The Stability Study of Cefepime Hydrochloride in Various Drug Combinations

Abstract

Modern antibiotics face many obstacles, starting with the ever-increasing resistance of microorganisms directed against the antibiotic. An important problem is also the existing trend of polypharmacy. The aim of this study was to develop qualitative and quantitative conditions for the determination of cefepime-hydrochloride solution individually and in mixtures containing other substances with biological activity, such as ketoprofen, gestodene with ethinylestradiol, estradiol, caffeine, calcium ions, paracetamol, bisoprolol, acetylsalicylic acid and ibuprofen, using thin-layer chromatography combined with densitometric analysis. The influence of temperature on the stability of cefepime in these situations was investigated. Furthermore, the effect of UV radiation on the stability of the antibiotic in model drug mixtures was tested. On the basis of the dependence of changes on the concentration of cefepime over time, the order of the reaction was designated, followed by the kinetic parameters of the reactions. Statistical analysis proved that the rate-of-concentration changes in the analyzed conditions corresponded to first-order kinetics. In the course of optimizing the analytical procedure, taking into account the lack of interference of the main peak with the additional peaks and the retardation factor (RF), the mobile phase with the composition of ethanol: 2-propanol: acetone: water (4:4:1:3, v/v/v/v) was selected, while silica gel 60F254 TLC plates were used as the stationary phase. Cefepime-peak areas obtained during the analysis at the analyzed time points allowed us to conclude that the stability of the antibiotic decreased with increasing temperature. The greatest stability was obtained in mixtures with calcium ions (half-life values (t0.5) up to 1320.00 h), while the greatest degradation occurred in combination with hormones (t0.5, 2.00 h at 40 °C). Studies have also demonstrated the destructive UV-radiation impact on the stability of these antibiotic-drug combinations (t0.5, 0.23–0.71 h).