Measurement For Solubility Of Levofloxacin And Analysis Of Its Eutectic Point

Levofloxacin as the third generation of fluoroquinolone, has been widely used inclinical, because of its broad antibacterial spectrum, strong antibacterial activity, andeasily absorbed by the human body. Asymmetric synthesis is often used to producelevofloxacin in the pharmaceutical industry, in combination with the purification viacrystallization processes. The solubility data in different solvents are fundamental todevelop a crystallization process to purify enantiomeric levofloxacin.The solubility of levofloxacin in pure ethanol,1-propanol,2-propanol,1-butanol,acetic acid and ethyl acetate at temperatures ranging from288.15to328.15K atatmospheric pressure was measured by a balance method. The solubility oflevofloxacin above298K increases in six different solvents as below:2-propanol <ethanol <1-propanol <ethyl acetate <1-butanol <acetic acid. The experimental datawere fitted with the modified Apelblat equation. We further carried out the molecularmodeling to deduce the reason that results in the significant difference of thesesolubilities. The dissolution enthalpy and entropy of levofloxacin were predicted fromthe solubility data. Finally, the solubility data were correlated by two localcomposition models: NRTL1and UNIQUAC.Based on the solubility data of levofloxacin, this topic has determined the eeeuofeutectic point of the (R, S)-ofloxacin/acetic acid system at303.15K and308.15K,and the result showed that the eeeuof eutectic point was92%. For a racemiccompound system with the starting solid ee lower than that of eutectic point, thecomposition of the supernatant will be represented by eutectic point eeeu. For aracemic compound system with the starting solid ee higher than that of eutectic point,the solids will be pure levofloxacin with100%ee.