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Encyclopedia > Polymorphism (materials science)

When polymorphism exists as a result of difference in crystal packing it is called packing polymorphism. Polymorphism can also result from the existence of different conformers of the same molecule in conformational polymorphism. In pseudopolymorphism the different crystal types are the result of hydration or solvation. An example of an organic polymorph is glycine which is able to form monoclinic and hexagonal crystals. Conformational isomerism is the phenomenon of molecules with the same structural formula but different conformations (conformers) of atoms about a rotating bond. ... In chemistry, hydration is the condition of being combined with water. ... Solvation is the attraction and association of molecules of a solvent with molecules or ions of a solute. ... For the plant, see Glycine (plant). ... In crystallography, the monoclinic crystal system is one of the 7 lattice point groups. ... A regular hexagon A hexagon (also known as sexagon) is a polygon with six edges and six vertices. ...

An analogous phenomenon for amorphous materials is polymorphism, when a substance can take on several different amorphous modifications. An amorphous solid is a solid in which there is no long-range order of the positions of the atoms. ... In general, polymorphism describes multiple possible states for a single property (it is said to be polymorphic). ...

## Background

In terms of thermodynamics, there are two types of polymorphism. For a monotropic system, a plot of the free energy of the various polymorphs against temperature do not cross before all polymorphs melt - in other words, any transition from one polymorph to another will be irreversible. For an enantiotropic system, a plot of the free energy against temperature shows a crossing point before the various melting points, and it may be possible to convert reversibly between the two polymorphs on heating and cooling.

Despite the potential implications polymorphism is not always well understood. In 2006 a new crystal form was discovered of maleic acid 124 years after the first crystal structure determination [1]. Maleic acid is a chemical manufactured on a very large scale in the chemical industry and is a salt forming component in medicine. The new crystal type is produced when a caffeine - maleic acid co-crystal (2:1) is dissolved in chloroform and when the solvent is allowed to evaporate slowly. Whereas form I has monoclinic space group P21/c, the new form has space group Pc. Both polymorphs consist of sheets of molecules connected through hydrogen bonding of the carboxylic acid groups but in form I the sheets alternate with respect of the net dipole moment whereas in form II the sheets are oriented in the same direction. Maleic acid or (Z)-Butenedioic acid or cis-butenedioic acid or malenic acid or maleinic acid or toxilic acid is an organic compound which is a dicarboxylic acid (molecule with two carboxyl groups). ... Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. ... For the song Chloroform by Spoon, see A Series of Sneaks Chloroform, also known as trichloromethane and methyl trichloride, is a chemical compound with formula CHCl3. ... In crystallography, the monoclinic crystal system is one of the 7 lattice point groups. ... The space group of a crystal is a mathematical description of the symmetry inherent in the structure. ... Snapshot from a simulation of liquid water. ... Structure of a carboxylic acid The 3D structure of the carboxyl group A space-filling model of the carboxyl group Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted... This article is about the electromagnetic phenomenon. ...

1,3,5-Trinitrobenzene is more than 125 years old and was used as an explosive before the arrival of the safer 2,4,6-trinitrotoluene. Only one crystal form of 1,3,5-trinitrobenzene has been known in the space group Pbca. In 2004, a second polymorph was obtained in the space group Pca2(1) when the compound was crystallized in the presence of an additive, trisindane. This experiment shows that additives can induce the appearance of polymorphic forms. [2] Trinitrotoluene (TNT, or Trotyl) is a pale yellow crystalline aromatic hydrocarbon compound that melts at 354 K (178 Â°F, 81 Â°C). ...

## Polymorphism in pharmaceuticals

Polymorphism is important in the development of pharmaceutical ingredients. Many drugs are receiving regulatory approval for only a single crystal form or polymorph. In a classic patent case the pharmaceutical company GlaxoSmithKline defended its patent for the polymorph type II of the active ingredient in Zantac against competitors while that of the polymorph type I had already expired. Polymorphism in drugs can also have direct medical implications. Medicine is often administered orally as a crystalline solid and dissolution rates depend on the exact crystal form of a polymorph. An active ingredient, also active pharmaceutical ingredient (or API), is the substance in drug that is pharmaceutically active. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... A regulation is a legal restriction promulgated by government administrative agencies through rulemaking supported by a threat of sanction or a fine. ... A patent is a set of exclusive rights granted by a state to a patentee (the inventor or assignee) for a fixed period of time in exchange for the regulated, public disclosure of certain details of a device, method, process or composition of matter (substance) (known as an invention) which... GlaxoSmithKline plc (LSE: GSK NYSE: GSK) is a British based pharmaceutical, biologicals, and healthcare company. ... Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). ... medicines, see medication and pharmacology. ... Dissolution can have the following meanings : In chemistry, it is the process of dissolving a substance into a liquid. ...

