Physicochemical properties of amphoteric β‐lactam antibiotics II: Solubility and dissolution behavior of aminocephalosporins as a function of pH

The solubility of aminocephalosporins in aqueous solution at 37° and an ionic strength of 0.5 exhibited U‐shaped curves against pH. At their isoelectric pH, cephradine monohydrate was the most soluble, followed by cephalexin monohydrate and cephaloglycin dihydrate, with intrinsic solubilities of 26.0, 17.2, and 14.8 mg/ml, respectively. The dissolution rate constants from the rotating disk were also determined as a function of the pH of the dissolution medium and interpreted reasonably by the simultaneous dissociation equilibrium reaction and the diffusion kinetics model. Energies for the solubility and dissolution were determined for these three aminocephalosporins.