Measurements of solubility

Innumerable techniques, of almost infinite variety, have been proposed at one time or another for the measurement of the solubihty of soUds in liquids. No single method can be identified, however, as being generally applicable to all possible types of system. The choice of the most appropriate method for a given case has to be made in the light of the system properties, the availability of apparatus and analytical techniques, the skill and experience of the operators, the precision required, and so on. 

The accuracy required of a solubility measurement depends greatly on the use that is to be made of the information. Requirements vary enormously. In some cases, a simple assessment of whether a substance is highly, moderately or sparingly soluble in a given solvent, with some rough quantification, may be quite sufficient. In others, very high precisions may be demanded. For most work, however, a precision of 1 % should be aimed for, and usually this is not too difficult to attain. 

Extensive reviews of the literature on the subject of experimental solubility determination have been made by Void and Void (1949) and Zimmerman (1952). Purdon and Slater (1946) give an excellent account of the determination of solubility in aqueous salt systems. The monographs of Blasdale (1927) and Teeple (1929) give comprehensive accounts of the problems encountered in measuring equilibria in complex multicomponent aqueous salt systems. 

It is essential that any thermometers, thermocouples, thermistors, etc. used in the thermostat bath and equilibrium cell are accurately calibrated with reference to a standard thermometer. This point cannot be emphasized too strongly. 

Agitation is generally necessary to bring liquid and solid phases into intimate contact and facilitate equilibration. Agitation with a stirrer in an open vessel is not normally recommended, on account of the potential loss of solvent by evaporation, but sealed-agitated vessels are commonly used. Agitation in tightly stoppered vessels, that are rocked, rotated or shaken whilst immersed in a thermostat bath, is also quite a popular method, particularly when many samples have to be tested at the same time. 

Thus at pH values between 3.05 and 7.56 the solution containing 1.4 mg cm- will precipitate. 

A simple turbidimetric method for the determination of the solubility of acids and bases in buffers of different pH can be used. Solutions of the hydrochloride (or other salt) of a basic dmg, or the soluble salt of an acidic compound, are prepared in water over a range of concentrations. Portions of each solution are added to buffers of known pH and the turbidity of the solutions is determined in the visible region. Typical results are shown in Fig. 5.4. Below the solubility limit there is no 

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Figure 15 shows the second virial coefficients derived independently by us and by Reuss and Beenakker66 from the measurements of solubility by Dokoupil, van Soest, and Swenker,18 and the coefficients at room temperature from the conventional measurements of Verschoyle,86 Michels and Wassenaar,49 and Michels and Boer-boom.47 These results are sufficient to give unambiguously the parameters of a 12-6 potential... 

Avdeef, A. High-throughput measurements of solubility profiles. In Pharmacokinetic Optimization in Drug Research Biological, Physicochemical and Computational Strategies, Testa, B., Van de Waterbeemd, H., Folkers, G., Guy, R. (eds.), VHCA, Zurich and Wiley-VCH, Weinheim, 2001, pp 305-325. 

There are numerous experimental complications in the measurement of solubility. Solid phases, formed incipiently, are often metastable with respect to a... 

Solubility and dissolution are processes that take place in the gastric and the luminal fluids, not on the surface of epithelial cells. Measurement of solubility ideally needs to take place at pH 1.7 (stomach) and pH 5-8 (small intestinal tract). Ideally, the screen media should resemble intestinal fluids and contain bile acid-lecithin mixed micelles. Fast and reliable techniques for assessing solubility in... 

When determining the solubility and dissolution rate of amorphous or partially crystalline solids, the metastability of these phases with respect to the highly crystalline solid must be considered. While the low diffusivity of the molecules in the solid state can kinetically stabilize these metastable forms, contact with the solution, for example during measurements of solubility and dissolution rate, or with the vapor, if the solid has an appreciable vapor pressure, may provide a mechanism for mass transfer and crystallization. Less crystalline material dissolves or sublimes whereas more crystalline material crystallizes out. The equilibrium solubility measured will therefore approach that of the highly crystalline solid. The initial dissolution rate of the metastable form tends to reflect its higher... 

Hayashi, M., Sasaki, T. (1956) Measurements of solubilities of sparingly soluble liquids in water and aqueous detergent solutions using nonionic surfactant. Bull. Chem. Soc. Jpn. 29, 857. 

The solubility product as a measure of solubility was introduced in Chapter 3. For the solubility equilibrium... 

There are many ways of expressing the relative amounts of solute(s) and solvent in a particular solution. The terms saturated, unsaturated, and supersaturated discussed above give a qualitative measure of solubility, as do the terms dilute and concentrated. Dilute refers to a solution that has a relatively small amount of solute in comparison to the amount of solvent. Concentrated refers to a solution that has a relatively large amount of solute in comparison to the solvent. These terms are very subjective and chemists prefer to use quantitative... 

