysaccharides or their derivatives. Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or sorbitol to decrease the capsule's hardness, coloring agents, disintegrants and surface treatment. Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication.
For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the “caplet”, a portmanteau of “capsule-shaped tablet”, in order to tie this positive association to more efficiently-produced tablet pills, as well as being an easier-to-swallow shape than the usual disk-shaped tablet. In 1833, Mothes and Dublanc were granted a patent for a method to produce a single-piece gelatin capsule, sealed with a drop of gelatin solution, they used individual iron molds for their process, filling the capsules individually with a medicine dropper. On, methods were developed that used sets of plates with pockets to form the capsules. Although some companies still use this method, the equipment is no longer produced commercially. All modern soft-gel encapsulation uses variations of a process developed by R. P. Scherer in 1933, his innovation used. They were filled by blow molding; this method was high-yield and reduced waste. Softgels can be an effective delivery system for oral drugs poorly soluble drugs.
This is because the fill can contain liquid ingredients that help increase solubility or permeability of the drug across the membranes in the body. Liquid ingredients are difficult to include in any other solid dosage form such as a tablet. Softgels are highly suited to potent drugs, where the reproducible filling process helps ensure each softgel has the same drug content, because the operators are not exposed to any drug dust during the manufacturing process. In 1949, the Lederle Laboratories division of the American Cyanamid Company developed the "Accogel" process, allowing powders to be filled into soft gelatin capsules. James Murdock of London patented the two-piece telescoping gelatin capsule in 1847; the capsules are made in two parts by dipping metal pins in the gelling agent solution. The capsules are supplied as closed units to the pharmaceutical manufacturer. Before use, the two halves are separated, the capsule is filled with powder or more pellets made by the process of Extrusion & Spheronization and the other half of the capsule is pressed on.
With the compressed slug method, weight varies less between capsules. However, the machinery required to manufacture them is more complex; the powder or spheroids inside the capsule contains the active ingredient and any excipients, such as binders, fillers and preservatives. Gelatin capsules, informally called gel caps or gelcaps, are composed of gelatin manufactured from the collagen of animal skin or bone. Vegetable capsules are composed of a polymer formulated from cellulose. Or Pullulan, polysaccharide polymer produced from tapioca starch; the process of encapsulation of hard gelatin capsules can be done on manual, semi-automatic and automatic capsule filling machines. Softgels are filled at the same time as they are produced and sealed on the rotary die of a automatic machine. Capsule fill weight is a critical attribute in encapsulation and various real time fill weight monitoring techniques such as near-infrared spectroscopy and vibrational spectroscopy are used, as well as in-line weight checks, to ensure product quality.
Capsule endoscopy OROS Pharmacy Automation - The Tablet Counter Pharmaceutical formulation Pill splitting Tablet Oblaat L. Lachman. A. Lieberman. L. Kanig; the Theory and Practice of Industrial Pharmacy. Lea & Febiger, Philadelphia. ISBN 0-8121-0977-5
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion, they are used in food, drug delivery, chemical industries, as well as agriculture and environmental engineering. Cyclodextrins are composed of 5 or more α-D-glucopyranoside units linked 1->4, as in amylose. The largest cyclodextrin contains 32 1,4-anhydroglucopyranoside units, while as a poorly characterized mixture, at least 150-membered cyclic oligosaccharides are known. Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape: α -cyclodextrin: 6 glucose subunits β -cyclodextrin: 7 glucose subunits γ -cyclodextrin: 8 glucose subunits With an hydrophobic interior and hydrophilic exterior, cyclodextrins form complexes with hydrophobic compounds. Alpha-, beta-, gamma-cyclodextrin are all recognized as safe by the U. S. FDA, they have been applied for delivery of a variety of drugs, including hydrocortisone, nitroglycerin, chloramphenicol.
