Solubility coefficient, influence

Lipophilicity is determined by measuring the equilibrium solubility of a compound in a lipophilic phase such as octanol to its solubility in an aqueous phase such as water. Analytical measurements relate pKa to log P (the partition coefficient). Log P is a physicochemical parameter of aqueous and lipid solubility that influences the delivery of drugs to their target when the drug is in the neutral state. 

In contrast to the LCP results just presented, in glassy polymers used as gas separation membranes, free volume influences diffusion coefficients much more than solubility coefficients. Figure 6 provides an example of this effect. In this figure, the solubility, diffusivity, and permeability of methane in a series of glassy, aromatic, amorphous poly(isophthalamides) [PIPAs] are presented as a function of the fractional free volume in the polymer matrix. (More complete descriptions of the transport properties of this family of materials are available elsewhere (59, 40)). The fractional free volume is manipulated systematically in this family of glassy polymers by synthesizing polymers with different substituent and backbone elements as shown in... 

Several factors influence the effective value of diffusion and solubility coefficients, and thus barrier properties, in polymers ... 

Permeability. Many polymers are used in packaging and, in particular, for food. In this latter case the permeability to gases and vapors is of prime importance. The permeation or transmission of a gas or vapor is a function of the solubility of a gas or vapor in the polymer and the rate of diffusion through the matrix. The permeability coefficient, diffusion constant, and solubility coefficients can all be measured and are influenced by the chemical structure and morphology. In order to achieve the required permeability characteristics it is common to co-extrude a series of polymers to form a laminated structure. Such materials allow selective permeation of a specific species and enhance the life of the product (190,191) (see Transport Properties). 

The solubility coefficient 5 of a permeant can mainly be influenced by varying the functional groups and thus changing the polarity of the hybrid polymer. The inorganic network density as well as the organic network density are important factors, in particular for the diffusion coefficient of the permeants (see Fig. 21-10). 

Steady-state permeability is defined as the flux of penetrant per unit pressure difference across a sample of unit thickness. Permeation through polymers is generally a three step process absorption of penetrant into the polymer matrix, diffusion of penetrant through the matrix and desorption of penetrant at the other side (Kirwan and Strawbridge, 2003). Thus, permeability is influenced both by the dissolution and the diffusion of the penetrant in the polymer matrix. In this sorption-diffusion model of penetrant transport across the polymer, permeability (P) is given as the product of diffusion coefficient () and solubility coefficient () (Callister and Rethwisch, 2010), that is ... 

Barrier properties of materials indicate their resistance to diffusion and sorption of molecules. A good barrier polymer has low values of both diffusion (D) and solubUity (S) coefficients. Since the permeabUity coefficient P is a derived function of D and S, a high-barrier polymer has low values of P. The diffusion coefficient is a measure of how fast a penetrant will move within the polymer in a particular direction, while the solubility coefficient gives the amount of the penetrant taken (or sorbed) per unit mass of polymer from a contacting phase per unit of sorbate concentration. Both diffusion and solubility can be applied to the reverse process of sorption, that is, the migration of compounds from the polymer to a surrounding media. Several factors influence the effective value of diffusion and solubility coefficients in polymers. 

Thirdly, the adhesive type does appear to influence the environmental stability of the interfacial regions. For example, especially noteworthy is the often-superior joint durability shown, in the case of bonding aluminium alloys, by some of the older phenolic-based structural adhesives, compared to the more modern epoxy-based adhesives. This does not arise from the phenolics possessing lower diffusion or solubility coefficients with respect to water than the epoxies [153]. Indeed, many such phenolic adhesives are more permeable to moisture. However, it may arise from the ability of the phenolics to establish stronger, more stable intrinsic interfacial forces, as discussed later. Alternatively, it may arise from the pH of residues from phenolic-based adhesives being acid and therefore not attacking and weakening the aluminium oxide, unlike the more alkaline extracts from some of the epoxies. It is believed... 

Because the solubility coefficients of carbon in the solid and the liquid phase are almost the same, zone melting, which is used to prepare high-purity crystals of many other elements, is not suitable in the case of boron. Technical boron, which is often taken as the ingredient for the preparation of boron compounds, contains up to about 0.5% carbon. However, in several preparative methods for boron compounds the carbon content may be reduced by secondary chemical or physical reactions. The purest P-rhombohedral boron crystals that have become available up to now were produced by Wacker-Chemie, Munich, FRG. Despite the claimed purity of 99.9999% with respect to other elements, even this high-purity boron contains carbon in concentrations of typically 30 to 80 ppm. Therefore, apart from boron carbide containing carbon as a determining bonding partner, in the assessment of the properties of boron and boron compounds attention must be paid to the fact that a certain, usually unknown carbon content could have influenced the properties determined. 

The horizontal portion of the plot in Figure 23.6 represents the equilibrium mass uptake—the amount absorbed at equilibrium whose magnitude is influenced by the solubility parameter 8 (Section 23.4.3.1). In reality, coefficient D quite often varies with concentration, so that the overall plot takes on a sigmoid shape (see Section 23.4.4.3), although a horizontal portion is still usually achieved eventually if it is not, the elastomer is possibly a two-phase material (a blend), with one phase much slower at absorbing the incoming liquid. 

