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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

TFLX/HP-β-CD inclusion complex prepared by manipulating SEDS process conditions could significantly improve the dissolution and solubility of the water-insoluble TFLX.

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Abbreviations

TFLX:

Tosufloxacin tosylate

HP-β-CD:

Hydroxypropyl-β-cyclodextrin

CDs:

Cyclodextrins

DMF:

N,N-dimethylformamide

EtOH:

Ethanol

MeOH:

Methanol

SEDS:

Solution-enhanced dispersion by supercritical fluids

SEM:

Scanning electron microscopy

TG/DSC:

Thermogravimetric/differential scanning calorimetry

XRD:

X-ray diffractometry

FT-IR:

Fourier transform infrared spectroscopy

1H NMR and 2D ROESY:

1H nuclear magnetic resonance and 2D rotating-frame Overhauser effect spectroscopy

MD:

Molecular docking simulations

S. aureus :

Staphylococcus aureus

E. coli :

Escherichia coli

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Acknowledgments

The authors are very grateful to the National Natural Science Foundation of China (Grant No. 21666026) and the Natural Science Foundation of Inner Mongolia (Grant No. 2015MS0204) for their financial support in the experimental work.

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Authors and Affiliations

  1. College of Chemical Engineering, Inner Mongolia Autonomous Region, Inner Mongolia University of Technology, No. 49 Aimin Street, Hohhot, 010051, Inner Mongolia Autonomous Region, China

    Jianfei Sun, Hailong Hong, Ning Zhu, Limin Han & Quanling Suo

  2. Inner Mongolia Engineering Research Center for CO2 Capture and Utilization, Hohhot, 010051, China

    Jianfei Sun, Hailong Hong & Ning Zhu

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  1. Jianfei Sun
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  2. Hailong Hong
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Correspondence to Hailong Hong.

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Sun, J., Hong, H., Zhu, N. et al. Spectroscopic Analysis and Dissolution Properties Study of Tosufloxacin Tosylate/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Prepared by Solution-Enhanced Dispersion with Supercritical CO2. J Pharm Innov 15, 603–616 (2020). https://doi.org/10.1007/s12247-019-09405-4

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