Polymorphs preparation

Firsich, D. W. (1984). Energetic material separations and specific polymorph preparation via thermal gradient sublimation. J. Hazard. Mater., 9, 133-7. [294]... 

Toxicology batches (drug candidate) Meeting deadline is primary concern, to reach go/no go decision points during API development. Note that animals may be grown in advance of such studies. Invest time to determine and prepare desired final form (salt, polymorph). Prepare high-quality material, but not ultra-pure. If tox studies are conducted on material of an unrealistically high purity, subsequent tox studies will be needed to qualify batches of lower quality. 

Tozuka Y, Kawada D, Oguchi T, Yamamoto K. Supercritical carbon dioxide treatment as a new method for polymorph preparation of deoxycholic acid. AAPS Pharm Sci 2002 4(4). 

Many molecules are obtained and used in a crystalline form, the nature of which can have e significant impact on their properties and behaviour. Moreover, it is sometimes possible foi a given material to exist in more than one crystalline form, depending upon the conditions under which it was prepared. This is the phenomenon of polymorphism. This can be important because the various polymorphs may themselves have different properties. It is Iberefore of interest to be able to predict the three-dimensional atomic structure(s) that a gi en molecule may adopt, for those cases where it is difficult to obtain experimental data and also where one might wish to prioritise molecules not yet synthesised. 

In addition to the three principal polymorphs of siUca, three high pressure phases have been prepared keatite [17679-64-0] coesite, and stishovite. The pressure—temperature diagram in Figure 5 shows the approximate stabiUty relationships of coesite, quart2, tridymite, and cristobaUte. A number of other phases, eg, siUca O, siUca X, sihcaUte, and a cubic form derived from the mineral melanophlogite, have been identified (9), along with a stmcturaHy unique fibrous form, siUca W. 

Anatase and mtile are produced commercially, whereas brookite has been produced by heating amorphous titanium dioxide, which is prepared from an alkyl titanate or sodium titanate [12034-34-3] with sodium or potassium hydroxide in. an autoclave at 200—600°C for several days. Only mtile has been synthesized from melts in the form of large single crystals. More recentiy (57), a new polymorph of titanium dioxide, Ti02(B), has been demonstrated, which is formed by hydrolysis of K Ti O to form 20, followed by subsequent calcination/dehydration at 500°C. The relatively open stmcture... 

Bismuth Penta.fIuoride, Bismuth(V) fluoride consists of long white needles that have been shown to have the same stmcture as the body-centered, tetragonal a-polymorph of uranium hexafluoride. The density of the soHd is 5.4 g/mL at 25°C. The soHd consists of infinite chains of trans-bridged BiF polyhedra dimers and trimers are present in the vapor phase (22). Bismuth pentafluoride may be prepared by the fluorination of BiF or... 

Attachment of a hot or cold stage to the ordinary microscope stage allows the specimen to be observed while the temperature is changed slowly, rapidly, or held constant somewhere other than ambient. This technique is used to determine melting and freezing points, but is especially useful for the study of polymorphs, the determination of eutectics, and the preparation of phase diagrams. 

We now consider other homocyclic polymorphs of sulfur containing 6 - 20 S atoms per ring. A rhombohedral form, t-sulfur, was first prepared by M. R. Engel in 1891 by the reaction of concentrated HCl on a saturated solution of thiosulfate HS2O3 at 0°. It was shown to be... 

HgS is polymorphic. The red a-form is the mineral cinnabar, or vermilion, which has a distorted rock-salt structure and can be prepared from the elements. )3-HgS is the rare, black, mineral metacinnabar which has the zinc-blende structure and is converted by heat to the stable a-form. In the laboratory the most familiar form is the highly insoluble black precipitate obtained by the action of HzS on aqueous solutions of Hg. HgS is an unreactive substance, being attacked only by cone HBr, HI or aqua regia. HgSe and... 

Two polymorphic forms of 3- 2-[4-(6-fluorobenzisoxazol-3-yl)-l,2,3,6-tetrahydropyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n] pyrimidin-4-one (137 R = H) were prepared (99MIP1). Racemic 9-hydroxy-2-methyl-3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-l,2,3,6-tetrahydro-l-pyridyl] ethyl -6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidin-4-one was resolved into its (R)- and (5)-isomers (OOMIPIO). 

Various polymorphs have been reported for SnS with band gap widths in the range 1.0-1.5 eV, depending on the preparation method. The a-SnS (herzenbergite) is the most frequently occurring phase and is a p-type semiconductor with a direct optical transition at 1.3 eV and a high absorption coefficient (> 10" cm ). The orthorhombic S-SnS phase possesses a direct gap between 1.05 and 1.09 eV. 

Which polymorphic form of a compound is formed depends on the preparation and crystallization conditions method of synthesis, temperature, pressure, kind of solvent, cooling or heating rate, crystallization from solution, fusion or gas phase, and presence of seed crystals are some of the factors of influence. 

Polymorphs are different crystal forms of the same compound [55], They are usually prepared by crystallization of the drug from different solvents under diverse conditions. However, exposure to changes in temperature, pressure, relative humidity, and comminution which are encountered in processes such as drying, granulation, milling, and compression may also lead to polymorphic transformations. 

The surface phase diagram of vanadium oxides on Rh(l 11) has been investigated in a series of papers of our group [4, 18, 19, 90, 101-103]. It is characterized by pronounced polymorphism and many different oxide structures have been detected as a function of coverage and growth temperature. The vanadium oxide structures for coverages up to the completion of the first monolayer formed on Rh(l 11) under the different preparation conditions may be subdivided into highly oxidized phases... 

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