Hydration and solvation

The way in which solute molecules interact with the water molecules of the solvent is cmcial to determining their affinity for the 

Solvation is the general term used to describe the process of binding of solvent to solute molecules. If the solvent is water, the process is hydration. In a solution of sucrose (XIII), six water molecules are bound to each sucrose molecule with such avidity that water and sucrose move as a unit in solution, and the extent of hydration can therefore be measured by hydrodynamic techniques. 

Chemically very similar molecules such as mannitol (XIV), sorbitol (XV) and inositol have very different affinities for water. The solubility of sorbitol in water is about 3.5 times that of mannitol. 

Most favourable hydration occurs when there is an equatorial -OH group on pyranose sugars. This is thought to be due to the compatibility of the equatorial -OH with the organised structure of water in bulk. Axial 

Hydration of ionic species water structure breakers and structure makers 

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Hydration and solvation have also been studied by conductivity measurements these measurements give rise to an effective radius for the ion, from which a hydration number can be calculated. These effective radii are reviewed in the next section. 

Low sulfate selectivity of the ion-selective electrodes (ISE) based on lipophilic quaternary ammonium salts (QAS) is usually explained by unfavorable ratio of sulfate hydration and solvation energies. We have been shown that another reason does exist as well namely, low efficiency of sulfate-QAS cation interaction caused by steric hindrance for simultaneous approach of two QAS cations, containing four long-chain hydrocarbon substituents, to sulfate ion. 

Oostenbrink, C., Villa, A., Mark, A. E., Van Gunsteren, W. F. A biomolecular force field based on the free enthalpy of hydration and solvation the GROM OS force-field parameter sets 53A5 and 53A5. J. Comput. Chem. 2004, 25, 1555-1575. 

K. R. Morris, Structural aspects of hydrates and solvates, in Polymorphism in Pharmaceutical Solids (H. G. Brittain, Ed.), Marcel Dekker, New York, 1999, p. 132. 

In principle, Gibbs free energies of transfer for trihalides can be obtained from solubilities in water and in nonaqueous or mixed aqueous solutions. However, there are two major obstacles here. The first is the prevalence of hydrates and solvates. This may complicate the calculation of AGtr(LnX3) values, for application of the standard formula connecting AGt, with solubilities requires that the composition of the solid phase be the same in equilibrium with the two solvent media in question. The other major hurdle is that solubilities of the trichlorides, tribromides, and triiodides in water are so high that knowledge of activity coefficients, which indeed are known to be far from unity 4b), is essential (201). These can, indeed, be measured, but such measurements require much time, care, and patience. 

The enthalpies of solution and solubilities reviewed here provide much of the experimental information required in the derivation of single-ion hydration and solvation enthalpies, Gibbs free energies, and entropies for scandium, yttrium, and lanthanide 3+ cations. 

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. 

Ab initio methods for polymorph, hydrate and solvate prediction are highly prized by the industry and good progress has been made in this field in recent years. This work is still a number of years from routine commercial application however, and polymorph screening experiments together with crystal structure determination, remain critical tasks for today s Pharmaceutical companies. 

The stroboscopic pulse radiolysis with the single bunch electron pulse instead of pulse trains started in Argonne National Laboratory in 1975 [54]. The research fields have been extended by the stroboscopic pulse radiolysis with the picosecond single electron bunch, although most of researches had been limited to hydrated and solvated electrons in the aqueous and alcoholic solutions. This system was unable to study the kinetics of the geminate ion recombination in liquid hydrocarbons until the modification of the Argonne linac in 1983, which made possible the quality measurements of the weak absorption. 

Having identified and characterised all known polymorphs, hydrates and solvates of an API it is important to determine the relationship between all known forms. Conversion of one form to another can be caused by common... 

As will be discussed below, hydrates and solvates represent a relevant portion of the known polymorphic forms for many substances. While representing a complication in the study of polymorphism, their existence can be extremely advantageous. It is not uncommon to have several forms of the same molecule or salt that differ in the degree of solvation and the number and type of solvent molecules. The problem is complicated by the often nonstoichiometric, fractional or variable presence of solvent molecules. 

Infrared Characterization of polymorphs based on functional groups characterization of hydrates and solvates... 

A survey by this author of the 1 October 2000 release of the CSD ( 225 000 entries) yielded 6353 hits for the qualifier form , 1045 hits for the qualifier phase 528 hits for the qualifier polymorph , 201 hits for the qualifier modification , 28 342 hits for the qualifier solvate and21 132 hits for the qualifier hydrate . Of course, the last two numbers give no indication of whether the materials are polymorphic and none of these statistics indicate the instances for which the structures of more than one form have been determined. The data for hydrates and solvates from the CSD may be considered quite reliable, since molecules of solvation are usually positively identified in the course of a crystai structure determination. The frequency of polymorphs, however, is likely to be underestimated, since many crystal structures of polymorphic systems, or what later are discovered to be polymorphic systems, are reported without making note of that fact. If the structure of only one member of a polymorphic family has been reported, then there may not be any reference to the polymorphism in the CSD. References to drugs discovered prior to 1971 that form solvates have been compiled, along with a separate summary of the thermomicroscopic behaviour of drug hydrates by Byrn et al. (1999). 

Other important forces, including hydration and solvation forces associated with the tendency of molecules or ions to bind tightly to surfaces, as well as hydrophobic and hydrophilic forces and other specific interactions, are present in complex fluids. These forces become important at separations of a couple of nanometers. As discussed in Chapter 7, such forces can influence the rheological properties of suspensions of particles in near contact. 

Lyotropic liquid crystals differ from thermotropic liquid crystals. They are formed by mesogens that are not the molecules themselves but their hydrates or solvates as well as by associates of hydrated or solvated molecules. In presence of water or a mixture of water and an organic solvent as the most important solvents for drug molecules, the degree of hydration or solvation depends on the amphiphilic properties of a drug molecule. Hydration—and solvation—of the mostly rod-shaped molecule results in different geometries such as cone and cylinder (Fig. 3). ... 

TGA may also be used to characterize hydrates and solvates, as outlined in more detail below. This represents one of the major uses of the technique, as the operator may not only detect the hydrate but may also determine both the stoichiometry of the binary system and (he binding strength of the solvent within the matrix. The third basic use of... 

Hydrates and solvates can be prepared by crystallization in water or an organic solvent or by conversion of the anhydrous material through moisture or solvent adsorption. In quality control testing, hydrates or solvates are identified by the assay of water of crystallization or solvent found in the crystal. Water determination is achieved by Karl Fischer titration or a coulometric method or loss-on-drying by the USP method. In the preformulation study, the hot stage microscope is a useful simple technique. TGA can also be an informative tool, as shown in Figure 15. 

Whereas the NMR spectra of liquids are very sharp, the absorption lines of solids are broad and are referred to as broadline NMR. The major application of broadline NMR is in the measurement of the internuclear distances and other crystal parameters important in the study of polymorphism as well as hydrates and solvates. Solid NMR may overcome the drawbacks of using X-ray diffraction for crystal structure determination. As a single crystal is required for X-ray study, material that cannot be crystallized may not be applied. On the other hand, powder samples are suitable for generating a spectrum to illustrate the crystal structure by the solid NMR technique. 

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