Solubility value

The group contribution method allows the approximate calculation of solubility by summing up fragmental values associated with substmctural units of the compounds (see Section 7.1). In a group contribution model, the aqueous solubility values are computed by Eq. (12), where log S is the logarithm of solubility, C is the number of occurrences of a substmctural group, i, in a molecule, and is the relative contribution of the fragment i. 

Figure 10.1-3. Predicted versus experimental solubility values of 552 compounds in the test set by a back-propagation neural network with 18 topological descriptors.

Selection of Solubility Data Solubility values determine the liquid rate necessaiy for complete or economic solute recoveiy and so are essential to design. Equihbrium data generally will be found in one of three forms (1) solubility data expressed either as solubility in weight or mole percent or as Heniy s-law coefficients, (2) pure-component vapor pressures, or (3) equilibrium distribution coefficients (iC values). Data for specific systems may be found in Sec. 2 additional references to sources of data are presented in this section. 

The reverse of Example 16.4 involves finding Rq, of a compound given its solubility. The solubilities of many ionic compounds are determined experimentally and tabulated in chemical handbooks. Most solubility values are given in grams of solute dissolved in 100 grams of water. To obtain the molar solubility in moles/L, we have to assume that the density of the solution is equal to that of water. Then the number of grams of solute per 100 g water is equal to the number of grams of solute per 100 mL of solution. This assumption is valid because the mass of the compound in solution is small. To solve for IQp, find the molar solubility of the solute and determine the concentration of its component ions. Substitute into the IQp expression. 

The binding constants of a number of compounds were measured using dialysis, solubility and sorption techniques. The solubility technique was used for compounds which were not radiolabeled. All data was collected at pH = 8.3. The binding constants were then compared to the octanol/water partition coefficients for the compounds and the molar solubilities of the compounds. The data is presented in Table II. The Kow values were taken from the literature.18 22-2 The solubility values were determined in this research with the exception of DDT and Lindane, which were taken from the literature. A plot of log Kc vs. log Kow is presented in Figure 5. The slope of this line is 0.71, the intercept is 0.75 and the value of the correlation coefficient is 0.9258. The regression is highly significant... 

Oxidative bleaching of wool is invariably carried out with hydrogen peroxide. The active species involved is likely to be the same as on cellulosic substrates but specific reactions with wool amino acid residues must be considered. The primary reaction is oxidation of cystine disulphide bonds leading to the formation of cysteic acid residues (Scheme 10.41). The rupture of disulphide crosslinks, with attendant increase in urea-bisulphite and alkali solubility values, adversely affects fibre properties. As the severity of bleaching conditions increases, the urea-bisulphite solubility remains little changed but the relationships between alkali solubility and cysteic acid (Figure 10.36) and between cystine and cysteic acid (Figure... 

Carbonate removal decreases the adsorption capacity of calcareous soils for trace elements such as Zn (Martinez and Motto, 2000). Solubility curves of the calcareous soil after removal of carbonates resemble those of noncalcareous soils. Solubility values in calcareous soils are within those found for noncalcareous soils. Zinc is completely desorbed after adsorption on pure CaC03 surfaces by lowering the pH of the solution (Zachara et al., 1989). 

The thermodynamic solubility of a drug is the concentration of the compound that is dissolved in aqueous solution in equilibrium with the undissolved amount, when measured at 25°C after an appropriate time period. Aqueous solubility has long been recognized as a key molecular property in pharmaceutical science. Drug delivery, transport and distribution phenomena depend on solubility thus, it is of considerable value to possess information of the solubility value of a drug candidate, to be able to predict the solubility for unknown compounds and, finally, to be able to modify the structure of a compound in order to modulate its solubility value in an appropriate manner. 

However, from our point of view, there remains a lack of sufficiently precise and reliable methods to compute thermodynamic water solubility. The majority of methods work only for congeneric series of compounds, and many have not been developed to function in areas of pharmaceutical research using drug-like molecules. Most of the methods do not use the three-dimensional structure of the compounds, while some depend on previous knowledge of certain experimental properties of the compounds of interest. Moreover, all of the methods are dependent upon the quality of solubility values in the training set used to develop the model indeed, this latter point is a critical limitation that has a major influence on solubility estimations. 

For all these reasons, and despite what is reported in many publications, an acceptable error of 0.5 log unit in predicted solubility value remains an acceptable target. 

The VolSurf approach was used to correlate the 3D molecular descriptors by utilizing the water solubilities for as many compounds as could be found. Although over 2000 solubility values were identified, many showed contradictory results (both low and high values published). Moreover, some of the estimations had not been made by the authors and the original reference was not reported, while others were simply wrong, having not been measured under the standard conditions required. From the 2000 compounds, about 850 were carefully selected in addi-... 

The average error in the external prediction was about +0.8 log unit. Although this range was still not suitable to predict the precise solubility values of external compounds, it was sufficient to rank compounds in different solubility categories and to use it for the filtering of compounds in virtual databases. 

