Levofloxacin–pimelic acid multicomponent crystal: enhanced stability and biological properties

Levofloxacin (LFX) is a third-generation synthetic fluoroquinolone antibiotic and the L-enantiomer of ofloxacin. In addition to its widespread clinical use as an antibacterial agent, LFX is considered a promising antitumor candidate. However, its practical utility is limited by chemical and physical instability: upon exposure to ambient moisture, LFX readily converts into an unstable hemihydrate, while light exposure in both the solid state and solution leads to degradation into inactive components, resulting in the loss of antibacterial activity. Photodegradation and hemihydrate formation can be effectively prevented through a multicomponent crystal strategy: molecular self-assembly, driven by complementary hydrogen-bond donors and acceptors, reconfigures intermolecular interactions to form a new crystalline phase, thereby modulating solubility, permeability, bioavailability, and stability. In this work, a novel solid form of LFX—a cocrystal with pimelic acid—was developed. The molecular and crystal structures were determined by single-crystal X-ray diffraction (SCXRD), and the material was further characterized using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The cocrystal exhibited enhanced photostability and hydration resistance compared to pristine LFX. Antibacterial activity, evaluated via the serial dilution method against Gram-positive Bacillus subtilis and Gram-negative Escherichia coli, yielded a minimum inhibitory concentration (MIC) of 0.125 µg/mL for both microorganisms. These findings highlight the promise of this cocrystal as a stabilized pharmaceutical form of levofloxacin that maintains full antibacterial efficacy.