Solid-state stability studies of faropenem based on chromatography, spectroscopy and theoretical analysis.

AIM

The purpose of this study was to investigate the stability of faropenem in solid state.

RESULTS

The kinetic and thermodynamic parameters of degradation of faropenem were studied using an RP-HPLC method while the changes of spectral properties were investigated using derivative UV and FT-IR. Quantum-chemical calculations, based on the density functional theory, were carried out to support the estimation of the intra-ring stresses of faropenem and for theoretical interpretation of the spectra. The degradation of faropenem was a first-order reaction depending on the substrate concentration at an increased relative humidity and in dry air. The dependence ln k = f(1/T) became the ln k = (2.03 ± 3.22) × 10(4)-(9761 ± 3052)(1/T) in dry air and ln k = (1.25 ± 0.22) × 10(5)-(9004 ± 3479)(1/T ) at 90.0% RH. The thermodynamic parameters Ea, ΔH(≠a), and ΔS(≠a) of the degradation of faropenem were calculated. The dependence ln k = f(RH%) assumed the form ln k = (7.58 ± 1.88) × 10(-2) (RH%) - (5.90 ± 3.90) × 10(-8).

CONCLUSIONS

Stability studies of faropenem showed that the fusion of β-lactam and thiazolidine rings reduces the intra-ring stress, leading to a lower susceptibility to degradation in dry air and at increased RH.