Solid-state stability study of meropenem - solutions based on spectrophotometric analysis

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences
• Computational Chemistry

Background:

• B-Lactam antibiotics are crucial for treating bacterial infections but often suffer from limited oral bioavailability due to chemical instability.
• Developing non-destructive, green analytical methods is vital for assessing the stability of labile drugs like meropenem.
• This study focuses on evaluating changes in meropenem during solid-state stability testing.

Purpose of the Study:

• To develop and validate rapid, reliable analytical methods for solid-state stability studies of meropenem.
• To employ green analytical approaches that minimize solvent use and sample preparation.
• To utilize spectrophotometric techniques supported by quantum-chemical calculations.

Main Methods:

• Solid-state stability study of meropenem.
• Recording UV, FT-IR, and Raman spectra.
• Density-functional theory (DFT/B3LYP) calculations for molecular geometry and vibrational frequencies.
• Analysis of zero-order spectra and their first derivatives to resolve overlapping peaks.
• Determination of molecular electrostatic potential (MEP) and frontier molecular orbitals (FMOs).

Main Results:

• Successful interpretation of FT-IR and Raman spectra for both non-degraded and degraded meropenem samples.
• Developed a method using derivative spectrophotometry to overcome spectral overlap issues.
• Quantum-chemical calculations (DFT) correlated well with experimental spectral data.
• Determined key electronic properties like HOMO-LUMO gap, providing insights into meropenem's reactivity.

Conclusions:

• Spectrophotometric methods, validated by quantum-chemical calculations, are effective for solid-state stability assessment of meropenem.
• The developed analytical approach is time-saving, reliable, and aligns with green chemistry principles.
• These methods offer a promising, environmentally friendly alternative to conventional chromatographic techniques for analyzing labile drugs.