A potentially simpler approach to measure aqueous pKa of insoluble basic drugs containing amino groups

The aqueous pK values ((w)(w)pK(a)) of several sparingly water-soluble drugs W with amino groups have been calculated from pK values determined in several methanol/water mixtures ((s)(s)pK(a)) by means of the Yasuda-Shedlovsky equation and by a linear equation that relates (w)(w)pK(a) of amino compounds with (s)(s)pK(a) obtained in any particular W S methanol/water mixture. Parameters of this last equation for amino compounds can be easily calculated from solely the methanol content of the solvent. Results from both approaches are consistent. However, Yasuda-Shedlovsky equation requires several (s)(s)pK(a) determinations in solutions with different methanol content and can be used only from measurements in solutions with a maximum methanol content of about 65% in weight. In contrast, the linear proposed equation allows a very good estimation of (w)(w)pK(a) from only W one experimental (s)(s)pK(a) value, and it permits this estimation from (s)(s)pK(a) determined in a s s solution very rich in methanol. Therefore, it is suitable for very insoluble compounds. The examined amino compounds cover a wide range of (w)(w)pK(a), from 6.7 to 10.6, which have W been estimated from experimental (s)(s)pK(a) values in the whole composition range. In all s instances consistent and satisfactory results have been achieved.