Properties and Polymorphism

Materials may occur as amorphous substances without any definite structure or as crystalline particles with a definite structure and shape. Some materials may exist in more than one crystalline form (polymorph) and are described as exhibiting polymorphism. The type of crystal formed depends on the conditions, such as temperature and type of solvent, under which crystallization is induced. At a specific temperature or pressure, more than one polymorph can exist but only one will be thermodynamically stable. The less stable or metastable forms will be converted to the stable form with time. Studies show that it may take from minutes to years to revert to the stable lattice structure. 

The different crystalline forms of a material generally differ in many physical characteristics, such as solubility, melting point, optical and electrical properties, density, hardness, and stability. The use of metastable polymorphs frequently results in higher solubility and dissolution rates while the stable polymorphs are often more resistant to chemical degradation. It is obvious that any change in the crystalline form will affect the therapeutic efficacy of a pharmaceutical product. Therefore, 

A number of techniques may be used to identify the crystalline form of a material. It is advisable to employ more than one method in the analysis as the use of only one method has been found to be unreliable at times. 

The concentration of the metastable polymorph is noted to increase much more rapidly at the initial period of the dissolution study and then drop to that of the stable polymorph. For the stable polymorph, the dissolution profile just increases gradually to a plateau. The solubility of the metastable form is indicated by the peak of its dissolution curve. In some cases, the metastable polymorph does not revert readily to the stable form. The dissolution curve of such a metastable form lies above that of the stable form, indicating that the former is more soluble (Fig. 5B). The plateau of each curve indicates the solubility of the respective polymorph. 

Conventional X-ray diffraction method cannot distinguish polymorphs which have relatively small crystallites because of the low resolution of diffractometers. Synchrotron sources have been employed to obtain high-resolution electron diffraction patterns which enable differentiation of such polymorphs (18). The development of very sensitive charge-coupled detectors (CCD) has allowed electron diffraction patterns to be recorded in a few seconds using very low electron currents. 

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Ingelman-Sundberg M. Human drug metabolising cytochrome P450 enzymes properties and polymorphisms. Naunyn Schmiedebergs Arch Pharmacol 2004 369 89-104. 

The unique dielectric properties and polymorphism of PVDF are the source of its high piezoelectric and pyroelectric activity.75 The relationship between ferroelectric behavior, which includes piezoelectric and pyroelectric phenomena and other electrical properties of the polymorphs of polyvinylidene fluoride, is discussed in Reference 76. 

J. L. Hoard and R. E. Hughes, Elemental Boron and Compoimds of High Boron Content Structure, Properties and Polymorphism, in The Chemistry of Boron and Its Compoimds , ed. E. L. Muetterties, Wiley, New York, 1967, p. 25. 

There are a number of additional sources for consultation on information on polymorphism of particular compounds. From 1948 to 1961, McCrone edited a regular column in Analytical Chemistry entitled Crystallographic Data , in which were published the details on crystal growth, physical properties, and polymorphic behaviour of approximately 200 compounds. The series was undertaken at the time because optical crystallography is neglected as an analytical tool because too few compounds have been described , and with the desire to ... initiate a process which [would] enable a group of crystallographers to complete the tabulation of crystal data for most... 

Terao, H., Itoh, Y, Ohno, K., Isogai, M., Kakuta, A. andMukoh, A. (1990). 2nd order nonlinear optical properties and polymorphism of benzophenone derivatives. Opt. Commun., 74, 451-3. [213]... 

Paulechka YU, Blokhin AV, Kabo GJ et al. (2007) Thermodynamic properties and polymorphism of l-alkyl-3-methylimidazolium bis(triflamides). J Chem Thermodyn 39 866-877... 

An intriguing property of PFs is their ability to form liquid crystalline phases [38,39]. Besides the different mesophases which are classified as nematic, poly(9,9-dioctyl)fluorene (PFO) shows several solid-state packing properties and polymorphs. The pioneering work of Grell et al. showed how solvent swelling and thermal cycling could be used to control the solid-state packing in PFO thin films [38,40]. In addition, the different phases show remarkably diverse photophysical properties, which have tremendous... 

