Solvates solid-state properties

The phenomenon of pseudopolymorphism is also observed, i.e., compounds can crystallize with one or more molecules of solvent in the crystal lattice. Conversion from solvated to nonsolvated, or hydrate to anhydrous, and vice versa, can lead to changes in solid-state properties. For example, a moisture-mediated phase transformation of carbamazepine to the dihydrate has been reported to be responsible for whisker growth on the surface of tablets. The effect can be retarded by the inclusion of Polyoxamer 184 in the tablet formulation [61]. 

Unfortunately, our understanding of the physics and chemistry of salt formation is not yet at a stage where we can predict a priori the physicochemical properties of a proposed salt. A particular problem in this regard is the formation of a range of salt polymorphs and/or solvates. While qualitative/semiempi-rical guidelines have been developed, the selection process is still largely experiment based. It is to be hoped that developments in computational methods will soon lead to the more accurate prediction of bio-pharmaceutically relevant solid-state properties that will ultimately simplify the task of appropriate salt selection. 

The solubility is most often experimentally determined from the dmg concentration in the liquid phase after adding excessive amounts of a solid dmg substance to the test medium. This apparent solubility is affected by the solid-state properties of the dmg, for example, polymorphs, solvates, impurities, and amorphous content. An equilibrium with the thermodynamically most stable solid-state form, being the least... 

Examination of the residual solid from solubility samples is one of the most important but often overlooked steps in solubility determinations. Powder X-ray diffraction (PXRD) is the most reliable method to determine whether any solid state form change has occurred during equilibration. The sample should be studied both wet and dry to determine if any hydrate or solvate exists. Thermal analysis techniques such as differential scanning calorimetry (DSC) can also be used to identify any solid-state transformations, although they may not provide as definitive an answer as the PXRD method. Other methods useful in identifying any solid-state changes include microscopy, Raman and infrared spectroscopy, and solid-state NMR (Brittain, 1999). When changes in solid-state properties are identified in solubility studies, it is important to link the new properties to the properties of known crystal forms so the solubility result can be associated with the appropriate crystal form. 

H-K Chan, S Venkataram, DJW Grant, Y-E Rahman. Solid state properties of an oral iron chelator, l,2-dimethyl-3-hydroxy-4-pyridone and its acetic acid solvate. I Physicochemical characterization intrinsic dissolution rate and solution thermodynamics. J Pharm Sci 80 677-685, 1991. 

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. 

Mott transition, 25 170-172 paramagnetic states, 25 148-161, 165-169 continuum model, 25 159-161 ESR. studies, 25 152-157 multistate model, 25 159 optical spectra, 25 157-159 and solvated electrons, 25 138-142 quantitative theory, 25 138-142 spin-equilibria complexes, 32 2-3, see also specific complex four-coordinated d type, 32 2 implications, 32 43-44 excited states, 32 47-48 porphyrins and heme proteins, 32 48-49 electron transfer, 32 45-46 race-mization and isomerization, 32 44—45 substitution, 32 46 in solid state, 32 36-39 lifetime limits, 32 37-38 measured rates, 32 38-39 in solution, 32 22-36 static properties electronic spectra, 32 12-13 geometric structure, 32 6-11 magnetic susceptibility, 32 4-6 vibrational spectra, 32 13 summary and interpretation... 

Besides regulatory importance, salts, polymorphs, and hydrates/solvates have clear novelty and patentability considering their different chemical compositions or distinguishable solid state ( fon Raumer et al., 2006). Those new forms can affect not only their processibilities, such as crystallization,Lltration, and compression, but also their biological properties, such as solubility and bioavailability. Besides, the manufacturing processes for those forms are often innovative, and thus patentable. 

It would have been difficult to find these kinds of relations with inorganic materials proper. The organic molecule is unique in that its physical properties may be changed in a continuous way by small modifications in its structure or by complexation with different metal ions. Another advantage is the fact that solid state effects are of smaller importance, and catalytic properties of the solid phase may be compared with physical properties in solution. In particular an extended jr-electron system works as a catalytic entity in itself, irrespective of whether it is surrounded by other molecules of its kind (solid phase) or solvating molecules (solutions). 

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