The cyclodextrin confers stability to these drugs. The inclusion compounds of cyclodextrins with hydrophobic molecules are able to penetrate body tissues, these can be used to release biologically active compounds under specific conditions. In most cases the mechanism of controlled degradation of such complexes is based on pH change of water solutions, leading to the loss of hydrogen or ionic bonds between the host and the guest molecules. Alternative means for the disruption of the complexes take advantage of heating or action of enzymes able to cleave α-1,4 linkages between glucose monomers. Cyclodextrins were shown to enhance mucosal penetration of drugs. Β-cyclodextrins are used to produce stationary phase media for HPLC separations. Cyclodextrins bind fragrances; such devices are capable of releasing fragrances during ironing or when heated by human body. They are the main ingredient in Febreze which claims that the β-cyclodextrins "trap" odor causing compounds, thereby reducing the odor.
Such a device used is a typical'dryer sheet'. The heat from a clothes dryer releases the fragrance into the clothing. Cyclodextrins are used to produce alcohol powder by encapsulating ethanol; the powder produces an alcoholic beverage when mixed with water. Typical cyclodextrins are constituted by 6-8 glucopyranoside units; these subunits are linked by 1,4 glycosidic bonds. The cyclodextrins have toroidal shapes, with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively; because of this arrangement, the interior of the toroids is not hydrophobic, but less hydrophilic than the aqueous environment and thus able to host other hydrophobic molecules. In contrast, the exterior is sufficiently hydrophilic to impart cyclodextrins water solubility, they are not soluble in typical organic solvents. Cyclodextrins are prepared by enzymatic treatment of starch. Cyclodextrin glycosyltransferase is employed along with α-amylase. First starch is liquified either by heat treatment or using α-amylase CGTase is added for the enzymatic conversion.
CGTases produce mixtures of cyclodextrins, thus the product of the conversion results in a mixture of the three main types of cyclic molecules, in ratios that are dependent on the enzyme used: each CGTase has its own characteristic α:β:γ synthesis ratio. Purification of the three types of cyclodextrins takes advantage of the different water solubility of the molecules: β-CD, poorly water-soluble can be retrieved through crystallization while the more soluble α- and γ-CDs are purified by means of expensive and time consuming chromatography techniques; as an alternative a "complexing agent" can be added during the enzymatic conversion step: such agents form a complex with the desired cyclodextrin which subsequently precipitates. The complex formation drives the conversion of starch towards the synthesis of the precipitated cyclodextrin, thus enriching its content in the final mixture of products. Wacker Chemie AG uses dedicated enzymes, that can produce alpha-, beta- or gamma-cyclodextrin specifically.
This is valuable for the food industry, as only alpha- and gamma-cyclodextrin can be consumed without a daily intake limit. Interest in cyclodextrins is enhanced because their host–guest behavior can be manipulated by chemical modification of the hydroxyl groups. O-Methylation and acetylation are typical conversions. Propylene oxide gives hydroxypropylated derivatives; the primary alcohols can be tosylated. The degree of derivatization is an i.e. full methylation vs partial. Both β-cyclodextrin and methyl-β-cyclodextrin remove cholesterol from cultured cells; the methylated form MβCD was found to be more efficient than β-cyclodextrin. The water-soluble MβCD is known to form soluble inclusion complexes with cholesterol, thereby enhancing its solubility in aqueous solution. MβCD is employed for the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is lodged inside cyclodextrin rings. MβCD is employed in research to disrupt lipid rafts by removing cholesterol from membranes.
In supramolecular chemistry, cyclodextrins are precursors to mechanically interlocked molecular architectures, such as rotaxanes and catenanes. Illustrative, α-cyclodextrin form second-sphere coordination complex with tetrabromoaurate anion. Beta-cyclodextrin complexes with certain c
A powder is a dry, bulk solid composed of a large number of fine particles that may flow when shaken or tilted. Powders are a special sub-class of granular materials, although the terms powder and granular are sometimes used to distinguish separate classes of material. In particular, powders refer to those granular materials that have the finer grain sizes, that therefore have a greater tendency to form clumps when flowing. Granulars refers to the coarser granular materials. Many manufactured goods come in powder form, such as flour, ground coffee, powdered milk, copy machine toner, cosmetic powders, some pharmaceuticals. In nature, fine sand and snow, volcanic ash, the top layer of the lunar regolith are examples; because of their importance to industry and earth science, powders have been studied in great detail by chemical engineers, mechanical engineers, physicists and researchers in other disciplines. A powder can be compacted or loosened into a vastly larger range of bulk densities than can a coarser granular material.
