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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)47-60
Number of pages14
JournalJournal of Inclusion Phenomena and Macrocyclic Chemistry
Volume91
Issue number1-2
DOIs
Publication statusPublished - 01-06-2018

Fingerprint

beta-cyclodextrin
Computer Simulation
inclusions
prediction
predictions
hydrogen
Hydrogen
bioavailability
Hydrogen bonds
Experiments
hydrogen bonds
plains
Solubility
Biological Availability
solubility
drugs
freeze drying
antihypertensive agents
Molecules
cyclodextrins

All Science Journal Classification (ASJC) codes

  • Food Science
  • Chemistry(all)
  • Condensed Matter Physics

Cite this

@article{c779b7faf03a4a3e8f23cedda9540ac4,
title = "In silico prediction coupled with in vitro experiments and absorption modeling to study the inclusion complex of telmisartan with modified beta-cyclodextrin",
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.",
author = "Abhishek Chandra and Ghate, {M. Vivek} and Aithal, {K. S.} and Lewis, {Shaila A.}",
year = "2018",
month = "6",
day = "1",
doi = "10.1007/s10847-018-0797-x",
language = "English",
volume = "91",
pages = "47--60",
journal = "Journal of Inclusion Phenomena and Macrocyclic Chemistry",
issn = "1388-3127",
publisher = "Kluwer Academic Publishers",
number = "1-2",

}

TY - JOUR

T1 - In silico prediction coupled with in vitro experiments and absorption modeling to study the inclusion complex of telmisartan with modified beta-cyclodextrin

AU - Chandra, Abhishek

AU - Ghate, M. Vivek

AU - Aithal, K. S.

AU - Lewis, Shaila A.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85046655026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046655026&partnerID=8YFLogxK

U2 - 10.1007/s10847-018-0797-x

DO - 10.1007/s10847-018-0797-x

M3 - Article

VL - 91

SP - 47

EP - 60

JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry

JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry

SN - 1388-3127

IS - 1-2

ER -