Depicting polymorphism in eutectic mixtures

Abstract Objective The present investigation unveils the existence of polymorphism in eutectic mixtures of linezolid with syringic acid, fumaric acid and isonicotinamide. This is a first of its kind study confirming polymorphism in binary mixtures. Methods Binary mixtures of linezolid with different coformers were obtained by co-grounding in 1:1 stiochiometeric ratios and their eutectic nature was established by DSC, FTIR and powder XRD. The polymorphism within these eutectic mixtures was characterized by endo-exo-endo trio in their DSC thermograms; further confirmed using HSM, QPA, SEM and NMR analytical techniques. Solubility and intrinsic dissolution rate were also ascertained for the prepared polymorphic eutectics and compared with the pure drug. Results Polymorphism was detected by the appearance of an exotherm in between the two melting endotherms in DSC thermogram. This endo-exo-endo trio represent the heat mediated polymorphic transformation within the eutectic mixtures. The behavior was supported by the real time visual HSM. The percentage weight fractions of individual components in different eutectic polymorphs were determined by QPA using powder XRD data and gives reasonable results. The morphology and surface changes of eutectic polymorphs were reviewed by means of SEM. Eutectic polymorphs of linezolid with isonicotinamide (untreated and heat treated polymorphs) exhibits the 5 fold increase in aqueous solubility and 4 times faster intrinsic dissolution rate compared to commercialized linezolid. Conclusion This study reveals the existence polymorphism in linezolid eutectic mixtures having higher solubility could prove to be promising in pre-formulation.