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Depicting polymorphism in eutectic mixtures
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DOI：10.1016/j.jics.2024.101489.png)
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The current investigation reveals the presence of polymorphism within linezolid eutectic mixtures containing syringic acid, fumaric acid, and isonicotinamide. Linezolid was combined with the said coformers through cogrinding in 1:1 stoichiometric ratios to produce binary mixtures. Through techniques such as differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy, the eutectic nature of these mixtures was confirmed. Polymorphism was identified further through the emergence of an exothermic event positioned between the two melting endotherms in DSC thermograms. This endoexo-endo transition signifies the thermally-induced polymorphic transformation occurring within the eutectic mixtures. The observed behavior was validated through real-time visual analysis using hot-stage microscopy analysis (HSM). Utilizing PXRD data, quantitative phase analysis (QPA) was employed to determine the weight fractions of individual components in various eutectic polymorphs, yielding reliable outcomes. The morphological characteristics and surface alterations of eutectic polymorphs were scrutinized via scanning electron microscopy (SEM). Moreover, eutectic polymorphs formed by the combination of linezolid and isonicotinamide demonstrated fivefold increase in aqueous solubility and a fourfold faster intrinsic dissolution rate (IDR) compared to marketed linezolid.
Keyword:
Eutectics
Polymorphism
Solubility
Intrinsic dissolution rate
Linezolid
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