Solubility theory

It may be possible to predict the permeation characteristics of the fluorinated layer by using the acid-base theory of surface energy together with solubility theory.38... 

In the previous section, the optimisation of liquid-liquid extraction with the help of mixture designs justified by the solubility theory was examined. A relation was derived between the partition coefficient and the mixture composition for liquid-liquid extraction with extraction liquids composed of three components, and a special cubic mixture model was obtained (equation (3)). 

The effects of various factors such as pH, the common ion effect, and temperature on solubility will have a greater impact on formulation development for insoluble compounds than for soluble ones. The general solubility theory has been extensively discussed in the literature (James, 1986 Grant and Higuchi, 1990). To afford better understanding of the solubility behavior of insoluble compounds, the pertinent solubility theory and its practical implications will be reviewed here. 

Other attempts at characterizing the deviation from ideal solubility theory have been made. Anderson et al. [50] showed that solubilities that could not be rationalized from the regular solution theory could be rationalized by assuming the formation of speciLc solute-solvent complexes. Yalkowsky et al. [51,52] showed that the deviation from the ideal solubility equation could be expressed in terms of interfacial tension and surface area. In equation form,... 

Based on the above types of information and solubility theory for nonelectrolytes as given in Hildebrand and Scott (6), a new way of describing... 

To quantify the concepts given above, it is necessary to devise a polarity scale related to solubility theory. Since the precipitating solvents for asphaltene separation are at the low end of the solubility parameter scale, it seems... 

Solubility theory based on pH-solubility profiles for weak acids and bases is well established (Grant and Higuchi, 1990, Butler, 1998). From a knowledge of the intrinsic solubility of the unionized form, the dissociation constant (plC. ) and the solubility of a salt, one should be able to construct the pH-solubility profile. If multiple solubility data are available, data can be analyzed through the use of a non-linear regression model to calculate plC, . If the solubilities of the various salts are also determined, the complete pH-solubility profile can be constructed. 

Deviations from the theoretical pH-solubility profiles may be an indication of experimental error. They may also suggest other interactions not predicted by the solubility theory. Examples for the causes of such deviations include changes in solid-state properties, self-association and micelle formation of the drug in solution. Figure 1 shows an example of a compound that forms micelles at a pH above 9 (Winnike, 2005). Further addition of sodium hydroxide does not increase the pH rather it enhances solubility through micelle formation. In any of these cases, it is important to identify the causes of the deviation so that appropriate formulation decisions can be made based on the solubility data. 

Fortunately, most organic solvents are nonpolar and therefore their intermolecular forces are weak London or dispersion forces. Hildebrand used the term "regular solutions" to describe solutions of nonelectrolytes and their nonpolar solvents. Additional theories on the solubility of polymers were developed by Flory ( ) and Huggins O). Probably the most important publications leading to the practical use of solubility theories by polymer scientists were those published by Burrell in 1955 ( ) and 1966 ( ). Modifications in the Hildebrand solubility parameter concept for regular solutions to account for larger intermolecular forces were made by Liebermann ( ), Crowley (.7), Hansen and Beerbower ( ) and Nelson et al. (9). 

Before we begin the discussion of specific sample preparation techniques, it is necessary to review some of the fundamental theories that control these separation techniques (see Table 4). Phase equilibrium theories, phase contact, and countercurrent distributions provide the basis for the extraction techniques, e.g., liquid-liquid extractions as well as the various solid-phase extraction techniques. Solubility theories provide the basis for the preparation and dissolution of solid samples. Finally, understanding of the basic physicochemical theories that control intermolecular interactions is critical for successful development of sample preparation methods. 

During the inhalation of silica dust, silica particles are hydrated. The degree of silica solubility is directly proportional to its final toxicity. Particles smaller than 2 to 3 pm are assumed to be more soluble than larger particles. This solubility theory assumes a release of silicic acid, which may be combined with tissue components, thus increasing collagen production... 

Miscibility between the individual polymers is the most important factor to determine the performance characteristics of a polymer blend. Mutual solubility of the phases, the thickness and properties of the interphase formed during blending and the structure of the blend are mainly dependent on the miscibility of individual polymers within a polymer. As a result, a quantitative estimation of interactions is very much important for the prediction of blend properties. Comparison of solubility parameters of individual polymers is an effective method to predict the extent of miscibility within a blend. According to the Hildebrand solubility theory, a large difference in solubility parameters (6p) of individual matrices results in immiscibility between them in the absence of any interfacial compatibil-izer [222]. Jandas et al. have reported that PLA and PHB have Hildebrand solubility parameters (6p) of 23.5 J /cm and 19.8 J Vcm which can turn out to be partially miscibile blends in between them [35]. In case of partially miscible blends, the miscibility can be controlled by compatibili-zation using proper interactables. 

