Corticosteroid水溶性誘導体の製剤学的研究(第2報) : 水溶液中におけるHydrocortisone 21-Aminoalkylcarboxylate類の安定性

概要

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Eleven kinds of water-soluble hydrocortisone 21-aminoalkylcarboxylates were synthesized and their apparent pK_a values were measured. Kinetic examinations were made on the behavior of these derivatives to hydrolysis reaction in an acid aqueous solution. These derivatives were found to undergo hydrolysis by the first-order reaction. At pH 3.0 and 100°, there was a correlation (r=-0.883) between the logarithm of the decomposition rate constant of these derivatives and their apparent pK_a value, and it was assumed that pK_a values had a more important effect on stability than their steric effect. Comparison of pH profiles of the decomposition rate constant in the range of pH 1-5 indicated two kinds of pattern according to the chemical structure of the substituents. It was assumed that these derivatives were decomposed by the catalytic effect of the hydroxyl ion in the range above pH 3. Examinations were also made on the effect of ionic strength, temperature, and buffer on the decomposition rate constant of several of these derivatives.
1971-08-25