Characterization and Molecular Modelling of Cyclodextrin/Fluoroquinolone Inclusion Complexes

Background: Cyclodextrins are widely used as complexing agents to increase the solubility of poorly water-soluble drugs, to improve their bioavailability and stability, to reduce or prevent gastrointestinal or ocular irritation, to reduce or eliminate unpleasant smells or tastes and to prevent drug-drug or drug-additive interactions. In recent years, cyclodextrins have been proven to be effective as host compounds in molecular recognition and chiral separation.
Aim: To evaluate the complexation role of cyclodextrins toward fluoroquinolones (FQ) in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as chiral selectors in case of racemic mixture compounds.
Material and methods: Guest-host interactions of three second generation quinolones, ciprofloxacin, ofloxacin and norfloxacin with two parent cyclodextrins, beta-cyclodextrin (b-CD), gamma-cyclodextrin (g-CD) and a beta-cyclodextrin derivative, 2-hydroxypropyl beta-cyclodextrin (HP-b -CD), were tested. Computer aided molecular modelling (ChemBio3D Ultra 12.0) was utilized to predict the preferred orientation of fluoroquinolones in the cyclodextrin cavity and the main structural features responsible for the enhancement of their solubility and photostability. Ciprofloxacin/b-cyclodextrin complex was prepared and the formation of inclusion complex was
demostrated by IR spectroscopy.
Results: Our studies show that the orientation with the piperazinyl group included in the CD cavity is energetically more favorable.
Conclusions: The CDs act as complexing agents with the three FQ derivatives, which enter inside the CD torus, and interact with the hydroxyl groups of CD by Van der Waals, electrostatic forces ang hydrogen bonding. Our results suggest the 1:1 stoichiometry in the complex formation.