Joseph M. Indelicato

Pharmaceutical Properties of Loracarbef: The Remarkable Solution Stability of an Oral 1-Carba-l-dethiacephalosporin Antibiotic

Loracarbef is an oral 1-carba-l-dethiacephalosporin antibiotic structurally related to cefaclor. Like many β-lactam antibiotics, loracar-bef exists in several hydrated crystalline forms. The pH–solubility profile curve for loracarbef monohydrate is U-shaped, resembling those for other zwitterionic cephalosporins. Loracarbef was found to be much more stable in solution than cefaclor. For example, in pH 7.4 phosphate buffer, loracarbef was unexpectedly found to be 130–150 times more stable than cefaclor and 10–12 times more stable than cephalexin, depending on the phosphate concentration. The pH-stability profile is U-shaped, similar to that of other zwitterionic cephalosporins, and shows maximum stability at the isoelectric point. At any given pH, loracarbef is more stable in solution than any other therapeutically useful cephalosporin. Acetate, borate, citrate, and especially phosphate buffers have catalytic effects on the rate of loracarbef hydrolysis.