Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents

Formulation characterization and molecular modeling studies

Atul P. Sherje, Vaidehi Kulkarni, Manikanta Murahari, Usha Y. Nayak, Pritesh Bhat, Vasanti Suvarna, Bhushan Dravyakar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of L-arginine (L-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, L-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of L-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with L-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-L-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD. (Graph Presented).

Original languageEnglish
Pages (from-to)1231-1242
Number of pages12
JournalMolecular Pharmaceutics
Volume14
Issue number4
DOIs
Publication statusPublished - 2017

Fingerprint

Etodolac
Solubility
Colorimetry
X-Ray Diffraction
Powders
Fourier Transform Infrared Spectroscopy
Molecular Dynamics Simulation
2-hydroxypropyl-beta-cyclodextrin
Arginine
Anti-Inflammatory Agents

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Sherje, Atul P. ; Kulkarni, Vaidehi ; Murahari, Manikanta ; Nayak, Usha Y. ; Bhat, Pritesh ; Suvarna, Vasanti ; Dravyakar, Bhushan. / Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents : Formulation characterization and molecular modeling studies. In: Molecular Pharmaceutics. 2017 ; Vol. 14, No. 4. pp. 1231-1242.
@article{31dc6399d5c14f0d81de4e2aac360b2d,
title = "Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents: Formulation characterization and molecular modeling studies",
abstract = "The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of L-arginine (L-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, L-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of L-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with L-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-L-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD. (Graph Presented).",
author = "Sherje, {Atul P.} and Vaidehi Kulkarni and Manikanta Murahari and Nayak, {Usha Y.} and Pritesh Bhat and Vasanti Suvarna and Bhushan Dravyakar",
year = "2017",
doi = "10.1021/acs.molpharmaceut.6b01115",
language = "English",
volume = "14",
pages = "1231--1242",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "4",

}

Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents : Formulation characterization and molecular modeling studies. / Sherje, Atul P.; Kulkarni, Vaidehi; Murahari, Manikanta; Nayak, Usha Y.; Bhat, Pritesh; Suvarna, Vasanti; Dravyakar, Bhushan.

In: Molecular Pharmaceutics, Vol. 14, No. 4, 2017, p. 1231-1242.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents

T2 - Formulation characterization and molecular modeling studies

AU - Sherje, Atul P.

AU - Kulkarni, Vaidehi

AU - Murahari, Manikanta

AU - Nayak, Usha Y.

AU - Bhat, Pritesh

AU - Suvarna, Vasanti

AU - Dravyakar, Bhushan

PY - 2017

Y1 - 2017

N2 - The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of L-arginine (L-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, L-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of L-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with L-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-L-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD. (Graph Presented).

AB - The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and to study the effect of L-arginine (L-Arg) as an auxiliary agent on the complexation efficiency of HP-β-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, L-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-β-CD was observed in the presence of L-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with L-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-β-CD-L-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD. (Graph Presented).

UR - http://www.scopus.com/inward/record.url?scp=85019016311&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019016311&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.6b01115

DO - 10.1021/acs.molpharmaceut.6b01115

M3 - Article

VL - 14

SP - 1231

EP - 1242

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 4

ER -