The solubility parameter of water is 17 or 23, depending on the association structure of water used in the calculation. None of the values listed in Table II are within two units of either value and by the general rules of the solubility concept, none of the polymers in Table II should be water soluble. Homopolymers of monomers c, e, or f in Figure 3 are not water soluble. The solubility values listed for the W-SPs studied do not correlate with the equilibrium pressures observed. A general correlation is noted if the values of the most hydrophobic segments (i.e., the oxypropyl, oxybutyl and acetate) are compared with PMVE. The... 

Processing stresses increase the (metastable) solubility by causing relatively small increases, represented by 8, in the Gibbs free energy. This increase in free energy, 8G, is related to the measured solubility values, Cs, according to... 

The concept of metastable solubility values is recognized by scientists familiar with processed (stressed) solids, but it is not well known to scientists accustomed to highly crystalline materials. Because of the relative sensitivity of... 

Aqueous solubility values for the samples analyzed compared favorably with results obtained by traditional methods. The solubility values for amiodarone HC1, reserpine, and benzanthrone were lower than the LOQ of the, uPLC system used for the evaluation. Results of the evaluation of compound solubility employing no-filtration /iPLC were compared with those obtained by two traditional methods (1) multiscreen filtration followed by a UV plate reader, and (2) the shake flask method followed by a UV plate reader. As shown in Figure 6.31, the solubility values determined by the different methods are comparable for most compounds examined. Figure 6.32 shows the results of evaluations of aqueous solubility at four different pH levels for phenazopyridine and piroxicam samples. 

FIGURE 6.32 Solubility values at different pH values for phenazopyridine and piroxicam samples obtained with a Nanostream PLC system (error bars represent + one standard deviation). Values are compared with reported values. Literature values adapted from cited manuscripts. 

Dissolution indicates the rate-limiting step for compound absorption when drugs are administered orally. The solubility of a pharmaceutical compound represents its maximum concentration in an aqueous buffer. Additional compound will not dissolve above this concentration. The solubility value is often heavily dependent upon pH and temperature and is typically measured at physiologically important pH levels and body temperature. The standards for dissolution testing are determined by the United States Pharmacopoeia (USP). Testing typically requires sampling of a solution at 15, 30, 45, and 60 min for immediate-release products. /./Pl.C is ideally suited for use in conjunction with USP apparatus types I or II and can rapidly analyze multiple time points or replicate samples. 

The in vitro estimate of potential availability was defined, somewhat arbitrarily, as calcium solubility (18,000 x g supernatant) after complete digestion. Potentially available calcium was expressed as a percentage of the total food calcium (Figure 1). With the exception of a low in vitro calcium solubility value for whole milk, our earlier data compared reasonably well with calcium bioavailability information in the literature (7.) ... 

Table 9 Correlated Solubility Values From SoluCalc...

The solubility values are functions of pure component properties of the solute (a// /uv, 7ffl ) and the liquid phase activity coefficients of the components in solution. Solubility is calculated using the following equation... 

Two recent events allow a more detailed picture of the solubility of hydrogen, nitrogen, oxygen, and the noble gases in water to be given, than could have been given even a year ago. First, a careful compilation and evaluation of the gas solubility values in water at a gas partial pressure of one atm between the temperatures of 273.15 and about 350 K was carried out by Battino [1 —5]. Second, an experimental study of the solubility of the noble gases in water at moderate pressures and at temperatures up to 561 K by a new method was reported by Potter and Clynne [6J. 

The estimation of the solubility at one atmosphere gas pressure was made by one of two procedures. If the solubility was measured at only one pressure at a given temperature, Henry s law was used, and the inverse of Henry s constant was calculated as X2(1 atm) = 1/H2 i = X2/P2. The procedure works well at moderate gas partial pressures, but at higher gas partial pressures of 25 atm or more the procedure often appears to give low solubility values. However, it is the only practical procedure when the solubility was measured at only one pressure. When solubility values were measured at several pressures at a given temperature, the data were fitted by a linear regression to an empirical function X2/P2 = a + bP2 to obtain the unit pressure solubility value. In some cases a quadratic rather than a linear function of pressure was used. 

Figures 2 to 9 show the solubility values used in the linear regressions and three curves. The curves were calculated from Battino s recommended equation for data between 273-350 K (solid line ), the tentative three constant equa-...

Helium + water. Battino selected solubility data from nine papers for the 273-348 K region (1). We have added values calculated from the data of Potter and Clynne ( ) and from Wiebe and Gaddy (7). The solubility value which was calculated from the data of Wiebe and Gaddy at 590 K, was not used in the linear regression. The data and curve are shown in Figure 2. Only one curve is shown. Battino s recommended equation for the solubility data below 348 K and the equation for the entire data set differ by only a fraction of a percent. The curve for the four constant equation is not shown. 

Sisskind and Kasarnowsky (8) measured one high pressure solubility value for the system at 273 K. 

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