There are several factors through which anions can influence the pathway and O2 reduction kinetics. The main factors are competition with O2 for surface sites changes in the activity coefficients of the reactants, intermediates, and transition states and the acidity and dielectric properties of the electrolyte side of the interface [Adzic, 1998]. For example, perfluoro acids have higher O2 solubility and lower adsorbability than... 

Another perspective provided by this model is the effect of three physiochemical parameters—solubility, distribution coefficient, and molecular mass—on transcoreal flux. All of these properties can be influenced by molecular design. The effects of these properties are illustrated in Fig. 13, in which the logarithm of the flux is plotted as a function of solubility and distribution coefficient for two different Mr. Several features of the model are depicted, and these qualitative, or semi-quantitative, aspects presumably encompass the principles of corneal permeation. 

Fig. 14 Plot of data in Table 2 the theoretically computed permeability coefficient versus that measured. The larger influence on flux is often the range of solubility, which can increase the range in flux by several orders of magnitude.

Table 5 shows that the ratio of the excretion rate under hydrous condition to that under anhydrous condition decreases with the decreasing water solubility of the salicylate or with the oil/water distribution coefficient. It can be said that the more water soluble compound is aided to a greater degree by the presence of moisture than those of lesser solubility. This trend is, however, not a direct proportionality due to the influence of other physical phenomena such as viscosity, molecular size, and intermolecular bonding. 

To summarize, the hydration status of the drug molecule and other components of a pharmaceutical formulation can affect mass transport. Solubility of drug crystals in an aqueous or nonaqueous solvent may depend on the presence or absence of moisture associated with the drug. Hydration may also determine the hydrodynamic radii of molecules. This may affect the frictional resistance and therefore the diffusion coefficient of the drug molecules. Diffusion of drugs in polymeric systems may also be influenced by the percent hydration of the polymers. This is especially tme for hydrogel polymers. Finally, hydration of... 

Several attempts have been made to estimate the dose required in humans in relation to a drug s potency, and to put this into the context of solubility and permeability for an optimal oral drug [2, 3]. A relatively simple example of this is where a 1.0 mg kg-1 dose is required in humans, then 52 pg mL"1 solubility is needed if the permeability is intermediate (20-80%) [3]. This solubility corresponds approximately to 100 pM of a compound with a MW of 400 g mol-1. Most screening activities for permeability determinations in, e.g., Caco-2, are made at a concentration of 10 pM or lower due to solubility restrictions. The first implication of this is that the required potency for these compounds needs to correspond to a dose of <0.1 mg kg-1 in humans if the drug should be considered orally active. Another implication would be the influence of carrier-mediated transport (uptake or efflux), which is more evident at low concentrations. This could result in low permeability coefficients for compounds interacting with efflux transporters at the intestinal membrane and which could either be saturated or of no clinical relevance at higher concentrations or doses. 

Heterogeneous conditions both in terms of hydrodynamics and composition prevails in the GI tract. Parameters such as D, Cs, V, and h are influenced by the conditions in the GI tract which change with time. Thus, time dependent rate coefficients govern the dissolution process under in vivo conditions. One of the major sources of variability for poorly soluble drugs can be associated with the time dependent character of the rate coefficient, which governs drug dissolution under in vivo conditions. 

Phthalocyanine-based dyes are especially useful for CD-R, as the chromophore absorption band falls in the desirable spectral range, and they are noted for excellent photostability. Unlike cyanine dyes, phthalocyanines tend to have very poor solubility, particularly in solvents such as alcohols and aliphatic hydrocarbons (which do not attack polycarbonate and are therefore used for spin coating). Therefore, the main barrier to the wider use of these dyes is the relatively high cost of synthesizing soluble derivatives. Suitable modifications to the Pc core which have been developed, notably by Mitsui Toatsu, are shown in Scheme 7. The bulky R groups reduce undesirable molecular association (which in turn lower the extinction coefficient and hence reflectivity), whereas partial bromination allows fine-tuning of the film absorbance and reflectivity. The metal atom influences the position of the absorption band, the photostability, and the efficiency of the radiationless transition from the excited state.199 This material is marketed by Ciba as Supergreen.204... 

If the molecular species of the solute present in solution is the same as those present in the crystals (as would be the case for nonelectrolytes), then to a first approximation, the solubility of each enantiomer in a conglomerate is unaffected by the presence of the other enantiomer. If the solutions are not dilute, however, the presence of one enantiomer will influence the activity coefficient of the other and thereby affect its solubility to some extent. Thus, the solubility of a racemic conglomerate is equal to twice that of the individual enantiomer. This relation is known as Meyerhoffer s double solubility rule [147]. If the solubilities are expressed as mole fractions, then the solubility curves are straight lines, parallel to sides SD and SL of the triangle in Fig. 24. 

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