Crystalline polymorphs

Properties and Structure. Phosphoms(V) oxide, the extremely hygroscopic acid anhydride of the phosphoric acids, exists in several forms but is often referred to by its empirical formula, P2O3. Three crystalline polymorphs, two distinct Hquids, and several amorphous or glassy soHds are recogni2ed. Some properties of the various forms of phosphoric oxide are Hsted in Table 10. 

Phosphorus (like C and S) exists in many allotropic modifications which reflect the variety of ways of achieving catenation. At least five crystalline polymorphs are known and there are also several amorphous or vitreous forms (see Fig. 12.3). All forms, however, melt to give the same liquid which consists of symmetrical P4 tetrahedral molecules, P-P 225 pm. The same molecular form exists in the gas phase (P-P 221pm), but at high temperatures (above 800°C) and low pressures P4 is in equilibrium with the diatomic form P=P (189.5 pm). At atmospheric pressure, dissociation of P4 into 2P2 reaches 50% at 1800°C and dissociation of P2 into 2P reaches 50% at 2800°. 

Table 12.S Some properties of crystalline polymorphs of P2O5...

Chemical development Proof of structure and configuration are required as part of the information on chemical development. The methods used at batch release should be validated to guarantee the identity and purity of the substance. It should be established whether a drug produced as a racemate is a true racemate or a conglomerate by investigating physical parameters such as melting point, solubility and crystal properties. The physicochemical properties of the drug substance should be characterized, e.g. crystallinity, polymorphism and rate of dissolution. 

Ice I is one of at least nine polymorphic forms of ice. Ices II to VII are crystalline modifications of various types, formed at high pressures ice VIII is a low-temperature modification of ice VII. Many of these polymorphs exist metastably at liquid nitrogen temperature and atmospheric pressure, and hence it has been possible to study their structures without undue difficulty. In addition to these crystalline polymorphs, so-called vitreous ice has been found within the low-temperature field of ice I. It is not a polymorph, however, since it is a glass, i.e. a highly supercooled liquid. It is formed when water vapour condenses on surfaces cooled to below — 160°C. 

US patent 6,689,802, Polymorphs of an epothilone analog [100]. This invention describes two crystalline polymorphs, as well as mixtures of these, of an epothilone analog. Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them, and pharmaceutical dosage forms containing them. 

US patent 6,713,481, Crystalline antifungal polymorph [104]. This patent discloses the crystalline polymorph Form I of ( )-4-[4-[4-[4-[[(2R-cA)-5-(2,4-difluoro-phenyl)tetrahydro-5-( 1H-1,2,4-triazol- l-ylmethyl)furan-3-yl]methoxy]phenyl]-1 -piper azinyl]phenyl-2,4-dihydro-2-[(S)-l-ethyl-2(S)-hydroxylpropyl]-3H-l,2,4-triazol-3-one,... 

M. Brinkmann, G. Gadret, M. Muccini, C. Taliani, N. Masciocchi, and A. Sironi, Correlation between molecular packing and optical properties in different crystalline polymorphs and amorphous thin films of mer-Tris(8-hydroxyquinolinc)Aluminum(III), J. Am. Chem. Soc., 122 5147— 5157 (2000). 

Silica has 22 polymorphs, although only some of them are of geochemical interest—namely, the crystalline polymorphs quartz, tridymite, cristobahte, coesite, and stishovite (in their structural modifications of low and high T, usually designated, respectively, as a and jS forms) and the amorphous phases chalcedony and opal (hydrated amorphous silica). The crystalline polymorphs of silica are tectosilicates (dimensionality = 3). Table 5.68 reports their structural properties, after the synthesis of Smyth and Bish (1988). Note that the number of formula units per unit cell varies conspicuously from phase to phase. Also noteworthy is the high density of the stishovite polymorph. 

Chain Building. Both crystalline polymorphs of starch have the same fiber repeat of 1.05 nm and are built with the same unit a parallel stranded double-helix. Each strand has six glucose residues per turn in 2.1 nm and the two strands are related by a two-fold axis of symmetry this creates the apparent 1.05 nm fiber repeat. The chirality of the helices has been postulated to be either right-handed (12.13) or left-handed (14.15. ... 

Understanding the Crystalline Polymorphism in Native Starch. From this study, it is clear that the A and B forms have in common not only a double-helix but a... 

Crystalline (polymorphic / pseudo-polymorphic) amorphous forms... 

The solid-state properties like crystallinity, polymorphism (crystal structure), shape (morphology), and particle size of drugs are important in the stability, dissolution, and processibility of drugs. Some commonly used methods in solid-state studies include microscopy, hot stage microscopy with polarized light, x-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared FTIR/Raman, and solid-state NMR. 

Marchessault et at. (27) obtained weakly crystalline and oriented fibers(A) by extruding a 10% DMSO solution of crudlan into CH3OH at room temperature and washing it in water. They found that the same fiber annealed in water, under tension, at 140°C, in a sealed bomb, is of higher crystallinity and occured as two reversible crystalline polymorphs one at high relative humidity(B) and the other at humidities less than 20%(C). 

A systematic study of salting-out precipitation is carried out to obtain the operational limits within which this precipitation method can be applied for the production of fines (mean particle size <10 xm) with acceptable quality and productivity. The model substances glycine and sodium chloride are salted-out from their aqueous solutions by using ethanol as antisolvent. The main operational parameter is the initial supersaturation of the solutions. It is shown that the smallest particles can be produced at the limits of the metastability domain determined by three optional process parameters the initial solution concentration, the equilibrium solubility and the operational time. The product quality (crystallinity, polymorphic states, aggregation) and productivity considerably change with the operational conditions. 

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