Thermal decomposition of amorphous beta-lactam antibacterials.

Thermal decomposition rates for amorphous samples of penicillin G potassium, cephalothin sodium, cefamandole sodium, and cefamandole nafate were determined as a function of water content and temperature. Even when rigorously dry, amorphous cephalosporins were at least one order of magnitude less stable than the corresponding unsolvated crystalline form. Absorbed water generally increased both the number of decomposition products and the net decomposition rate. Reaction kinetics were usually apparent first order, but an anomalously high effective reaction order was observed in several systems. Nonlinear Arrhenius plots were observed, and a qualitative model based on molecular relaxation in glayses is proposed. Although decomposition rates at 25 degrees were small for dry samples, even slight decomposition produced visually detectable changes. Thus, the unsolvated crystalline form was noticeably more stable, even at 25 degrees.