Apparent solubilities

Changes in the pH of subsurface aqueous solutions may lead to an apparent increase or decrease in the solubility of organic contaminants. The pH effect depends on the structure of the contaminant. If the contaminant is sensitive to acid-base reactions, then pH is the governing factor in defining the aqueous solubility. The ionized form of a contaminant has a much higher solubility than the neutral form. However, the apparent solubility comprises both the ionized and the neutral forms, even though the intrinsic solubility of the neutral form is not affected. 

As mentioned previously, the physical state of a solute is susceptible to modifications by interaction with cosolvents. In principle, a cosolvent can enhance solute solubility by changing the solvency of the medium, by direct solute interaction, by adsorption, or by partitioning (Chiou et al. 1986). In a batch experiment testing the effect of humic acid on kerosene dissolution in an aqueous solution, Dror et al. (2000a) found a linear correlation between the amount of humic acid and the amount of kerosene that dissolved (Fig. 6.5). 

The enhancement of kerosene dissolution occurs even at low humic acid content in the aqueous solution. In view of the fact that humic substances are relatively high molecular weight species containing nonpolar organic moieties, Chiou et al. (1986) assumed that a partition-like interaction between a solute of very low solubility in aqueous solution and a microscopic organic environment of dissolved humic molecules can explain solute solubility enhancement. 

When a NAPL reaches the subsurface, it may by subject to mechanical forces that lead to the formation of a mixed NAPL-water micro-/nanoemulsion characterized by the presence of micro- and nanodroplets of organic compounds. These micro- and nanoemulsions are transparent or translucent systems, kinetically (nano-) or thermodynamically (micro-) stable, and display an apparent increase in aqueous solubility as compared to the intrinsic solubility of the NAPL itself (Tadros 2004). The very small droplet size (50-200 nm in the case of a nanoemulsion) causes a large reduction in the force of gravity, enabling the system to remain dispersed and 

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Sorption curves obtained at activity and temperature conditions which have been experienced to be not able to alter the polymer morphology during the test, i.e. a = 0.60 and T = 75 °C, for as cast (A) and for samples previously equilibrated in more severe conditions, a = 0.99 and T = 75 °C (B), are shown in Fig. 13. According to the previous discussion, the diffusion coefficient, calculated by using the time at the intersection points between the initial linear behaviour and the equilibrium asymptote (a and b), for the damaged sample is lower than that of the undamaged one, since b > a. The morphological modification which increases the apparent solubility lowers, in fact, the effective diffusion coefficient. 

Van Bloois, L., Dekker, D. D., and Crommelin, D. J. A. (1987). Solubilization of lipophilic drugs by amphiphiles Improvement of the apparent solubility of almitrine bismesylate by liposomes, mixed micelles and O/W emulsions, Acta Pharmaceut. TechnoL,... 

The results of a pH 4-9.5 solubility assay of chlorpromazine are shown in Fig. 6.10. The horizontal line represents the upper limit of measurable solubility (e.g., 125 pg/mL), which can be set by the instrument according to the requirements of the assay. When the measured concentration reaches the line, the sample is completely dissolved, and solubility cannot be determined. This is automatically determined by the instrument, based on the calculated value of R. When measured points fall below the line, the concentration corresponds to the apparent solubility Sapp. 

Figure 6.12 Correction of the apparent solubility pH profile (solid curves) for the effect of DMSO and/or aggregation (a) chlorpromazine (b) terfenadine (c) piroxicam (d) phen-azopyridine. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Using such dielectric-based predictions, when the methanol-apparent solubility, log Sq versus wt% methanol is extrapolated to 0% cosolvent, the aqueous solubility, log So, can be estimated when log S(0 is extrapolated to 100% cosolvent, the membrane solubility, log iS cm, can be estimated. The approximate membrane partition... 

This chapter describes some of the properties of solids that affect transport across phases and membranes, with an emphasis on biological membranes. Four aspects are addressed. They include a comparison of crystalline and amorphous forms of the drug, transitions between phases, polymorphism, and hydration. With respect to transport, the major effect of each of these properties is on the apparent solubility, which then affects dissolution and consequently transport. There is often an opposite effect on the stability of the material. Generally, highly crystalline substances are more stable but have lower free energy, solubility, and dissolution characteristics than less crystalline substances. In some situations, this lower solubility and consequent dissolution rate will result in reduced bioavailability. 

The extent of hydration or solvation of a molecule also has a profound effect on the transport of the substance. The apparent solubility of the drug in both aqueous and nonaqueous media may be influenced by the absence or presence of moisture. Diffusion of drugs in polymeric systems may also be influenced by the hydration of the polymers and hydration of the membrane through which transport is occurring for example, skin hydration may enhance the diffusion of drug molecules significantly. 