When deposited by sprinkling, a powder may be light and fluffy. When vibrated or compressed it may become dense and lose its ability to flow; the bulk density of coarse sand, on the other hand, does not vary over an appreciable range. The clumping behavior of a powder arises because of the molecular Van der Waals force that causes individual grains to cling to one another; this force is present not just in sand and gravel, too. However, in such coarse granular materials the weight and the inertia of the individual grains are much larger than the weak Van der Waals forces, therefore the tiny clinging between grains does not have a dominant effect on the bulk behavior of the material. Only when the grains are small and lightweight does the Van der Waals force become predominant, causing the material to clump like a powder; the cross-over size between flow conditions and stick conditions can be determined by simple experimentation. Many other powder behaviors are common to all granular materials.
These include segregation, stratification and unjamming, loss of kinetic energy, frictional shearing and Reynolds' dilatancy. Powders are transported in the atmosphere differently from a coarse granular material. For one thing, tiny particles have little inertia compared to the drag force of the gas that surrounds them, so they tend to go with the flow instead of traveling in straight lines. For this reason, powders may be an inhalation hazard. Larger particles cannot weave through the body's defenses in the nose and sinus, but will strike and stick to the mucous membranes; the body moves the mucous out of the body to expel the particles. The smaller particles on the other hand can travel all the way to the lungs from which they cannot be expelled. Serious and sometimes fatal diseases such as silicosis are a result from working with certain powders without adequate respiratory protection. If powder particles are sufficiently small, they may become suspended in the atmosphere for a long time. Random motion of the air molecules and turbulence provide upward forces that may counteract the downward force of gravity.
Coarse granulars, on the other hand, are so heavy that they fall back to the ground. Once disturbed, dust may form huge dust storms that cross continents and oceans before settling back to the surface; this explains why there is little hazardous dust in the natural environment. Once aloft, the dust is likely to stay aloft until it meets water in the form of rain or a body of water, it sticks and is washed downstream to settle as mud deposits in a quiet lake or sea. When geological changes re-expose these deposits to the atmosphere, they may have cemented together to become mudstone, a type of rock. For comparison, the Moon has neither wind nor water, so its regolith contains dust but no mudstone; the cohesive forces between the particles tend to resist their becoming airborne, the motion of wind across the surface is less to disturb a low-lying dust particle than a larger sand grain that protrudes higher into the wind. Mechanical agitation such as vehicle traffic, digging or passing herds of animals is more effective than a steady wind at stirring up a powder.
The aerodynamic properties of powders are used to transport them in industrial applications. Pneumatic conveying is the transport of grains through a pipe by blowing gas. A gas fluidized bed is a container filled with a powder or granular substance, fluffed up by blowing gas upwardly through it; this is used for fluidized bed combustion, chemically reacting the gas with the powder.' Some powders may be dustier than others. The tendency of a powder to generate particles in the air under a given energy input is called "dustiness", it is an important powder property, relevant to powder aerosolization process. It has indications for human exposure to aerosolized particles and associated health risks at workplaces. Various dustiness testing methods have been established in research laboratories, in order to predict powder behaviors during aerosolization; these methods allow application of a wide range of energy inputs to powdered materials, which simulates different real-life scenarios. Many common powders made in industry are combustible.
