Ciprofloxacin-Mefenamate Salt Preparation and Quantitative Analysis Using Green Methods
Abstract
Synthetizing a drug multicomponent system is an effective strategy to improve the physicochemical properties of both components. Ciprofloxacin is a BCS IV fluoroquinolone antibiotic with low solubility and permeability. Recently, this antibiotic was reported to form a salt with mefenamic acid using more modern methods and instruments. However, these instruments are still not widely accessible in developing countries. This research purposed to explore and utilize the alternative methods, which were more affordable and green, to analyze the ciprofloxacin-mefenamate salt formation. Next, the solubility of mefenamic acid in the antibiotic-antiinflammatory salt was investigated. Firstly, the multicomponent system was prepared by SDG using ethanol 98%, and the product was confirmed using PXRD, compared to the reported phase. The thermal profile was conducted using a simple melting point determination using electrothermal measurement. Next, FTIR was done to detect the salt formation, and the NMR solution also investigated the interaction in the solution phase. Another green quantitative method, spectrophotometry derivative, was developed for the solubility test performance, replacing HPLC. The results showed that the electrothermal data are similar to previously reported DSC data. Next, FTIR clearly identified the ionic interactions forming the salt through significant changes in specific bands and peak appearances, as well as NMR that may show the interaction in the solution phase. After that, the UV derivative methods were developed and validated with reliable parameters for simultaneously determining ciprofloxacin and mefenamic acid levels. The ciprofloxacin solubility increased twofold, comparable with the reported data from HPLC analysis. Meanwhile, new data showed a threefold increase in mefenamic acid solubility compared to its single component. Hence, the economist electrothermal tool, FTIR, and NMR methods effectively identified the ionic interactions in ciprofloxacin-mefenamate, which were predicted to remain stable in solution and have the potential for further development.
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