Effect of an ionic liquid on vancomycin crystallization

Abstract

We first developed a vancomycin crystallization process using an ionic liquid (IL) and improved the crystallization efficiency by optimization of crystallization conditions (pH, conductivity, solution of distilled water and IL/acetone ratio, crystallization temperature, IL concentration). We also investigated the effect of major process parameters on crystallization, using an electron microscope, and identified morphology by XRD analysis. Using ILs (1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]), 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm] [PF6])), vancomycin crystals were successfully formed under the optimal crystallization conditions: pH 4.5; conductivity, 10 mS/cm; solution of distilled water and IL/acetone ratio, 1: 3.5 (v/v); crystallization temperature, 10 °C; IL concentration, 20% (v/v). When using an IL ([BMIm][BF4]), the time required for crystallization in the existing crystallization methods (˜24 hr) was dramatically decreased (˜9 hr) and high-quality vancomycin crystals were successfully formed.