Cefdinir is a drug appearing in 11 patents from 5 pharmaceutical companies in which a total of 5 different polymorphs are described. The original inventor Fuijsawa now Astellas (with US partner Abbott) extended the original patent covering a suspension with a new anhydrous formulation. Competitors in turn patented hydrates of the drug with varying water content which were importantly only described with basic techniques such as infrared spectroscopy and XRPD, a practise critisized by in one review [3] because these techniques at the most suggest a different crystal structure but are unable to specify one. These techniques also tend to overlook chemical impurities or even co-components. Abbott researchers realized this the hard way when in one patent application it was ignored that their new cefdinir crystal form was in fact that of a pyridinium salt. The review also questioned whether the polymorphs offered any advantages to the existing drug something clearly demanded in a new patent. Cefdinir (marketed by Abbott Laboratories under the brand name OmnicefÂ®) is a semi-synthetic, broad-spectrum antibiotic in the third generation of the cephalosporin class, proven effective for common bacterial infections of the ear, sinus, throat, and skin. ... Astellas Pharma Inc. ... Abbott Laboratories (NYSE: ABT) is a diversified pharmaceuticals and health care company. ... Flour suspended in water In chemistry, a suspension is a colloidal dispersion (mixture) in which a finely-divided species is combined with another species, with the former being so finely divided and mixed that it doesnt rapidly settle out. ... As a general term, a substance is said to be anhydrous if it contains no water. ... Hydrate is a term which means different things in inorganic chemistry and organic chemistry. ... Infrared spectroscopy (IR Spectroscopy) is the subset of spectroscopy that deals with the infrared region of the electromagnetic spectrum. ... Powder diffraction is a scientific technique using X-Ray or neutron diffraction on powder or microcrystalline samples for structural characterization of materials. ... Pyridinium cation Pyridinium refers to the cationic form of pyridine. ...

Polymorphism has also been reported for acetylsalicylic acid [4], however this has been questioned recently.[5] A purportedly new crystal type was found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile. This so-called form II is only stable at 100 K and reverts back to form I at ambient temperature. In the (unambiguous) form I two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds and in the newly claimed form II each salicylic molecule forms the same hydrogen bonds but then with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups both polymorphs form identical dimer structures. The matter of aspirin polymorphism still appears unsettled. A very old bottle of Aspirin Aspirin or acetylsalicylic acid is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ... Levetiracetam (brand name: KeppraÂ®) is an anticonvulsant medication used to treat epilepsy. ... Acetonitrile is an organic molecule, often used as a solvent, with the chemical formula of CH3CN. Also known as methyl cyanide, it is the simplest of the organic nitriles. ... The Kelvin scale is a thermodynamic (absolute) temperature scale where absolute zeroâ€”the lowest possible temperature where nothing could be colder and no heat energy remains in a substanceâ€”is defined as zero kelvin (0 K). ... Sucrose, or common table sugar, is composed of glucose and fructose. ... Acetyl is the radical of acetic acid. ... In chemistry a methyl-group is a hydrophobic Alkyl functional group which is derived from methane (CH4). ... Carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom. ... Snapshot from a simulation of liquid water. ... Structure of a carboxylic acid The 3D structure of the carboxyl group A space-filling model of the carboxyl group Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted...

## Trivia

Walter McCrone stated that every compound has different polymorphic forms, and that, in general, the number of forms known for a given compound is proportional to the time and money spent in research on that compound. Dr. Walter Cox McCrone (1916-2002) was an American chemist who was considered a leading expert in microscopy. ...

Crystal Polymorphs can disappear. There have been cases of individual laboratories growing one crystal form. They then grow a different crystal form, and are unable to make the first form again. Alternatively, they find that they can make the first form again but it now converts to the second form over time. The drug Paroxetine was subject to a law suit that hinged on such a pair of polymorphs (A link to a discussion of cases in Canada and the US has been given below). An example is known when a so-called 'disappeared' polymorph re-appeared after 40 years. These so-called 'disappearing' polymorphs are probably metastable kinetic forms. Paroxetine or paroxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI) antidepressant. ...

## References

1. ^ Graeme M. Day, Andrew V. Trask, W. D. Samuel Motherwell and William Jones (2006). "Investigating the latent polymorphism of maleic acid". Chemical Communications 1: 54 - 56. DOI:10.1039/b513442k.
2. ^ Thallapally PK, Jetti RKR, Katz AK (2004). "Polymorphism of 1,3,5-trinitrobenzene induced by a trisindane additive". Angewandte Chemie International Edition 43 (9): 1149-1155.
3. ^ Polymorphisms and Patent, Market, and Legal Battles: Cefdinir Case Study Walter Cabri, Paolo Ghetti, Giovanni Pozzi, and Marco Alpegiani Org. Process Res. Dev.; 2007; 11(1) pp 64 - 72; (Review) DOI:10.1021/op0601060
4. ^ Peddy Vishweshwar, Jennifer A. McMahon, Mark Oliveira, Matthew L. Peterson, and Michael J. Zaworotko (2005). "The Predictably Elusive Form II of Aspirin". J. Am. Chem. Soc. 127 (48): 16802 - 16803. DOI:10.1021/ja056455b.
5. ^ Andrew D. Bond, Roland Boese, Gautam R. Desiraju (2007). "On the Polymorphism of Aspirin". Angewandte Chemie International Edition. DOI:10.1002/anie.200602378.

Chemical Communications or ChemComm is a is a peer-reviewed scientific journal in the chemical sciences published since 1996 by the Royal Society of Chemistry. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Angewandte Chemie or Angewandte Chemie International Edition is the chemistry journal of the Gesellschaft Deutscher Chemiker (Society of German Chemists). ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Angewandte Chemie or Angewandte Chemie International Edition is the chemistry journal of the Gesellschaft Deutscher Chemiker (Society of German Chemists). ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

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