The present study was conducted to assess the solubility of levofloxacin and ofloxacin in different mono- and mixed solvent systems at different temperatures to provide an experimental basis for the preparation of levofloxacin and ofloxacin nanosuspensions. To this end, the solubility of both compounds was evaluated using a solid–liquid equilibrium technique in DMSO, acetone, ethanol, NMP, and water monosolvents and ethanol–water mixed solvents at different volume fractions and temperatures. The modified versions of the van’t Hoff and Gibbs equations were recruited to calculate the thermodynamic properties of the solutions. The correlation between the solubility data of levofloxacin and ofloxacin and different mathematical models, including the Yalkowsky, Jouyban-Acree, and van’t Hoff models and their combinations was studied. According to the results, the highest and lowest solubility of levofloxacin and ofloxacin were attainable in 1 (pure ethanol monosolvent) and 0.1 v/v of ethanol fractions in ethanol/water mixed solvent. Moreover, the solubility of both compounds was superior at higher temperatures. Afterwards, the nanosuspensions were prepared using the solvent-antisolvent method. Different characterization techniques revealed the formation of the smallest particles with relatively irregular morphology in the 0.1 v/v volume fraction of ethanol in water. The XRD analysis exhibited the typical crystalline diffractions of levofloxacin and ofloxacin and the thermal transitions and stability of both compounds were investigated using DSC and TGA techniques. The results obtained in this study could be used to enhance the solubility and bioavailability of levofloxacin and ofloxacin during the drug formulation development and manufacturing processes.
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