Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of GlimepirideCaptisol Inclusion Complexes

This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepirideCaptisol complexes of different mass ratios (1:1, 1:2, and 1:3 w/w) by a physical mixing or freeze-drying technique, and found that complexation with Captisol enhanced the water solubility of glimepiride. Molecular docking and dynamic simulation predicted complex formation; at the same time, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscope indicated molecular interactions that support complexation. We also found that an inclusion complex was better than a physical mixture in enhancing the complexation of glimepiride with Captisol and enhancing water solubility. Phase solubility study of the glimepirideCaptisol complex showed an AL-type profile, implying the formation of a 1:1 inclusion complex. The study also revealed that pH influenced the stability of the complex because the stability constant of the glimepirideCaptisol complex was higher in distilled water of pH 6.0 than in phosphate buffer of pH 7.2.

Keywords

Glimepiride, Captisol, molecular docking, molecular simulation

Citation

ACS OMEGA. 2020, vol. 5, issue 32, p. 19968-19977.
https://pubs.acs.org/doi/10.1021/acsomega.0c01228

Document type

Peer-reviewed

Document version

Published version

Language of document

en

Document licence

(C) American Chemical Society