Stability of cefepime dihydrochloride monohydrate in solid state

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Cefepime is a crucial fourth-generation cephalosporin antibiotic.
• Understanding the solid-state stability of cefepime is vital for its formulation and shelf-life.
• Environmental factors, particularly humidity, can significantly influence drug degradation.

Purpose of the Study:

• To determine the pseudo-first-order rate constants for cefepime decomposition.
• To calculate thermodynamic parameters governing cefepime degradation.
• To investigate the effect of relative humidity on cefepime dihydrochloride monohydrate stability.

Main Methods:

• Solid-state decomposition studies of cefepime dihydrochloride monohydrate were conducted.
• Experiments were performed at 358 K across a relative humidity range of 25.0% to 76.4%.
• Pseudo-first-order kinetics and thermodynamic parameters were calculated.

Main Results:

• The study calculated pseudo-first-order rate constants and thermodynamic parameters for cefepime decomposition.
• A linear relationship was established between the natural logarithm of the rate constant (ln ki) and relative humidity (RH%) at 358 K: ln ki = (0.031 +/- 0.0043) x RH% - 10.08 +/- 0.22.
• Increased relative humidity was found to accelerate the decomposition of cefepime dihydrochloride monohydrate.

Conclusions:

• Humidity is a critical factor affecting the solid-state stability of cefepime dihydrochloride monohydrate.
• The established equation provides a quantitative model to predict cefepime degradation rates under varying humidity conditions.
• These findings are essential for optimizing storage conditions and ensuring the efficacy of cefepime formulations.