Kinetic and thermodynamic analysis of degradation of doripenem in the solid state

Abstract

The kinetic and thermodynamic parameters of degradation of doripenem were studied using a high-performance liquid chromatography method. In dry air, the degradation of doripenem was a first-order reaction depending on the substrate concentration. At increased relative air humidity, doripenem was degraded according to the autocatalysis kinetic model. The dependence ln k = f(1/T ) was described by the equations ln k = 5.10 ± 13.06 − (7576 ± 4939)(1/T ) in dry air and ln k = 46.70 ± 22.44 − (19,959 ± 8031)(1/T ) at 76.4% relative humidity (RH). The thermodynamic parameters E a , H =a , and S =a of the degradation of doripenem were calculated. The dependence ln k = f (RH%) was described by the equation ln k = (0.155 ± 0.077) × 10 −1 (RH%) − (3.45 ± 21.8) ×

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

“…For oxidative media, second‐order kinetics was verified in both concentrations of the agent. In a recent work, the solid state of doripenem was investigated with a focus on stability and degradation kinetics, testing different temperatures (70–120°C) and relative humidity (0, 50, 66, 76 and 90%; Cielecka‐Piontek, Jelinska, Dolhan, & Zalewski, ). In dry air, the decomposition was a first‐order reaction depending on the substrate concentration.…”

Solid-state stability studies of crystal form of tebipenem

“…The observed rate constants of tebipenem degradation in the solid state are listed in Table 1. It was noted that tebipenem degradation products had a catalytic effect, as was the case with other compounds containing 4:5 bicyclic fused rings (doripenem, clavulanic acid) 11,13 . In the chromatograms of degraded samples of tebipenem, decreased peaks of tebipenem were observed while no peak originating from the degradation products appeared 14 .…”

“…Studies into the stability of antibiotics have reported formation of various degradation products and changes in the kinetics of degradation depending on the action of physicochemical factors [4][5][6][7] . Kinetic and thermodynamic analysis of degradation in solutions and in the solid state has been conducted for cabapenems registered for medicinal use [8][9][10][11] . To the best of our knowledge, there have been no reports on the stability of tebipenem.…”

Kinetics of Degradation of Biapenem

“…The kinetic study of biapenem degradation demonstrated that the introduction of a bicyclic thiazolium moiety at C4 of bicyclic 4:5 fused rings improved the stability of biapenem in comparison with some H-and CH 3 -carbapenem analogs [5,[14][15][16]. However, the susceptibility of biapenem to degradation under the influence of stress factors applied in this work is still high and needs to be considered while selecting storage conditions for biapenem preparations and in the process of preparing infusions of those drugs.…”