Since powders have a high surface area, they can combust with explosive force once ignited. Facilities such as flour mills can be vulnerable to such explosions without proper dust mitigation efforts; some metals become dange
Munich is the capital and most populous city of Bavaria, the second most populous German federal state. With a population of around 1.5 million, it is the third-largest city in Germany, after Berlin and Hamburg, as well as the 12th-largest city in the European Union. The city's metropolitan region is home to 6 million people. Straddling the banks of the River Isar north of the Bavarian Alps, it is the seat of the Bavarian administrative region of Upper Bavaria, while being the most densely populated municipality in Germany. Munich is the second-largest city in the Bavarian dialect area, after the Austrian capital of Vienna; the city is a global centre of art, technology, publishing, innovation, education and tourism and enjoys a high standard and quality of living, reaching first in Germany and third worldwide according to the 2018 Mercer survey, being rated the world's most liveable city by the Monocle's Quality of Life Survey 2018. According to the Globalization and World Rankings Research Institute Munich is considered an alpha-world city, as of 2015.
Munich is a major international center of engineering, science and research, exemplified by the presence of two research universities, a multitude of scientific institutions in the city and its surroundings, world class technology and science museums like the Deutsches Museum and BMW Museum.. Munich houses many multinational companies and its economy is based on high tech, the service sector and creative industries, as well as IT, biotechnology and electronics among many others; the name of the city is derived from the Old/Middle High German term Munichen, meaning "by the monks". It derives from the monks of the Benedictine order, who ran a monastery at the place, to become the Old Town of Munich. Munich was first mentioned in 1158. Catholic Munich resisted the Reformation and was a political point of divergence during the resulting Thirty Years' War, but remained physically untouched despite an occupation by the Protestant Swedes. Once Bavaria was established as a sovereign kingdom in 1806, it became a major European centre of arts, architecture and science.
In 1918, during the German Revolution, the ruling house of Wittelsbach, which had governed Bavaria since 1180, was forced to abdicate in Munich and a short-lived socialist republic was declared. In the 1920s, Munich became home to several political factions, among them the NSDAP; the first attempt of the Nazi movement to take over the German government in 1923 with the Beer Hall Putsch was stopped by the Bavarian police in Munich with gunfire. After the Nazis' rise to power, Munich was declared their "Capital of the Movement". During World War II, Munich was bombed and more than 50% of the entire city and up to 90% of the historic centre were destroyed. After the end of postwar American occupation in 1949, there was a great increase in population and economic power during the years of Wirtschaftswunder, or "economic miracle". Unlike many other German cities which were bombed, Munich restored most of its traditional cityscape and hosted the 1972 Summer Olympics; the 1980s brought strong economic growth, high-tech industries and scientific institutions, population growth.
The city is home to major corporations like BMW, Siemens, MAN, Linde and MunichRE. Munich is home to many universities and theatres, its numerous architectural attractions, sports events and its annual Oktoberfest attract considerable tourism. Munich is one of the fastest growing cities in Germany, it is a top-ranked destination for expatriate location. Munich hosts more than 530,000 people of foreign background; the first known settlement in the area was of Benedictine monks on the Salt road. The foundation date is not considered the year 1158, the date the city was first mentioned in a document; the document was signed in Augsburg. By the Guelph Henry the Lion, Duke of Saxony and Bavaria, had built a toll bridge over the river Isar next to the monk settlement and on the salt route, but as part of the archaeological excavations at Marienhof in advance of the expansion of the S-Bahn from 2012 shards of vessels from the eleventh century were found, which prove again that the settlement Munich must be older than their first documentary mention from 1158.
