Hydration/solvation

The important role of thermodynamics in complex formation, ionic medium effects, hydration, solvation, Lewis acid-base interactions, and chelation has been presented in this chapter. Knowledge of these factors are of great value in understanding solvent extraction and designing new and better extraction systems. 

Thus from solubility parameters, which are specific for the various solutes and solvents, and molar volumes, values for can be estimated, or deviations from regularity can be assessed. These deviations can be estimated quantitatively and, in individual systems, can be ascribed to specific reactions in either of the phases, e.g., hydration, solvation, adduct formation, etc. 

In the preferential interaction model, the equilibrium association constant, K.ISVIC, for a peptide docked to a RPC sorbent can be related via eq 6 to the changes in the preferential interaction of the solvent and water with the peptide P- the ligands L, and the peptide-ligand complex PtL as a function of solvent concentration, [3]m. The effect of preferential hydration/solvation of a peptide on k can be represented in terms of the following expression t85l... 

Introducing a solute into a solvent initiates a toumciment of forces. Attractive forces between solute and solvent compete with attractive solute-solute and solvent-solvent forces. A solution forms only to the extent that solute-solvent forces dominate over the others. The process in which solvent molecules compete and win in the tournament of forces is called solvation or, in the specific case where water is the solvent, hydration. Solvated solutes are surrounded by solvent molecules. When solute ions or molecules become separated from one another and surrounded in this way, we say they re dissolved. 

What is the exact influence of water and organic molecules on the enzyme structure Could its effects on properties such as selectivity, affinity, binding constants, and catalytic constants be predictable by controlling the hydration/solvation state ... 

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. 

Impurities (including surfactants, hydrates, solvates, complexes, and reactive additives) can greatly inLuence the rate of dissolution by modifying the crystal habit or by interfering with the interfacial transport of solute from the crystal to the bulk solution. 

Determination of conditions under which API polymorphs, isomers, hydrates, solvates, and degradation products might form (also important for process patent reasons)... 

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

Smirnov, I.V. 2007. Anomalous effects in extraction of lanthanides and actinides with bidentate neutral organophosphorous extractants. Role of proton hydrate solvates. Radiochemistry 47(1) 44—54. 

In general, if an API form has stability problems in the bulk form, it is best to solve these issues via salt and form selection studies designed to discover and identify more thermodynamically stable forms prior to any excipient compatibility evaluation. It is known that different polymorphic forms and hydrated/solvated forms can have dramatically different stability profiles (23-26). 

Stability studies on the API include the evaluation of various forms of the active moiety, (e.g., different salts, hydrates, solvates, and polymorphs). After the API has been defined, stability studies are carried out as the... 

Solid-State Forms (Polymorphs, Hydrates, Solvates)... 

The AMI SCF-MO method was applied to calculate properties of all possible diazinodiazines and their monocations in order to get information about the site of protonation in these 7r-deficient heterocycles. Since some of these polyazanaphthalenes, like pteridine, are masked by the covalent hydration phenomenon the pA) values belong in fact to their hydrates, solvates, and mixtures of the adducts with the unmodified forms. Pteridine was found to be the strongest base in this series due to the high proton affinity at N-l <88JOC3900>. 

As maybe seen from Table 21.9, the computational quantum methods (both ab initio and DPT) agree well with each other and recent experiments of Froyd and Lovejoy [125]. Moreover, they were able to predict the abrupt drop in the enthalpy change at n = 4 related to the formation of the second hydration/solvation shell in good agreement with recent experiments [125]. 

Guillory, J. K. (1999). Generation of polymorphs, hydrates, solvates, and amorphous solids. In Physical characterization of pharmaceutical solids (ed. H. G. Brittain), pp. 183-226. Marcel Dekker, New York. [254]... 

What is the structure and the dynamics of hydrated/solvated electron in hot/supercritical water In dispersed clusters of polar liquids in nonpolar liquids In microheterogeneous media (e.g. water clusters in zeolite cavities) In mixed and complex solvents of practical importance (e.g. Ref. 107) on surfaces ... 

This still does not solve the problem if the molecules are known to be hydrated (solvated) mainly because the volume occupied by the hydrated (solvated) particle will obviously differ from that of the dry particle. Mathematically, consider the volume of the solution as a function of the concentrations of dry solute, m, and solvent, mo, the latter being the sum of the free solvent, mo, and bound solvent, mo. Thus... 

Thermal techniques (DSC, TGA) Determine melting point, heat capacity, heat of fusion Investigate polymorphic transitions Elucidate stability relationships between Polymorphs (monotropic vs enantiotropic) Detect the presence of hydrates/solvates Detect decomposition... 

In contrast to Ann, Ann 0 for all mixtures investigated, and hence, the polymers or proteins are preferentially hydrated (solvated in the case of toluene + polystyrene mixture). Let us examine separately the contributions to Ann provided by the entropic and enthalpic factors. The contribution to Ann provided by the different sizes of the solvent and polymer (protein) molecules will be evaluated from the excess in an ideal... 

Solid Form Selection A drug can exist in multiple forms in the solid state. If the two forms have the same molecular structure but different crystal packing, then they are polymorphs. Pseudopolymorphs (or solvatomorphs) differ in the level of hydration/solvation between forms. Polymorphs and pseudopolymorphs in principle will have a different solubility, melting point, dissolution rate, etc. While less thermodynamically stable, polymorphs have higher solubilities they also have the potential to convert to the more thermodynamically stable form. This form conversion can lead to reduced solubility for the formulated product. One example is ritonavir, a protease inhibitor compound used to treat acquired immune deficiency syndrome (AIDS). Marketed by Abbott Labs as Norvir, this compound began production in a semisolid form and an oral liquid form. In July 1998, dissolution tests of several new batches of the product failed. The problem was traced to the appearance of a previously unknown polymorph (Form II) of the compound. This form is thermodynamically more stable than Form I and therefore is less soluble. In this case, the solubility is at least a factor of 2 below that of Form I.12 The discovery of this new polymorph ultimately led to a temporary withdrawal of the solid form of Norvir from the market and a search for a new formulation. 

The equally critical issues of when to seed and how much seed to use are introduced in each classification. The amount of seed can vary from none to massive and include the familiar classifications of pinch to hopefully avoid complete nucleation, small (<1%) to hopefully achieve some growth, large (5-10%) to improve the probability of growth, and massive (the seed is the product in a continuous or semicontinuous operation) to provide maximum opportunity for all growth. The amount of seed can also be critical in the control of polymorphs and hydration/solvation. 

---