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In silico prediction coupled with in vitro experiments and absorption modeling to study the inclusion complex of telmisartan with modified beta-cyclodextrin

  • Abhishek Chandra
  • M. Vivek Ghate
  • K. S. Aithal
  • Shaila A. Lewis
Original Article
  • 107 Downloads

Abstract

Telmisartan (TEL) is a poorly bioavailable antihypertensive drug candidate owing to its low solubility in all the biofluids. The present study is aimed to enhance the solubility of TEL by forming an inclusion complex with sulfobutylether beta-cyclodextrin (SBE-β-CD), discover its mode of inclusion and predict the bioavailability of the prepared complexes. The formation of the inclusion complex is explained based on the hydrogen bond propensities and molecular dynamics simulations. Freeze-drying method was employed for the preparation of inclusion complexes. These complexes were subsequently characterized by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform-infrared spectroscopy. The spatial configuration of the drug inside the cyclodextrin cavity is probed using 1H and 13C NMR. The in silico docking results are in good agreement with the experimental data and reveal that the hydrogen bond is formed as a part of the guest molecule enters from the broader end of the ring and the protons at the interior portion of the molecule interact with the carboxylic acid (–COOH) group of TEL leading to the formation of a hydrogen bond. The phenyl moiety of TEL occupies the central core and forms multiple Van-der-Waals interactions with the glucopyranose units of the SBE-β-CD. The inclusion complex demonstrates significantly higher in vitro dissolution profile as compared with plain TEL. The GastroPlus™ simulation software generated parameters of inclusion complex in comparison to plain TEL show a seven fold increase in Cmax and 18 fold increase in bioavailability.

Keywords

Telmisartan Sulfobutylether beta-cyclodextrin Solubility enhancement Inclusion complexes Molecular modeling GastroPlus™ 

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  2. 2.International Center for Applied SciencesManipal Academy of Higher EducationManipalIndia

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