LeBoeuf, R.C., Puppione, Dl,., Schumaker, VJ4., and Lusis, A J. (1983) Genetic Control of Lipid Transport in Mice. I. Structural Properties and Polymorphisms of Plasma Lipoproteins, J. Biol. Chem. 258,5063-5070. 

POLYMORPHS OF IRON(III) OXIDE, THEIR CRYSTAL STRUCTURES, MAGNETIC PROPERTIES, AND POLYMORPHOUS PHASE TRANSFORMATIONS... 

The crystallization properties and polymorphism are dependent on the chain architecture. In fact, chains with a regular constitution and COTifiguration are generally able to adopt low energy conformations with a regular and periodic repetition of the monomeric imits along the chain axis, and therefore, they are also more able to crystallize than less regular chains (De Rosa and Auriemma 2013). 

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. 

Some electrical properties are shown in Table 3. Values of other parameters have been pubflshed (146). Polymorphism of the PVDF chains and the orientation of the two distinct dipole groups, —CF2— and —CH2—, rather than trapped space charges (147) contribute to the exceptional dielectric properties and the extraordinarily large piezoelectric and pyroelectric activity of the polymer (146,148,149). 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

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. 

Titanium dioxide exists in nature as three different polymorphs rutile, anatase and brookite. This material has been extensively studied during the last few decades due to its interesting physical properties and numerous technological applications. Rutile and anatase (a popular white pigment) are widely used in photocataly s and as sensors. Both of them have had new structural and electronic applications suggested recently (see for a review). 

In this article some literature studies together with studies conducted recently in our laboratories on the crystalline and molecular structure of polymorphic polymers are reviewed, also with the aim of showing possible influences of the polymorphism on the properties and, as a consequence, on the applications of polymeric materials. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

Microemulsions and Related Systems Formulation, Solvency, and Physical Properties, edited by Maurice Bourrel and Robert S. Schechter Crystallization and Polymorphism of Fats and Fatty Acids, edited by Nissim Garti and Kiyotaka Sato... 

Progress in molecular biology has provided a new perspective. Techniques such as the polymerase chain reaction and single-strand conformation polymorphism analysis have greatly facilitated the molecular analysis of erythroenzymopathies. These studies have clarified the correlation between the functional and structural abnormalities of the variant enzymes. In general, the mutations that induce an alteration of substrate binding site and/or enzyme instability might result in markedly altered enzyme properties and severe clinical symptoms. 

US patent 6,723,728, Polymorphic and other crystalline forms cis-FTC [106], The present invention relates to polymorphic and other crystalline forms of (—)-and ( )-cA-(4-amino-5-fluoro-l-(2-(hydroxymethyl)-l,3-oxathiolan-5-yl)-2(lH)-pyrimidinone, or FTC) [106]. Solid phases of (—)-cz>FTC that were designated as amorphous (—)-FTC, and Forms II and III were found to be distinguishable from Form I by X-ray powder diffraction, thermal analysis properties, and their methods of manufacture. A hydrated crystalline form of ( )-cA-FTC and a dehydrated form of the hydrate, were also disclosed, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction, thermal properties, and their methods of manufacture. These FTC forms can be used in the manufacture of other forms of FTC, or as active ingredients in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B. 

Almost without exception, all modern laser printers now use titanyloxy-phthalocyanine, type IV polymorph (47), as the CGM. Unlike copper phthalocyanine, which is planar (Figure 7) titanyloxy-phthalocyanine has a shallow shuttlecock shape (Figure 8). This has a subtle effect on the packing of the molecules, which contributes to its excellent performance as a CGM. Indeed, titanyloxy-phthalocyanine has the best combination of properties and is unlikely to be surpassed.37... 

Disregarding such chemical-specific properties as dissociation constants (in the case of ionic compounds), particle size, and polymorphism, as well as side effects of viscosity, binding to vehicle components, complex formulation, and the like, the following formulation principles arise ... 

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