Sung and Lazar [173], and Birks [82] depend on a parabolic rather than a linear fit of the data (as mentioned in Section 3.2) and may still apply for restricted systems indeed, some such limitation applies to theories on most aspects of carcinogenesis. Thus Cammerata, Yau and Rogers [175] presented relations between ionization potentials—molecular polarizabilities and partition coefficients. The inference of a link between solubility theories and MO indices is not unexpected in view of the influence of molecular polarizability on dispersion-attraction interaction energies in solution. An approximate, though rather less relevant, inverse dependence of ionization potential on polarizability has been noted [176]. 

Another useful tool is the Hildebrand solubility theory, which is applicable to apolar and moderately polar systems. For strongly polar systems, it is unable to correctly qualify the compatibility between components. However, the massive amount of interaction parameters data obtained in recent decades, and mainly Small s method, allowing to assess them, make this method quite efficient and readily applicable. The Hildebrand solubility parameter, 5, can be defined as the square root of the cohesive energy density (CED) and it is measured in (MJ m )° . This parameter indicates the polarity level of the component and goes from 12 (MJ m )° for nonpolar components to 23 (MJ m )° for water. The larger the difference... 

Silicosis-Pncumoconiosis-Fibrinogencsis Mechanism of silicosis, Amorphous versus crystalline silica and particle size. Susceptibility to silicosis. An unusual compound in silico tic tissues, Solubility theory. Silica antagonists to prevent silicosis Asbestosis-Microaciculosis BeneFicial Effects of Silica Silicon Metabolism Silica Gel as a Culture Medium Organosilicon Compounds Analytical Problems Conclusion References... 

He concluded that the solubility theory was not applicable. Instead the chemical properties of the surface of the silica particle directly involved them in reaction with tissues. Physical theories were generally judged inadequate. Although there may be some correlation between specific surface area, or adsorption, capacity for albumin and pathogenicity, exceptions can generally be found. An explanation of how a silica particle kills a phagocyte is far from an explanation of the biochemical interactions involved in the development of a silicotic lesion. 

Stdber surveyed the history of silicosis and the three main theories involving (1) solubility of silica, (2) surface interactions of silica, and (3) immune reactions resulting from the presence of silica. He then presented a summary of extensive tests made with particles of all known forms of silica in which surface properties and dissolution characteristics were correlated with their biological reactions (309). He pointed out that the simple solubility theory cannot be correct. The fact is that if one arranges the various forms of silica in order of increasing solubility (crystalline silicas, opal, fine-particle amorphous silica, and colloidal silica) the fibrogenic activity decreases whereas the toxicity to tissues increases. 

Heppleston (310, 311) in 1972 reviewed the main theories of the Hbrogenic action of silica likewise classified as (1) solubility, (2) surface, and (3) immunological. The immunological theory is of secondary importance because it does not explain the primary action of silica in stimulating proliferation of connective tissue, llie solubility theory was left by default, but was still inadequate because neither the known surface structures of the different modifications of silica nor their characteristic adsorption of albumin or gamma globulin could be correlated with their relative biological activity. However Stober (312) showed that all crystalline forms except stishovite are relatively active. 

It now appears that the solubility theory cannot account for the development of typical silicosis which involves Fibrosis. However, polysilicic acids and colloidal silicas certainly have other toxic effects in tissues and on living cells. Much of the work originally directed toward silicosis and based on the solubility theory failed to explain the mechanism of Fibrosis and silicosis but nevertheless provided much of what we now know about the other effects of silica. ... 

Another way to account for the formation of polysilidc acid and colloidal silica from quartz particles is that the particles contain an unusually soluble fraction when freshly formed. Accordingly, Holt proposed an extended solubility theory, which postulated that silica dust particles can initially produce a supersaturated solution of silica which then polymerizes. Both Holt (331) and Soffge (306) emphasized the dissolution of silica followed by polymerization. The silica particles are collected and concentrated by phagocytes, creating higher local concentrations. Collagen is adsorbed and cross-linked by the silicic acid in a manner similar to silica tanning. 

An objection to Holt s extended solubility theory was that it gave no explanation as to why particles of submicron quartz were more toxic than particles of the more soluble types of silica. However, Jager pointed out that the disturbed layer on the surface of quartz was unusually soluble and proposed that it furnished... 

Other apparent support for the solubility theory by silicosis came from several sources. The less soluble types of silica were less harmful. Thus the deposition of soluble aluminum ions on the silica surface reduces solubility as well as toxicity (337-340). Also, aluminosilicate minerals such as clays, which are even less soluble than quartz, do not cause silicosis. The report that silicotic lung tissues contained esters of silicic acid, for example, cholesterol (341), seemed also to support the idea that soluble silica must be involved. 

The solubility theory was not wrong, in that it was based on many valid observations and explained many of the cytotoxic and other harmful effects that can occur in the animal system when silica is introduced by unnatural means. However, there was a false but persistent belief that these effects must result in the fibrosis that is characteristic of silicosis. 

Effect of Alumina in Silicosis. As mentioned in connection with the solubility theory or silicosis, Haldane (337) early in this century recognized that alumina had an antagonistic or preventive effect on the development of silicosis. While the solubility theory was in vogue, this seemed to be logical since it was known that when alumina was mixed with silica, much less soluble silica appeared in solution. Now the surface" theory requires a further explantion. 

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