Kuramochi, H., Noritomi, H., Hoshino, D., and Nagahama, K. Measurements of solubilities of two amino acids in water and prediction by the UNIFAC model, Biotechnol Prog., 12(3) 371-379, 1996. 

Avdeef A. (2001) High-throughput measurements of solubility profiles,... 

Measurements of solubilities in supercritical CO2 corroborated the hypothesis that the nonpolar character of a series of tetraaUsylammonium dialkyl-dithiocarbamate ion pairs was influenced... 

Lipophilicity is a measure of solubility in nonpolar solvents It is determined from the equilibrium distribution of a drug between water and octanol. 

Complex ions of the type Ag(02CR)J and Ag2(02CR)+ have been proposed to exist in solution, based on measurements of solubility in water and in mixed solvents. Some thermodynamic data for silver carboxylates are given in Table 35.253,254... 

This solubility reflects the conditions that were used. Most solubility measurements (e.g., Regenstein and Regenstein, 1984 Morr et al., 1985) are designed for powders and reflect additional experimental controls. This is a more operational measurement of solubility. 

Equation 3.55 shows that solubility in water depends strongly on the solvatochromic parameters of the solutes. The small standard deviation of 0.137 on a log scale shows that the error of prediction using Equation 3.55 is in the same range as the experimental error in the measurement of solubility (Valvani et al., 1981). Compared with other methods, the LSER approach has resulted in... 

W.A. Collier, D. Janssen and A.L. Hart, Measurement of soluble L-lactate in dairy products using screen-printed sensors in batch mode, Biosens. Bioelectron., 11 (1996) 1041-1049. 

Values of y are most easily obtained from measurements of solubility in water. For a liquid solute in equilibrium with its aqueous solution,... 

For the measurement of solubility the traditional dissolution-equilibrium procedure is employed, i.e., put both the crystals and the mother liquor into a container submerged in a water bath continuously stirred, control the temperature inside the container rigorously at a given value, with the fluctuation no greater than +0.1°C. When the dissolution equilibrium is achieved, measure the concentration of the solute in the liquid phase as the solubility at the temperature given. The equilibrium condition is judged by the criterion that the relative deviation of the values obtained in, at least, three times of adjacent measurements is not greater than %c. 

Seip, H.M., Alstad, J., Carlberg, G.E., Martinsen, K., Skaane, P. (1986) Measurement of solubility of organic compounds in soils. 

There are two separate but interrelated aspects to QSAR modeling of antibacterial peptides the choice of QSAR descriptors and the choice of numerical analysis techniques used to relate these values to antibacterial activity. A simple example of a QSAR descriptor is the total charge of a peptide. A large number of QSAR descriptors is available for small compounds in the literature and from commercial software products that may be considered. A smaller subset is used in QSAR studies of antibacterial peptides and may be separated into two categories descriptors based on empirical values and calculated descriptors. An example of an empirical value is HPLC retention time, which is a surrogate measure of solubility or hydrophilicity/hydrophobicity. An example of a calculated descriptor is total peptide charge at pH 7. 

Rapid hydrolysis — This makes measurement of solubility in water and octanol-water partition coefficient impossible. Consider an example isocyanates have half-lives in water at normal temperatures and pH of a few seconds. There can be no valid reference data for them, nor any practical application of a partition coefficient. That is a clear case others will depend upon the half-life, the intended use of the result, and any validation required. 

Riisbro R, Piironen T, Brunner N, Larsen B, Nielsen HJ, Stephens RW, et al. Measurement of soluble urokinase plasminogen activator receptor in serum. J Clin Ligand Assay 2002 25(l) 53-56. 

The variability of replicate measurements of soluble protein or enzyme activities was investigated by Dehghani et al. [83]. The variability of the assays depended on the measured concentrations and the standard deviation was found to be roughly proportional to the actual values. 

Roveri, A., Maiorino, M., and Ursini, F., 1994, Enzymatic and immunological measurements of soluble and membrane-bound phospholipid-hydroperoxide glutathione peroxidase. Methods Enzymol. 233 202-212... 

Lunn G, Schmuff NR (1997) HPLC Methods for Pharmaceutical Analysis. Wiley-Intersciences, New York Pan L, Ho Q, Tsutsui K et al. (2001) Comparison of chromatographic and spectroscopic methods used to rank compounds for aqueous solubility. I Pharm Sci 90(4) 521-529 PSOL (PION) http //www.pion-inc.com/pSOL.htm Silveston R, Kronberg B (1994) Accurate measurements of solubility and thermodynamic transfer quantities using reversed-phase liquid-liquid chromatography. I Chrom 659(l) 43-56... 

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