Effect of initial concentration on stability of panipenem in aqueous solution.
The effect of initial panipenem (CAS No. 87726-17-8) concentration on its degradation in an aqueous solution was investigated. The degradation of panipenem followed pseudo-first-order kinetics at all the pH values tested. However, in an acidic solution, the degradation rate increased with the initial panipenem concentration. On the other hand, in an alkaline solution, the degradation rate was not affected by its initial concentration. In an acidic solution, the plots of the first-order rate constants versus initial panipenem concentrations showed a linear relationship. Theoretically, the first-order rate constant is independent of the initial concentration, and therefore, the results suggested unusualness. We investigated the results obtained under acidic conditions in detail to find a very complex reaction mechanism: panipenem and its degradation products are factors causing the unusual increase in the degradation rate. Moreover, it was shown that the dissociation of the carboxyl group played an important role in the degradation of panipenem.
Ito
Nobuya
N
Pharmaceutical Development Laboratories, SANKYO CO., LTD, Hiratsuka-shi, Kanagawa, Japan. noitou@sankyo.co.jp
Suzuki
Masahiko
M
Kusai
Akira
A
Takayama
Kozo
K
D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012996:Solutions / Q000737:chemistry; D013845:Thienamycins / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D012996:Solutions; D013845:Thienamycins; D014867:Water; C039536:panipenem