New crystalline salt forms of levofloxacin: conformational analysis and attempts towards the crystal structure prediction of the anhydrous form

Structural information on the anhydrous forms of levofloxacin, a broad spectrum fluoroquinolone antibiotic drug, is limited as it readily converts into the more stable hemihydrate form. Obtaining single crystals of the anhydrous form will be a challenge in this situation. Herein, we report six novel carboxylic acid salt forms of levofloxacin and our attempts towards the crystal structure prediction of its anhydrous form. In-depth analysis of various possible conformations of levofloxacin was performed with the help of high level density functional theory calculations. Useful structural insights obtained from crystal structure analysis of two known hydrates and six new salt forms of levofloxacin were utilized to identify the most probable supramolecular synthons. Synthon information obtained from these crystalline forms was used in the re-ranking of computationally generated crystal structures to arrive at a set of most probable crystal structures for the anhydrous form. A comparison of the crystal structures of the two hydrate forms with the predicted anhydrous form of levofloxacin was performed to understand the hydration-dehydration behaviour.