In 1175 Munich received city fortification. In 1180 with the trial of Henry the Lion, Otto I Wittelsbach became Duke of Bavaria, Munich was handed to the Bishop of Freising. In 1240, Munich was transferred to Otto II Wittelsbach and in 1255, when the Duchy of Bavaria was split in two, Munich became the ducal residence of Upper Bavaria. Duke Louis IV, a native of Munich, was elected German king in 1314 and crowned as Holy Roman Emperor in 1328, he strengthened the city's position by granting it the salt monopoly, thus assuring it of additional income. In the late 15th century, Munich underwent a revival of gothic arts: the Old Town Hall was enlarged, Munich's largest gothic church – the Frauenkirche – now a cathedral, was constructed in only 20 years, starting in 1468; when Bavaria was reunited in 1506, Munich became its capital. The arts and politics became influenced by the court. During the 16th century, Munich was a centre of the German counter reformation, of renaissance arts. Duke Wilhelm V commissioned the Jesuit Michaelskirche, which became a centre for the counter-reform
Molecular self-assembly is the process by which molecules adopt a defined arrangement without guidance or management from an outside source. There are two types of self-assembly; these are intermolecular self-assembly. The term molecular self-assembly refers to intermolecular self-assembly, while the intramolecular analog is more called folding. Molecular self-assembly is a key concept in supramolecular chemistry; this is because assembly of molecules in such systems is directed through noncovalent interactions as well as electromagnetic interactions. Common examples include the formation of micelles, liquid crystal phases, Langmuir monolayers by surfactant molecules. Further examples of supramolecular assemblies demonstrate that a variety of different shapes and sizes can be obtained using molecular self-assembly. Molecular self-assembly allows the construction of challenging molecular topologies. One example is Borromean rings, interlocking rings wherein removal of one ring unlocks each of the other rings.
DNA has been used to prepare a molecular analog of Borromean rings. More a similar structure has been prepared using non-biological building blocks. Molecular self-assembly underlies the construction of biologic macromolecular assemblies in living organisms, so is crucial to the function of cells, it is exhibited in the self-assembly of lipids to form the membrane, the formation of double helical DNA through hydrogen bonding of the individual strands, the assembly of proteins to form quaternary structures. Molecular self-assembly of incorrectly folded proteins into insoluble amyloid fibers is responsible for infectious prion-related neurodegenerative diseases. Molecular self-assembly of nanoscale structures plays a role in the growth of the remarkable β-keratin lamellae/setae/spatulae structures used to give geckos the ability to climb walls and adhere to ceilings and rock overhangs. Molecular self-assembly is an important aspect of bottom-up approaches to nanotechnology. Using molecular self-assembly the final structure is programmed in the shape and functional groups of the molecules.
Self-assembly is referred to as a'bottom-up' manufacturing technique in contrast to a'top-down' technique such as lithography where the desired final structure is carved from a larger block of matter. In the speculative vision of molecular nanotechnology, microchips of the future might be made by molecular self-assembly. An advantage to constructing nanostructure using molecular self-assembly for biological materials is that they will degrade back into individual molecules that can be broken down by the body. DNA nanotechnology is an area of current research that uses the bottom-up, self-assembly approach for nanotechnological goals. DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information, to make structures such as complex 2D and 3D lattices and three-dimensional structures in the shapes of polyhedra.
These DNA structures have been used as templates in the assembly of other molecules such as gold nanoparticles and streptavidin proteins. The spontaneous assembly of a single layer of molecules at interfaces is referred to as two-dimensional self-assembly. One of the common examples of such assemblies are Langmuir-Blodgett monolayers and multilayers of surfactants. Non-surface active molecules can assemble into ordered structures as well. Early direct proofs showing that non-surface active molecules can assemble into higher-order architectures at solid interfaces came with the development of scanning tunneling microscopy and shortly thereafter. Two strategies became popular for the self-assembly of 2D architectures, namely self-assembly following ultra-high-vacuum deposition and annealing and self-assembly at the solid-liquid interface; the design of molecules and conditions leading to the formation of highly-crystalline architectures is considered today a form of 2D crystal engineering at the nanoscopic scale.
Supramolecular assembly Foldamer Macromolecular assembly Ice-nine Self-assembly of nanoparticles
Endohedral fullerenes called endofullerenes, are fullerenes that have additional atoms, ions, or clusters enclosed within their inner spheres. The first lanthanum C60 complex was synthesized in 1985 and called La@C60; the @ in the name reflects the notion of a small molecule trapped inside a shell. Two types of endohedral complexes exist: endohedral metallofullerenes and non-metal doped fullerenes. In a traditional chemical formula notation, a buckminsterfullerene with an atom was represented as MC60 regardless of whether M was inside or outside the fullerene. In order to allow for more detailed discussions with minimal loss of information, a more explicit notation was proposed in 1991, where the atoms listed to the left of the @ sign are situated inside the network composed of the atoms listed to the right; the example above would be denoted M@C60 if M were inside the carbon network. A more complex example is K2, which denotes "a 60-atom fullerene cage with one boron atom substituted for a carbon in the geodesic network, a single potassium trapped inside, two potassium atoms adhering to the outside."The choice of the symbol has been explained by the authors as being concise printed and transmitted electronically, the visual aspects suggesting the structure of an endohedral fullerene.
