Physicochemical properties of amphoteric β‐lactam antibiotics I: Stability, solubility, and dissolution behavior of amino penicillins as a function of pH

The degradation rate, solubility, and dissolution rate of amino penicillins, amoxicillin, ampicillin, epicillin, and cyclacillin, were determined quantitatively as a function of pH. In the pH range studied, 0.30‐10.50, the degradation of amoxicillin and epicillin followed pseudo‐first‐order kinetics to give the same type of pH‐rate profiles as those of ampicillin and cyclacillin. Cyclacillin anhydrate was the most soluble, followed in order by ampicillin anhydrate, ampicillin trihydrate, amoxicillin trihydrate, and epicillin anhydrate. These pH‐solubility profiles showed U‐shaped curves. The dissolution rate constants from the rotating disk were analyzed by the simultaneous chemical reaction and diffusion models. Their relative bioavailability after a single oral administration was assessed from their physicochemical properties determined in vitro.