Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of Glimepiride-Captisol Inclusion Complexes

Arpita Pal; Sudeep Roy; Akhil Kumar; Syed Mahmood; Nasrin Khodapanah; Sabu Thomas; Christian Agatemor; Kajal Ghosal

doi:10.1021/acsomega.0c01228

Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of Glimepiride-Captisol Inclusion Complexes

ACS Omega. 2020 Aug 4;5(32):19968-19977. doi: 10.1021/acsomega.0c01228. eCollection 2020 Aug 18.

Authors

Arpita Pal¹, Sudeep Roy², Akhil Kumar³, Syed Mahmood^{4

5}, Nasrin Khodapanah⁶, Sabu Thomas⁷, Christian Agatemor⁸, Kajal Ghosal¹

Affiliations

¹ Dr. B. C. Roy College of Pharmacy and AHS, Durgapur 713206, India.
² Department of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, 61600 Brno, Czech Republic.
³ Department of Biotechnology, CSIR-CIMAP Kukrail Picnic Spot, Lucknow 226015, India.
⁴ Department of Pharmaceutical Engineering, Faculty of Chemical and Process Engineering Technology, University Malaysia Pahang, Gambang 26300, Malaysia.
⁵ Centre of Excellence for Advanced Research in Fluid Flow (CARIFF), University Malaysia Pahang, Gambang 26300, Malaysia.
⁶ Faculty of Engineering Technology, University Malaysia Pahang, Gambang 26300, Malaysia.
⁷ International and Inter-University Center for Nanoscience and Nanotechnology (IIUCNN), Mahatma Gandhi University, Priyadarshini Hill, Kottayam 686560, Kerala, India.
⁸ Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore 21231, United States.

Abstract

This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepiride-Captisol 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 glimepiride-Captisol complex showed an A_L-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 glimepiride-Captisol complex was higher in distilled water of pH ∼6.0 than in phosphate buffer of pH 7.2.