Pseudo-polymorphism

Solid compounds can have four morphic states polymorphic, pseudo-polymorphic (solvates), amorphous, and desolvated solvates. Crystals usually exhibit narrow melting point ranges and defract light under an optical microscope. When a change in the arrangement of... 

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

The notion that mechanical stress may cause solid-to-solid phase transitions or other physicochemical transformations is well known in materials sciences. However, examples of molecular crystals undergoing mechanically induced phase transitions or polymorph — pseudo-polymorph transformations between crystalline phases are not very abundant some recent entries in the literature can be found in Ref. 74. 

Microscopy Polymorphs, pseudo polymorphs, and amorphous solids can be distinguished by morphology. 

Infrared, and more recently Raman spectroscopy, have been widely used for the qualitative and quantitative characterization of polymorphic compounds of pharmaceutical interest (for the sake of brevity, the term polymorphism will encompass polymorphs, pseudo-polymorphs, hydrates, and solvates). Since solid-state vibrational spectroscopy can be used to probe the nature of polymorphism on the molecular level, these methods are particularly useful in instances where full crystallographic characterization of polymorphism was not found to be possible. 

Photochemical stability of the solid compound is an important aspect when the drug is formulated as a suspension. Photochemical stability of a drug in the solid state can depend on the polymorphic/pseudo polymorphic form of the compound, which is demonstrated for chloroquine, mefloquine, and furosemide (Nord et al., 1997b Tpnnesen et al., 1997 De Villiers et al., 1992). The crystal structure, molecular conformations, and surface of the particles can thus influence photoreactivity of a suspended drug. When formulated as a suspension, the drug should be in the form of the stable polymorph. Transformation can occur between different crystal forms in the presence of a liquid, often accompanied by caking of the crystals (Martin, 1993). Photochemical stability of solids is further discussed in Chapter 16. 

Besides polymorphism, pseudo-polymorphism also exists. In pseudo-polymorphism, a substance is found in... 

The diffusion, location and interactions of guests in zeolite frameworks has been studied by in-situ Raman spectroscopy and Raman microscopy. For example, the location and orientation of crown ethers used as templates in the synthesis of faujasite polymorphs has been studied in the framework they helped to form [4.297]. Polarized Raman spectra of p-nitroaniline molecules adsorbed in the channels of AIPO4-5 molecular sieves revealed their physical state and orientation - molecules within the channels formed either a phase of head-to-tail chains similar to that in the solid crystalline substance, with a characteristic 0J3 band at 1282 cm , or a second phase, which is characterized by a similarly strong band around 1295 cm . This second phase consisted of weakly interacting molecules in a pseudo-quinonoid state similar to that of molten p-nitroaniline [4.298]. 

Bulk drug 13C, 31P, 1SN, 25Mg, 23Na Solid state structure elucidation, drug-excipient interaction studies (variable temperature), (pseudo)polymorphic characterization at the qualitative and quantitative level, investigation of hydrogen bonding with salt compounds... 

Tablets 13C, 31P Drug-excipient interaction studies, (pseudo)-polymorphic characterization at the qualitative and quantitative levels...

The term pseudo-polymorph is frequently used to describe the other types of solid phase that that are often encountered in the pharmaceutical sector. It includes the crystalline hydrates and solvates together with the amorphous or glass solid state. The structure and properties of these phases will be discussed in section 3.2. 

Gas-solid reactions and the relationship with solvation processes and the formation of crystal polymorphs and pseudo-polymorphs [15]. 

Molecular skeleton of the (UNUNj)4 ring in two crystalline polymorphs of [(C5Me5)2Uai-N)U(/i-N3)(C5Me5)2U pseudo-crown conformation observed for isomeric form A and pseudo-saddle observed for form B. The pair of r] -C5Me5 groups bonded to each uranium(IV) atom is not shown. From W. J. Evans, S. A. Kozimor and J. W. Ziller, Science 309, 1835-8 (2005). 

The donor (S, S)-3 forms two different polymorphs when it forms a salt with perchlorate anions, one of which shows a crystalline packing somewhat different to those described above, in which the donors form orthogonally oriented dimers in a sheet (k type packing) [37]. Pseudo-symmetry again prevails here, at the centre of the dimer, despite a slight homochiral twist at the central C = C bond. The salt is weakly metallic. Meanwhile, the compound 2... 

The controlled preparation and characterization of different crystal forms of the same substance has become one of the major issues of modern crystal engineering and solid-state chemistry. Even though the discovery of polymorphs of molecular crystals or of their diverse solvate forms (pseudo-polymorphs) is often serendipitous, crystal polymorphism can, to some extent, be controlled. The existence of more than one packing arrangement for the same molecular or ionic components) could be a major drawback for the purposed bottom-up construction of functional solids. Rather than attempting a thorough review of the subject, this... 

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