New Organic Salt from Levofloxacin-Citric Acid: What Is the Impact on the Stability and Antibiotic Potency?

Abstract

This research dealt with the composition, structure determination, stability, and antibiotic potency of a novel organic salt composed of levofloxacin (LF) and citric acid (CA), named levofloxacin-citrate (LC). After a stoichiometric proportion screening, the antibiotic-antioxidant reaction was conducted by slow and fast evaporation methods. A series of characterizations using thermal analysis, powder X-ray diffractometry, vibrational spectroscopy, and nuclear magnetic resonance confirmed LC formation. The new organic salt showed a distinct thermogram and diffractogram. Next, Fourier transform infrared indicated the change in N-methylamine and carboxylic stretching, confirmed by 1H nuclear magnetic resonance spectra to elucidate the 2D structure. Finally, single-crystal diffractometry determined LC as a new salt structure three-dimensionally. The attributive improvements were demonstrated on the stability toward the humidity and lighting of LC compared to LF alone. Moreover, the antibiotic potency of LF against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) enhanced ~1.5–2-fold by LC. Hereafter, LC is a potential salt antibiotic-antioxidant combination for dosage formulas development.

Stability and Antibiotic Potency Improvement of Levofloxacin by Producing New Salts with 2,6- and 3,5-Dihydroxybenzoic Acid and Their Comprehensive Structural Study

“…Based on the “W” profile of the phase diagrams in Figure 1 , the formation of the LF–DHBA multicomponent system occurred in the (1:1) molar ratio, which is shown by the melting point between the two eutectic points. This stoichiometric ratio was also found in the reaction of LF with other organic compounds, namely, phthalimide [ 21 ], caffeic acid [ 21 ], and citric acid [ 24 ].…”

“…LF’s thermogram at the bottom of the figure shows endothermic peaks at 117 °C and 225 °C. This profile indicates a hemihydrate form of LF; the first curve represents the breaking point of the water molecules, while the second curve is LF’s melting point [ 24 ]. The thermogram demonstrated 166 °C as the melting point of 2,6-DHBA and 237 °C as that of 3,5-DHBA, which agrees with past research [ 43 , 44 ], confirming their identity and purity.…”

“…In addition, the combination of LF with phthalimide and caffeic acid has recently been reported to increase potency [ 21 ], as have other antibiotic solid multicomponent systems, such as azithromycin with paracetamol [ 22 ] and cefixime [ 23 ]. Furthermore, we recently found that salt from LF with the antioxidant citric acid can improve stability and increase potency two-fold [ 24 ].…”

“…The pKa values of 2,6-DHBA and 3,5-DHBA at 25 °C are 1.30 [ 30 ] and 4.04 [ 31 ], respectively. By contrast, LF is a zwitterion compound with two pKa values at 25 °C: 5.35 (carboxylic acid) and 6.72 (piperazinyl ring) [ 24 ]. Different pH values may facilitate the multicomponent formation between LF and benzoic acid derivates.…”

“…Moreover, microbial tests are conducted to investigate antibiotic potency improvement. These findings may enrich the scientific information in the chemistry and pharmaceutical fields to strengthen solid-state arrangement as a strategy for antibiotic development, including the development of LF [ 19 , 20 , 21 , 22 , 23 , 24 ].…”