Determination of ionization constants

Ionization constants have been determined for D2O solutions of glycine, gkycylglycine, and DL-alanine (Orlov et al, 1967). The constants were calculated from the peak intensities and were found to be 2.7 and 10.0 for glycine 3.5 and 8.5 for glycylglycine and 2.6 and 10.4 for DL-alanine, for the amino and carboxyl groups, respectively. 

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Tam et al. [37-47] developed an impressive generalized method for the determination of ionization constants and molar absorptivity curves of individual species, using diode-array UV spectrophotometry, coupled to an automated pH titrator. Species selection was effected by target factor analysis. Multiprotic compounds with overlapping pK s have been investigated binary mixtures of ionizable compounds have been considered assessment of inicroconstants have been reported. 

Albert, A., Serjeant, E. P. The Determination of Ionization Constants - A Laboratory Manual, 3rd edn., Chapman Hall, New York, 1984. 

Morgan, M. E. Liu, K. Anderson, B. D., Microscale titrimetric and spectrophotometric methods for determination of ionization constants and partition coefficients of new drug candidates, J. Pharm. Sci. 87, 238-245 (1998). 

A. Albert, E. Serjeant (1984). The Determination of Ionization Constants, 3rd ed. London Chapman and Hall. 

A potentiometric method for determination of ionization constants for weak acids and bases in mixed solvents and for determination of solubility product constants in mixed solvents is described. The method utilizes glass electrodes, is rapid and convenient, and gives results in agreement with corresponding values from the literature. After describing the experimental details of the method, we present results of its application to three types of ionization equilibria. These results include a study of the thermodynamics of ionization of acetic acid, benzoic acid, phenol, water, and silver chloride in aqueous mixtures of acetone, tetrahydrofuran, and ethanol. The solvent compositions in these studies were varied from 0 to ca. 70 mass % nonaqueous component, and measurements were made at several temperatures between 10° and 40°C. 

The determination of ionization constants by UV or visible spectrophotometry may be particularly useful for insoluble compounds (Albert and Serjeant, 1984). For many insoluble compounds, a solution with a concentration as low as1%M may still give an analytically useful chromophore. The method depends on the direct determination of the ratio of molecular species (neutral molecule)... 

An evaluation of the effect of pH on the aqueous solubility of a drug substance is an essential component of preformulation research, and such work is usually conducted along with determinations of ionization constants, solubilization mechanisms, and dissolution rates. ° Methods for the determination of the solubility... 

Some methods used in the determination of ionization constants are shown in Table 3.2. Figure 3.1 shows the curve obtained from the titration of a hydrochloride salt with sodium hydroxide. The pKa obtained from this experiment was 7.9. 

A. Albert and E. Seqeant, The Determination of Ionization Constants A Laboratory Manual, 2nd edn.. Chapman and Hall, London, 1971. 

The relative insolubility of chloroBiiazide in most common solvents has made die determination of ionization constants difficult. Several groups have used aqueous potentiometric titration to obtain pJC data, with the general consensus being that pKgi = 6.85 and pXa2 = 9.45."... 

Peeters J, Determination of ionization constants in mixed aqueous solvents of varying composition by a single titration, /. Pharm. Sci., 67,127-129 (1978). 

Peters JJ, Determination of ionization constants in mixed aqueous solvents of varying composition by a single titration, /. Pharm. Sci., 67,127-129 (1978). NB The paper recognizes riie problem of long extrapolations from aqueous-organic solvent mixtures to estimate pXa values of poorly water-soluble substances. No activity corrections were applied. See Cinnarizine for further details. 

A previously described procedure (Albert and Serjeant, 1972) was used for the determination of ionization constants. Its accuracy was checked with an authentic sample of salicylic acid (at 25°), and die result (2.94) was in close agreement with that reported (2.97)."... 

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