Doping fullerenes with electropositive metals takes place in an arc reactor or via laser evaporation. The metals can be transition metals like scandium, yttrium as well as lanthanides like lanthanum and cerium. Possible are endohedral complexes with elements of the alkaline earth metals like barium and strontium, alkali metals like potassium and tetravalent metals like uranium and hafnium; the synthesis in the arc reactor is however unspecific. Besides unfilled fullerenes, endohedral metallofullerenes develop with different cage sizes like La@C60 or La@C82 and as different isomer cages. Aside from the dominant presence of mono-metal cages, numerous di-metal endohedral complexes and the tri-metal carbide fullerenes like Sc3C2@C80 were isolated. In 1999 a discovery drew large attention. With the synthesis of the Sc3N@C80 by Harry Dorn and coworkers, the inclusion of a molecule fragment in a fullerene cage had succeeded for the first time; this compound can be prepared by arc-vaporization at temperatures up to 1100 °C of graphite rods packed with scandium oxide iron nitride and graphite powder in a K-H generator in a nitrogen atmosphere at 300 Torr.
Endohedral metallofullerenes are characterised by the fact that electrons will transfer from the metal atom to the fullerene cage and that the metal atom takes a position off-center in the cage. The size of the charge transfer is not always simple to determine. In most cases it is between 2 and 3 charge units, in the case of the La2@C80 however it can be about 6 electrons such as in Sc3N@C80, better described as +6@−6; these anionic fullerene cages are stable molecules and do not have the reactivity associated with ordinary empty fullerenes. They are stable in air up to high temperatures; the lack of reactivity in Diels-Alder reactions is utilised in a method to purify −6 compounds from a complex mixture of empty and filled fullerenes of different cage size. In this method Merrifield resin is modified as a cyclopentadienyl resin and used as a solid phase against a mobile phase containing the complex mixture in a column chromatography operation. Only stable fullerenes such as +6@−6 pass through the column unreacted.
In Ce2@C80 the two metal atoms exhibit a non-bonded interaction. Since all the six-membered rings in C80-Ih are equal the two encapsulated Ce atoms exhibit a three-dimensional random motion; this is evidenced by the presence of only two signals in the 13C-NMR spectrum. It is possible to force the metal atoms to a standstill at the equator as shown by x-ray crystallography when the fullerene is exahedrally functionalized by an electron donation silyl group in a reaction of Ce2@C80 with 1,1,2,2-tetrakis-1,2-disilirane. Martin Saunders in 1993 produced endohedral complexes He@C60 and Ne@C60 by pressurizing C60 to ca. 3 bar in a noble-gas atmosphere. Under these conditions about one out of every 650,000 C60 cages was doped with a helium atom; the formation of endohedral complexes with helium, argon and xenon as well as numerous adducts of the He@C60 compound was demonstrated with pressures of 3 kbars and incorporation of up to 0.1% of the noble gases. While noble gases are chemically inert and exist as individual atoms, this is not the case for nitrogen and phosphorus and so the formation of the endohedral complexes N@C60, N@C70 and P@C60 is more surprising.