Thus, any factor that affects the solubility or apparent solubility of a drug entity has the potential of affecting the dissolution and diffusion mass transport of the molecule as shown in Eq. (6) [or Eq. (1)]. Polymorphism is one such important... 

A polymorph is a solid crystalline phase of a compound resulting from the possibility of at least two different crystal lattice arrangements of that compound in the solid state [42], Polymorphs of a compound are, however, identical in the liquid and vapor states. They usually melt at different temperatures but give melts of identical composition. Two polymorphs of a compound may be as different in structure and properties as crystals of two different compounds [43,44], Apparent solubility, melting point, density, hardness, crystal shape, optical and electrical properties, vapor pressure, etc. may all vary with the polymorphic form. The polymorphs that are produced depend upon factors such as storage temperature, recrystallization solvent, and rate of cooling. Table 2 suggests the importance of polymorphism in the field of pharmaceutics [45],... 

At a certain temperature of transition Tt, the two forms will be in equilibrium, AG will be zero, and m = m2. But at other temperatures the two forms will not be in equilibrium, and if ax > a2 then because AG = Z rin (a2/fli), AG will be negative and polymorph 1 will change spontaneously to polymorph 2 and will therefore be considered the less stable form and vice versa. Studies of the two polymorphic forms of methylprednisolone show that significant differences occur in the apparent solubilities of polymorphic forms and that these may be temperature-related. 

Hydration can be an important factor in diffusion and mass transport phenomena in pharmaceutical systems. It may alter the apparent solubility or dissolution rate of the drug, the hydrodynamic radii of permeants, the physicochemical state of the polymeric membrane through which the permeant is moving, or the skin permeability characteristics in transdermal applications. 

Adding compounds solubilized in DMSO to aqueous medium as part of a discovery solubility assay can lead to two types of solubility assay with different uses. At one extreme, the quantity of DMSO is kept very low (<1%). At this low level of DMSO, the solubility is only slightly affected by the DMSO content. For example, data from a poster by Ricerca Ltd. [11] suggest that a DMSO content of 1% should not elevate apparent solubility by more than about 65%. At 5% DMSO, this group reported an average solubility increase of 145% due to the DMSO content. Solubility in an early discovery assay containing one percent DMSO can however exceed thermodynamic solubility by much more than 65%. However, this is very likely due to the time scale. Studies by the Avdeef (plon Inc.) group show a close approximation of early discovery solubility (quantitated by UV) to literature ther-... 

The calculation is illustrated in Table 1.5.5 for pentachlorophenol. The experimental aqueous solubility is 14.0 g/m3 at a pH of 5.1. The environmental pH is 7. Higher environmental pH increases the extent of dissociation, thus increasing the Z value in water, increasing the apparent solubility, decreasing the apparent KqW and Henry s law constant and the air-water partition coefficient, and decreasing the soil-water partition coefficient. 

Most acid dissociation constants pKa exceed environmental pH values, the exceptions being the highly chlorinated phenols. As a result, these substances tend to have higher apparent solubilities in water because of dissociation. The structure-property relationships apply to the un-ionized or protonated species thus, experimental data should preferably be corrected to eliminate the effect of ionization, thus eliminating pH effects. 

Certain compounds are known to achieve higher absorption rates from the GI tract if they are taken with food, and this observation has been linked to their solubilization by bile salts [74], Bile salts, especially those of cholic and deoxycholic acids, have been used to solubilize steroid hormones [75], antibiotics [76], and nonsteroidal antiinflammatory drugs [77]. For example, amphotericin B (an antifungal agent) has been solubilized for parenteral use in micelles composed of sodium desoxycholate [78], As illustrated in Fig. 11, the degree of solubilization of carbamazepine by sodium desoxycholate is minimal below the critical micelle concentration but increases rapidly above this value [79]. At sufficiently high concentrations, when the micelles become saturated in carb-amezepine, the apparent solubility reaches a limiting value approximately seven times the true aqueous solubility in the absence of desoxycholate. 

Colloids are suspended particles in a solution medium and will not settle out over time. They are common in natural waters and can enhance the apparent solubility of a wide range of water pollutants, both organic and inorganic. Colloids maybe considered as an extension of the solid and aqueous phases and are formed by conditions that can be quite variable in time and space hence colloids can be dynamic. The composition of colloids can vary with the composition of the solid and aqueous phases. Colloids can be made up of organic, inorganic, or a mixture of materials. 

Colloids have repeatedly been shown to be important in enhancing the apparent solubility of hydrophobic organic chemicals [4, 19, 62, 96, 105, 106, 111-113]. The solid phase is the source of dissolved or suspended colloidal material which acts as the third phase. It is observed that the solution phase is in dynamic equilibrium with the solid phase. 

