Pharmaceutical applications solvates

It was stated earlier that the vast majority of pharmaceutical solvates are hydrates. There are a few studies, however, in which other solvates of drugs have been studied. Ghosh et al. (27) examined a range of dialkylhydroxypyridones (iron chelators with possible application for the treatment of anemias) and compared their structures to their corresponding formic acid solvates. TGA was able to monitor the loss of formic acid, providing complementary information for spectroscopic studies that in turn were able to provide a molecular-level explanation for the desolvation profiles. 

QuantlogP, developed by Quantum Pharmaceuticals, uses another quantum-chemical model to calculate the solvation energy. As in COSMO-RS, the authors do not explicitly consider water molecules but use a continuum solvation model. However, while the COSMO-RS model simpUfies solvation to interaction of molecular surfaces, the new vector-field model of polar Uquids accounts for short-range (H-bond formation) and long-range dipole-dipole interactions of target and solute molecules [40]. The application of QuantlogP to calculate log P for over 900 molecules resulted in an RMSE of 0.7 and a correlation coefficient r of 0.94 [41]. 

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. 

Solvents are integral to our lifestyle today, contributing to the manufacture of numerous products such as pharmaceuticals, paints, inks, and microchips. They make it possible to process, apply, clean, or separate materials and are used across many industries (Fig. 3). Different applications require specific solvating or other properties, and solvents can be blended to achieve the properties necessary for a given application. 

Refs. [i] Marcus Y (1985) Ion solvation. Wiley, Chichester [ii] Marcus Y (1997) Ion properties. Marcel Dekker, New York [Hi] Osakai T, Ogata A, Ehina K (1997) J Phys Chem B 101 8341 [iv] Osakai T, Ebina K (2001) Ion solvation and resolvation. In Volkov AG (ed) Liquid interfaces in chemical, biological, and pharmaceutical applications. Marcel Dekker, New York, p 23... 

TG can be used with different atmospheres and under vacuum. TG has a huge number of pharmaceutical applications. Automated TG is extremely efficient to replace the loss on drying assay in drug substances, being able to separate loss of solvent from decomposition by using very small amounts of substance. Solvent entrapped or bounded as solvate is easily determined. A comprehensive article on TG has been recently written by Dunn and Sharp. Ozawa proposes the use of modulated TG for kinetic analysis. ... 

Selecting and producing the solid phase of this compound for pharmaceutical applications indicates how complex these situations can become. The organic solvates, in general, are ruled out based... 

The mechanism of dissolution was proposed by Nernst (1904) using a film-model theory. Under the influence of non-reactive chemical forces, a solid particle immersed in a liquid experiences two consecutive processes. The first of these is solvation of the solid at the solid-liquid interface, which causes the formation of a thin stagnant layer of saturated solution around the particle. The second step in the dissolution process consists of diffusion of dissolved molecules from this boundary layer into the bulk fluid. In principle, one may control the dissolution through manipulation of the saturated solution at the surface. For example, one might generate a thin layer of saturated solution at the solid surface by a surface reaction with a high energy barrier (Mooney et al., 1981), but this application is not commonly employed in pharmaceutical applications. 

The technique of x-ray diffraction is exceedingly important to pharmaceutics because it represents the primary method for obtaining fundamental structural information on crystalline substances. For example, it is only by pure coincidence that two compounds form crystals in which the three-dimensional spacing of planes is identical in all directions. One such example is provided by the trihydrate phases of ampicillin and amoxicillin, but such instances are uncommon. Typical applications of x-ray diffraction methodology include the determination of crystal structures, evaluation of polymorphism and solvate structures, evaluation of degrees of crystallinity, and the study of phase transitions. 

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