The nitrogen atom is in its electronic initial state and is therefore to be reactive. N@C60 is sufficiently stable that exohedral derivatization from the mono- to the hexa adduct of the malonic acid ethyl ester is possible. In these compounds no charge transfer of the nitrogen atom in the center to the carbon atoms of the cage takes place. Therefore, 13C-couplings, which are observed easily with the endohedral metallofullerenes, could only be observed in the case of the N@C60 in a high resolution spectrum as shoulders of the central line; the central atom in these endohedral complexes is located in the center of the cage. While other atomic traps require complex equipment, e.g. laser cooling or magnetic traps, endohedral fullerenes represent an atomic trap, stable at room temperature and for an arbitrarily long time. Atomic or ion traps are of great interest since particles are present free from interaction with their environment
Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body. Sustained-release dosage forms are dosage forms designed to release a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects; this can be achieved through a variety of formulations, including liposomes and drug-polymer conjugates. Sustained release's definition is more akin to a "controlled release" rather than "sustained". Extended-release dosage consists of sustained-release and controlled-release dosage. SR maintains drug release over a sustained period but not at a constant rate. CR maintains drug release over a sustained period at a nearly constant rate. Sometimes these and other terms are treated as synonyms, but the United States Food and Drug Administration has in fact defined most of these as different concepts. Sometimes the term "depot tablet" is used by non-native speakers, but this is not found in any English dictionaries and is a literal translation of the term used in Swedish and some other languages.
Modified-release dosage and its variants are mechanisms used in tablets and capsules to dissolve a drug over time in order to be released slower and steadier into the bloodstream while having the advantage of being taken at less frequent intervals than immediate-release formulations of the same drug. For example, extended-release morphine enables people with chronic pain to only take one or two tablets per day. Most it refers to time dependent release in oral dose formulations. Timed release has several distinct variants such as sustained release where prolonged release is intended, pulse release, delayed release etc. A distinction of controlled release is that not only it prolongs action but it attempts to maintain drug levels within the therapeutic window to avoid hazardous peaks in drug concentration following ingestion or injection and to maximize therapeutic efficiency. In addition to pills and injectable drug carriers, forms of controlled release medicines include gels and devices and transdermal patches.
Examples of cosmetics, personal care and food science applications centre on odour or flavour release. The release technology scientific and industrial community is represented by the Controlled Release Society; the CRS is the worldwide society for delivery science and technologies. CRS serves more than 1,600 members from more than 50 countries. Two-thirds of CRS membership is represented by industry and one-third represents academia and government. CRS is affiliated with the Journal of Controlled Release and Drug Delivery and Translational Research scientific journals; the earliest SR drugs are associated with a patent in 1938 by Israel Lipowski, who coated pellets which led to coating particles. The science of controlled release developed further with more oral sustained-release products in the late 1940s and early 1950s, the development of controlled release of marine anti-foulants in the 1950s and controlled release fertilizer in the 1970s where sustained and controlled delivery of nutrients following a single application to the soil.
Delivery is effected by dissolution, degradation or disintegration of an excipient in which the active compound is formulated. Enteric coating and other encapsulation technologies can further modify release profiles. There is no industry standard for these abbreviations, confusion and misreading have sometimes caused prescribing errors. Clear handwriting is necessary. For some drugs with multiple formulations, putting the meaning in parentheses is advisable. A few other abbreviations refer to dose rather than release rate, they include ES and XS. Today, most time-release drugs are formulated so that the active ingredient is embedded in a matrix of insoluble substance such that the dissolving drug must find its way out through the holes. In some SR formulations, the drug dissolves into the matrix, the matrix physically swells to form a gel, allowing the drug to exit through the gel's outer surface. Micro-encapsulation is regarded as a more complete technology to produce complex dissolution profiles.
Through coating an active pharmaceutical ingredient around an inert core, layering it with insoluble substances to form a microsphere one can obtain more consistent and replicable dissolution rates in a convenient format that can be mixed and matched with other instant release pharmaceutical ingredients in to any two piece gelatin capsule. There are certain considerations for the formation of sustained-release formulation: If the pharmacological activity of the active compound is not related to its blood levels, time releasing has no purpose except in some cases, such as bupropion, to reduce possible side effects. If the absorption of the active compound involves an active transport, the development of a time-release product may be problematic; the half-life of the drug refers to the drug's elimination from the bloodstream which can be caused by metabolism and other forms of excretion. If the active compound has a long half-life, it is sustained on its own. If the active compound has a short half-life, it would require a large amount to maintain a prolonged effective dose.
In this case, a broad therape