The presence of water-soluble macromolecules in solution at submicel-lar concentrations has been reported to enhance the water solubility of hydro-phobic organic chemicals in several instances [19, 106, 113]. The presence of macromolecules in solution can enhance the apparent solubility of solutes by sorptive interactions in the solution phase. The processes by which macromolecules enhance the solubility of pollutants are probably variable as a function of the particular physical and chemical properties of the system. A macromolecule possessing a substantial nonpolar region can sorb a hydrophobic molecule, thereby minimizing the interfacial tension between the solute and the water. 

It has also been shown [254] that a commercial petroleum sulfonate surfactant which consists of a diverse admixture of monomers does not exhibit behavior typically associated with micelle formation (i.e., a sharp inflection of solvent properties as the concentration of surfactant reaches CMC). These surfactants exhibit gradual change in solvent behavior with added surfactant. This gradual solubility enhancement indicates that micelle formation is a gradual process instead of a single event (i. e., CMC does not exist as a unique point, rather it is a continuous function of molecular properties). This type of surfactant can represent humic material in water, and may indicate that DHS form molecular aggregates in solution, which comprise an important third phase in the aqueous environment. This phase can affect an increase in the apparent solubility of very hydrophobic chemicals. 

Application of pollutant chemodynamic models, which neglect the DHS phase, may result in inaccurate estimations of apparent solubility and transport parameters. The impact of a DHS solubility enhancement is most pronounced for the least water-soluble solutes. The affinity of a solute for a DHS is a function of the same properties, which drive a complex organic mixture(s) to sorb onto the stationary solid phase, namely bonding interactions and hydrophobicity. 

Partitioning of PCBs into other organic compound mixtures or phases found in the environment alters environmental parameters used to estimate their fate and transport. For example, dissolved phase humic substances (i.e., DPUS) can increase the apparent solubility of organic pollutants [381-390] (see Chap. 2). 

Evaluating the effect of hydroxypropyl cyclodextrine (HPCD) on phenan-threne solubilization and biodegradation, showing HPCD significantly increased the apparent solubility (i.e., the bio availability) of phenanthrene, having a major impact on the biodegradation rate of phenanthrene [193]. 

Biggar, J.W. and Riggs, I.R. Apparent solubility of organochlorine insecticides in water at various temperatures, Hilgardia, 42(10) 383-391, 1974. 

One way that contaminants are retained in the subsurface is in the form of a dissolved fraction in the subsurface aqueous solution. As described in Chapter 1, the subsurface aqueous phase includes retained water, near the solid surface, and free water. If the retained water has an apparently static character, the subsurface free water is in a continuous feedback system with any incoming source of water. The amount and composition of incoming water are controlled by natural or human-induced factors. Contaminants may reach the subsurface liquid phase directly from a polluted gaseous phase, from point and nonpoint contamination sources on the land surface, from already polluted groundwater, or from the release of toxic compounds adsorbed on suspended particles. Moreover, disposal of an aqueous liquid that contains an amount of contaminant greater than its solubility in water may lead to the formation of a type of emulsion containing very small droplets. Under such conditions, one must deal with apparent solubility, which is greater than handbook contaminant solubility values. 

A combined effect of natural organic matter and surfactants on the apparent solubility of polycyclic aromatic hydrocarbons (PAHs) is reported in the paper of Cho et al. (2002). Kinetic studies were conducted to compare solubilization of hydro-phobic contaminants such as naphthalene, phenanthrene, and pyrene into distilled water and aqueous solutions containing natural organic matter (NOM) and sodium dodecyl sulfate (SDS) surfactant. The results obtained after 72hr equilibration are reproduced in Fig. 8.19. The apparent solubility of the three contaminants was higher in SDS and NOM solutions than the solubility of these compounds in distilled water. When a combined SDS-NOM aqueous solution was used, the apparent solubility of naphthalene, phenanthrene, and pyrene was lower than in the NOM-aqueous solution. 

Zhong et al. (2003) studied the apparent solubility of trichloroethylene in aqueous solutions, where the experimental variables were surfactant type and cosolvent concentration. The surfactants used in the experiment were sodium dihexyl sulfo-succinte (MA-80), sodium dodecyl sulfate (SDS), polyoxyethylene 20 (POE 20), sorbitan monooleate (Tween 80), and a mixture of Surfonic- PE2597 and Witconol-NPIOO. Isopropanol was used as the alcohol cosolvent. Eigure 8.20 shows the results of a batch experiment studying the effects of type and concentration of surfactant on solubilization of trichloroethylene in aqueous solutions. A correlation between surfactant chain length and solubilization rate may explain this behavior. However, the solubilization rate constants decrease with surfactant concentration. Addition of the cosolvent isopropanol to MA-80 increased the solubility of isopropanol at each surfactant concentration but did not demonstrate any particular trend in solubilization rate of isopropanol for the other surfactants tested. In the case of anionic surfactants (MA-80 and SDS), the solubility and solubilization rate increase with increasing electrolyte concentration for all surfactant concentrations. 

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