The Formation of β-Cyclodextrin Complexes with Levofloxacin and Ceftriaxone as an Approach to the Regulation of Drugs’ Pharmacokinetic

The study has been devoted to the complexation of hydroxypropyl-β-cyclodextrin (HPCD) with antibacterial drugs, namely, ceftriaxone (CT) and levofloxacin (LV), which are used to treat respiratory diseases, including bacterial infections of the respiratory tract. FTIR and NMR spectroscopic investigations have shown that the LV–HPCD complex is formed mainly due to the inclusion of the aromatic fragment of LV into the HPCD cavity; while the CT–HPCD complex is realized on the HPCD surface. Being a more hydrophobic molecule, LV forms ten times stronger complexes with HPCD than does CT: K(disLV-HPCD) ~ 10(–3) M, while K(disCT-HPCD) ~10(–2) M at pH 7.4. It has been shown that, for singly charged forms of the drugs, the complexes are two times more stable. Fluorescence spectroscopy has been employed to study the thermodynamic parameters for the interaction of dosage forms with human serum albumin. Negative values of ΔH and ΔS of the reaction have indicated both hydrogen bonding and van der Waals interactions during the complexation of both drugs with human serum albumin. It has been found that the protein is ~4 times more strongly bound to LV at 37°C as compared with CT. The data obtained will make it possible to improve the characteristics of the studied drugs and bring the methods of treating severe forms of respiratory diseases to a new level.