Spectroscopic Analysis and Dissolution Properties Study of Tosufloxacin Tosylate/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Prepared by Solution-Enhanced Dispersion with Supercritical CO2

Abstract

The aim of this study was to prepare tosufloxacin tosylate (TFLX) and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes by solution-enhanced dispersion with supercritical CO2 (SEDS) and optimize process parameters, in vitro dissolution evaluation, and determination of inclusion sites. The effects of operating pressure, operating temperature, drug concentration, and solution flow rate on the particle size and morphology of the inclusion complex were analyzed by a single factor design experiment. The SEDS-prepared inclusion complex was characterized by TG/DSC, XRD, SEM, FT-IR, 1H NMR, 2D-ROESY, and MD and measured for in vitro dissolution, solubility, and antibacterial activity. The optimum drug concentration was 40 mg/mL and pressure 16 MPa, temperature 35 °C, and solution flow rate 1 mL/min; under this condition, the mean particle size of the inclusion complex was 1.91 μm. All characterization results confirmed the formation of an amorphous inclusion complex and the sites where TFLX and HP-β-CD bind through the H-bond were located on the aromatic B ring, pyrrolidine, and naphthyridine ring protons. Furthermore, the solubility of the inclusion complex (489.87 μg/mL) was significantly higher than that of TFLX, and the dissolution rate of TFLX increased from the initial 13.99 to 61.04% in ultrapure water. In vitro study showed that the inclusion complex maintained the antibacterial effect of TFLX. TFLX/HP-β-CD inclusion complex prepared by manipulating SEDS process conditions could significantly improve the dissolution and solubility of the water-insoluble TFLX.