Physicochemical Properties of Amphoteric β-Lactam Antibiotics. III. Stability, Solubility, and Dissolution Behavior of Cefatrizine and Cefadroxil as a Function of pH

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A quantitative study on the pH-dependency of the degradation, solubility, and dissolution of fatrizine and cefadroxil was carried out at 35 or 37℃, and at an ionic strength of 0.5. The gradation rates of cefatrizine were determined by high-performance liquid chromatography. At constant pH and temperature, the degradation followed pseudo first-order kinetics. The shape of the rate constant-pH profile resembled those for cefadroxil and other aminocephalosporins. In and acidic medium below pH 4,cefatrizine was reasonably stable with a half-life of 14d at 35℃. At neutral pH, cefatrizine was degraded with a half-life of about 6h at 35℃ via intramolecular reaction by the nucleophilic attack of the α-amino group on the β-lactam moiety. The intramolecular reaction rate was very similar to that of cephaloglycin, but ten times faster than those for cefadroxil, cephalexin, and cefradine under the same conditions. Both aminocephalosporins exhibited similar U-shaped solubility curves against pH. Their minimum solubilities were 4.6×10^<-2>M, close to that of cephalexin monohydrate. The dissolution rate constants from a rotating disk were determined and interpreted successfully in terms of the dissociation equilibrium reaction and the diffusion kinetic model. Temperature effects on the degradation rate, solubility, and the dissolution rate were also examined.
社団法人日本薬学会の論文
1983-11-25