Physicochemical Properties of Amphoteric β-Lactam Antibiotics. III.1) Stability, Solubility, and Dissolution Behavior of Cefatrizine and Cefadroxil as a Function of pH

Akira Tsuji, Emi Nakashima, Kazunori Nishide, Yoshiharu Deguchi, Shoichiro Hamano, Tsukinaka Yamana

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A quantitative study on the pH-dependency of the degradation, solubility, and dissolution of cefatrizine and cefadroxil was carried out at 35 or 37 °C, and at an ionic strength of 0.5. The degradation 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 an acidic medium below pH 4, cefatrizine was reasonably stable with a half-life of 14 d at 35 °C. At neutral pH, cefatrizine was degraded with a half-life of about 6h at 35 °C 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 x10-2m, 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.

Original languageEnglish
Pages (from-to)4057-4069
Number of pages13
JournalChemical and Pharmaceutical Bulletin
Volume31
Issue number11
DOIs
Publication statusPublished - 1983 Jan 1

Keywords

  • aminocephalosporin
  • cefatrizine cefadroxil
  • dissolution rate
  • intramolecular reaction
  • pH effect
  • solubility
  • stability
  • temperature effect
  • β-lactam antibiotics

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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